610 results on '"Weight Loss genetics"'
Search Results
2. Use of polygenic risk scores to assess weight loss after bariatric surgery: a 5-year follow-up study.
- Author
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Peña E, Mas-Bermejo P, Lecube A, Ciudin A, Arenas C, Simó R, Rigla M, Caixàs A, and Rosa A
- Subjects
- Humans, Female, Male, Follow-Up Studies, Adult, Middle Aged, Gastrectomy methods, Gastrectomy adverse effects, Treatment Outcome, Multifactorial Inheritance, Risk Assessment methods, Bariatric Surgery methods, Genetic Risk Score, Weight Loss genetics, Body Mass Index, Obesity, Morbid surgery, Obesity, Morbid genetics, Gastric Bypass methods, Gastric Bypass adverse effects
- Abstract
Background: Bariatric surgery (BS) is currently the most effective long-term treatment of severe obesity. However, the interindividual variability observed in surgical outcomes suggests a moderating effect of several factors, including individual genetic background. This study aimed to investigate the contribution of the genetic architecture of body mass index (BMI) to the variability in weight loss outcomes after BS., Methods: A total of 106 patients with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy were followed up for 5 years. Changes in BMI (BMIchange) and percentage of total weight loss (%TWL) were evaluated during the postoperative period. Polygenic risk scores (PRSs), including 50 genetic variants, were calculated for each participant to determine their genetic risk of high BMI based on a previous genome-wide association study. Generalized estimating equation models were used to study the role of the individual's polygenic score and other factors on BMIchange and %TWL in the long term after surgery., Results: This study found an effect of the polygenic score on %TWL and BMIchange, in which patients with lower scores had better outcomes after surgery than those with higher scores. Furthermore, when analyzing only patients who underwent RYGB, the results were replicated, showing greater weight loss after surgery for patients with lower polygenic scores., Discussion: Our results indicate that genetic background assessed with PRSs, along with other individual factors, such as biological sex, age, and preoperative BMI, has an effect on BS outcomes and could represent a useful tool for estimating surgical outcomes in advance., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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3. Genetic risk score based on obesity-related genes and progression in weight loss after bariatric surgery: a 60-month follow-up study.
- Author
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Mas-Bermejo P, Azcona-Granada N, Peña E, Lecube A, Ciudin A, Simó R, Luna A, Rigla M, Arenas C, Caixàs A, and Rosa A
- Subjects
- Humans, Female, Male, Adult, Follow-Up Studies, Middle Aged, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Bariatric Surgery, Receptor, Melanocortin, Type 4 genetics, Leptin genetics, Receptors, Leptin genetics, Gastric Bypass, Genetic Predisposition to Disease, Body Mass Index, Polymorphism, Single Nucleotide genetics, Genetic Risk Score, Weight Loss genetics, Obesity, Morbid genetics, Obesity, Morbid surgery
- Abstract
Background: Obesity is a polygenic multifactorial disease. Recent genome-wide association studies have identified several common loci associated with obesity-related phenotypes. Bariatric surgery (BS) is the most effective long-term treatment for patients with severe obesity. The huge variability in BS outcomes between patients suggests a moderating effect of several factors, including the genetic architecture of the patients., Objective: To examine the role of a genetic risk score (GRS) based on 7 polymorphisms in 5 obesity-candidate genes (FTO, MC4R, SIRT1, LEP, and LEPR) on weight loss after BS., Setting: University hospital in Spain., Methods: We evaluated a cohort of 104 patients with severe obesity submitted to BS (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for >60 months (lost to follow-up, 19.23%). A GRS was calculated for each patient, considering the number of carried risk alleles for the analyzed genes. During the postoperative period, the percentage of excess weight loss total weight loss and changes in body mass index were evaluated. Generalized estimating equation models were used for the prospective analysis of the variation of these variables in relation to the GRS., Results: The longitudinal model showed a significant effect of the GRS on the percentage of excess weight loss (P = 1.5 × 10
-5 ), percentage of total weight loss (P = 3.1 × 10-8 ), and change in body mass index (P = 7.8 × 10-16 ) over time. Individuals with a low GRS seemed to experience better outcomes at 24 and 60 months after surgery than those with a higher GRS., Conclusion: The use of the GRS in considering the polygenic nature of obesity seems to be a useful tool to better understand the outcome of patients with obesity after BS., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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4. Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study.
- Author
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Du Y, Qi L, Borné Y, and Sonestedt E
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- Humans, Male, Female, Middle Aged, Cohort Studies, Young Adult, Adult, Risk Factors, Weight Loss genetics, Sweden epidemiology, Aged, Atrial Fibrillation genetics, Atrial Fibrillation epidemiology, Body Mass Index, Genetic Predisposition to Disease, Weight Gain genetics
- Abstract
Background: Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF., Methods: The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants., Results: During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (P
interaction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02-1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF., Conclusions: Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF., (© 2024. The Author(s).)- Published
- 2024
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5. Survey on Interaction Between Nutrient Status and Selected Polymorphisms in Association with Weight Loss of Patients with Severe Obesity Underwent Bariatric Surgery.
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Cheraghi S, Taheri G, Safari S, Bakhshandeh H, Malek M, Moghimian B, and Mottaghi A
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- Humans, Female, Adult, Male, Case-Control Studies, Middle Aged, Weight Loss genetics, Polymorphism, Single Nucleotide, Obesity, Morbid surgery, Obesity, Morbid genetics, Gastric Bypass, Nutritional Status, Uncoupling Protein 2 genetics
- Abstract
Background: There is little information about the effect of single nucleotide polymorphisms (SNP) and nutritional status and weight loss after bariatric surgery. This study investigated the interactive effect of eight obesity-related SNPs and nutritional status on weight loss after Roux-en-Y gastric bypass (RYGB)., Method: This is a case-control study. After 1-year follow-up, the patients who underwent RYGB were dividing into two groups. The case group consisted of patients who lost more than 50% of their excess body weight (EBW%) 1 year after the surgery. The control group included patients who lost < 50% of EBW at same time frame. Then, the relationship between eight SNPs related to UCP2, FTO, LEPR, GHRL, and NPY genes with weight loss were checked., Results: In this study, 160 patients were recruited. The median of age for case and control group were 43 and 42 respectively. The presence of mutant variant NPYrs16147 had a significant relationship in terms of weight loss between the two groups (P > 0.05). In dominant model, two SNPs, UCP2 rs659366 and UCP2 rs660339, showed protective effect of the vitamin D deficiency., Conclusion: In conclusion, the presence mutant variant of NPYrs16147 is directly related to the incidence of weight loss greater than 50% of EBW. However, it is apparent individual behavioral, dietary, and other factors may have more influence on weight loss among patients underwent RYGB., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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6. FTO variant is associated with changes in BMI, ghrelin, and brain function following bariatric surgery.
- Author
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Li G, Hu Y, Zhang W, Wang J, Sun L, Yu J, Manza P, Volkow ND, Ji G, Wang GJ, and Zhang Y
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- Humans, Female, Adult, Male, Middle Aged, Weight Loss genetics, Obesity surgery, Obesity genetics, Obesity physiopathology, Polymorphism, Single Nucleotide, Obesity, Morbid surgery, Obesity, Morbid genetics, Obesity, Morbid psychology, Bariatric Surgery, Ghrelin genetics, Ghrelin metabolism, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO metabolism, Magnetic Resonance Imaging, Body Mass Index, Brain metabolism, Brain diagnostic imaging
- Abstract
BACKGROUNDA polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than noncarriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery.METHODSResting-state functional magnetic resonance imaging and cue-reactivity functional magnetic resonance imaging with high-/low-caloric food cues were performed before surgery and at 1, 6, and 12 months after surgery to examine brain function in 16 carriers with 1 copy of the rs9939609 A allele (AT) and 26 noncarriers (TT). Behavioral assessments up to 5 years after surgery were also conducted.RESULTSThe AT group relative to the TT group had smaller BMI loss at 12-60 months after surgery and lower resting-state activity in posterior cingulate cortex following laparoscopic sleeve gastrectomy (group-by-time interaction effects). Meanwhile, the AT group relative to the TT group showed greater food cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and insula (group effects). There were negative associations of weight loss with ghrelin and greater activation in DLPFC, DMPFC and insula in the AT but not the TT group.CONCLUSIONThese findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight loss.TRIAL REGISTRATIONChinese Clinical Trial Registry Center, ChiCTR-OOB-15006346.FUNDINGThis work was supported by the National Natural Science Foundation of China (grant nos. 82172023, 82202252, 82302292); National Key R&D Program of China (no. 2022YFC3500603); Natural Science Basic Research Program of Shaanxi (grant nos. 2022JC-44, 2022JQ-622, 2023-JC-QN-0922, 2023-ZDLSF-07); Fundamental Research Funds for the Central Universities (grant nos. ZYTS23188, XJSJ23190, XJS221201, QTZX23093); and the Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse (grant no. Y1AA3009).
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- 2024
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7. The Outcome of Metabolic and Bariatric Surgery in Morbidly Obese Patients with Different Genetic Variants Associated with Obesity: A Systematic Review.
- Author
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Zafirovska M, Zafirovski A, Režen T, and Pintar T
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- Humans, Treatment Outcome, Genetic Variation, Weight Loss genetics, Female, Male, Obesity, Morbid surgery, Obesity, Morbid genetics, Bariatric Surgery
- Abstract
Metabolic and bariatric surgery (MBS) effectively treats obesity and related comorbidities, though individual responses vary. This systematic review examines how genetic variants influence MBS outcomes in morbidly obese patients. A comprehensive search in PubMed, Embase, Medline, and the Cochrane Library identified 1572 studies, with 52 meeting the inclusion criteria. Two reviewers independently filtered and selected studies, including relevant cross-references. Research focused on polymorphisms in genes such as UCP2, UCP3, 5-HT2C, MC4R, FKBP5, FTO, CAT haplotypes, LYPAL-1, PTEN, FABP-2, CNR1, LEP656, LEP223, GLP-1R, APOA-1, APOE, ADIPOQ, IL-6, PGC1a, TM6SF2, MBOAT7, PNPLA3, TCF7L2, ESR1, GHSR, GHRL, CD40L, DIO2, ACSL5, CG, TAS2R38, CD36, OBPIIa, NPY, BDNF, CLOCK, and CAMKK2. Most studies explored associations with post-surgery weight loss, while some examined metabolic, cardiovascular, taste, and eating behavior effects as well. Understanding the role of genetic factors in weight loss and metabolic outcomes post-MBS can help tailor personalized treatment plans for improved efficacy and long-term success. Further research with larger sample sizes and extended follow-up is needed to clarify the effects of many genetic variants on MBS outcomes in morbidly obese patients.
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- 2024
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8. Are weight loss and metabolic outcomes of bariatric surgery influenced by candidate glucocorticoid receptor gene polymorphisms? A prospective study.
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Iqbal Z, Vasan SK, Fachim H, Warner-Levy J, Donn RP, Ammori BJ, Heald AH, Soran H, and Syed AA
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- Humans, Female, Middle Aged, Male, Prospective Studies, Treatment Outcome, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 surgery, Obesity, Morbid surgery, Obesity, Morbid genetics, Obesity, Morbid metabolism, Adult, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Polymorphism, Single Nucleotide, Weight Loss genetics, Bariatric Surgery
- Abstract
Background: Bariatric surgery is the most effective treatment for severe obesity. There can be variation in the degree of weight reduction following bariatric surgery. It is unknown whether single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor locus (GRL) affect postoperative weight loss and metabolic outcomes., Materials/methods: We studied the association between selected candidate SNPs and postoperative weight loss and metabolic outcomes in patients with severe obesity undergoing bariatric surgery. The polymorphisms rs41423247 (Bcl1), rs56149945 (N363S) and rs6189/rs6190 (ER22/23EK) were analysed., Results: The 139 participants included 95 women (68.3%) and had a median (interquartile range) age of 53.0 (46.0-60.0) years and mean (SD) weight of 140.8 (28.8) kg and body mass index of 50.3 (8.6) kg/m2. At baseline, 59 patients had type 2 diabetes (T2D), 60 had hypertension and 35 had obstructive sleep apnoea syndrome treated with continuous positive airway pressure (CPAP). 84 patients (60.4%) underwent gastric bypass and 55 (39.6%) underwent sleeve gastrectomy. There were no significant differences in weight loss, glycated haemoglobin (HbA1c) or lipid profile categorized by genotype status, sex or median age. There was significant weight reduction after bariatric surgery with a postoperative BMI of 34.1 (6.8) kg/m2 at 24 months ( p < 0.001)., Conclusion: While GRL polymorphisms with a known deleterious effect on adipose tissue mass and function may have a small, additive effect on the prevalence of obesity and related metabolic disorders in the population, we suggest that the relatively weak biological influence of these SNPs is readily overcome by bariatric surgery.
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- 2024
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9. The expression of NFAT family genes in subcutaneous adipose tissue before and after weight loss in obese individuals.
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Danowska M, Stefanowicz M, and Strączkowski M
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- Humans, Male, Adult, Female, Middle Aged, Treatment Outcome, Case-Control Studies, Time Factors, NFATC Transcription Factors genetics, NFATC Transcription Factors metabolism, Weight Loss genetics, Obesity genetics, Obesity metabolism, Subcutaneous Fat metabolism, Adipogenesis genetics, Insulin Resistance genetics
- Abstract
Background and Aims: Adipose tissue (AT) serves as a vital energy storage site and plays a pivotal role in metabolic regulation, exhibiting a high response to insulin. Impairment in this response may closely associate with obesity, and NFAT (nuclear factor of activated T cells) family genes may be involved in the process. However, human data linking NFAT and AT remains elusive. The aim of this study was to assess the expression of NFAT family genes and markers of adipogenesis in subcutaneous adipose tissue (SAT) among normal-weight and overweight/obese individuals before and after weight loss, in relation to insulin sensitivity., Methods and Results: The study included 45 participants, 15 normal-weight (control group) and 30 overweight or obese, who underwent a 12-week dietary intervention (DI) program. Before and after the program hyperinsulinemic-euglycemic clamp and SAT biopsy were conducted. Before DI, a positive correlations was observed in the expression of NFATc1, NFATc4, and NFAT5 with insulin sensitivity. The expression of NFAT family genes and markers of adipogenesis in SAT was lower in individuals with overweight or obesity compared to normal-weight. Additionally, a positive correlation was noted between NFAT family genes and adipogenesis markers both before and after weight loss. Following the DI program, there was an increase in the expression of NFATc3, NFATc4, and NFAT5 in SAT., Conclusion: Decreased SAT expression of NFAT genes in obesity is partly reversed in response to weight loss. NFAT genes in SAT are associated with insulin sensitivity and adipogenesis. Registration number for clinical trial: NCT01393210., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
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- 2024
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10. Mutations in the leptin-melanocortin pathway and weight loss after bariatric surgery: a systematic review and meta-analysis.
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Zhang N, Wang H, Ran S, Wang Z, Zhou B, Wang S, Li Z, Liu B, Nie Y, Huang Y, and Meng H
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- Humans, Melanocortins genetics, Obesity, Morbid surgery, Obesity, Morbid genetics, Signal Transduction, Obesity surgery, Obesity genetics, Leptin genetics, Leptin blood, Bariatric Surgery, Weight Loss genetics, Mutation
- Abstract
Objective: The objective of this meta-analysis was to quantify the overall effects of gene mutations in the leptin-melanocortin pathway on short- and long-term weight loss after bariatric surgery., Methods: MEDLINE, PubMed, and Embase were searched, and data were analyzed using ReviewManager (RevMan) version 5.4. The datasets were divided into two subgroups based on postoperative time, and the outcome measure was the percentage of total weight loss. Meta-regression analysis was performed, and the outcome was presented as the weighed mean difference of percentage of total weight loss., Results: The results showed that patients with mutations in the leptin-melanocortin pathway experienced 3.03% lower total weight loss after bariatric surgery (mean difference, -3.03; 95% CI: -3.63 to -2.44), mainly reflected in lower long-term postoperative weight loss (mean difference, -3.43; 95% CI: -4.09 to -2.77), whereas mutation carriers exhibited a magnitude of short-term postoperative weight loss that was similar to patients without such mutations (total difference value, -1.13; 95% CI: -2.57 to 0.31)., Conclusions: Mutations in leptin-melanocortin pathway genes reduce long-term weight loss after bariatric surgery, whereas this effect may not be reflected during the period of rapid weight loss within 12 months. These genetic variants increase the difficulties in maintaining patients' long-term weight loss., (© 2024 The Obesity Society.)
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- 2024
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11. Efficacy of a Comprehensive Weight Reduction Intervention in Male Adolescents With Different FTO Genotypes.
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Roumi Z, Salimi Z, Mahmoudi Z, Mobarakeh KA, Ladaninezhad M, Zeinalabedini M, Keshavarz Mohammadian M, Shamsi-Goushki A, Saeedirad Z, Bahar B, Khoshdooz S, Kalantari N, Azizi Tabesh G, Doaei S, and Gholamalizadeh M
- Subjects
- Humans, Adolescent, Male, Body Mass Index, Genotype, Obesity genetics, Obesity therapy, Weight Loss genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Overweight genetics, Polymorphism, Single Nucleotide
- Abstract
Background: The FTO gene polymorphisms may influence the effects of lifestyle interventions on obesity. The present study aimed to assess the influence of the rs9930506 FTO gene polymorphism on the success of a comprehensive weight loss intervention in male adolescents with overweight and obesity., Methods: This study was carried out on 96 adolescent boys with overweight and obesity who were randomly assigned to the intervention (n = 53) and control (n = 43) groups. The blood samples of the participants were collected, and the FTO gene was genotyped for the rs9930506 polymorphism. A comprehensive lifestyle intervention including changes in diet and physical activity was performed for 8 weeks in the intervention group., Results: Following the lifestyle intervention, BMI and fat mass decreased significantly in the intervention group compared with the control group (both p < 0.05), while no change was found in weight, height or body muscle percentage between the groups. The participants in the intervention group with the AA/AG genotype and not in carriers of the GG genotype had a significantly higher reduction in BMI (-1.21 vs. 1.87 kg/m
2 , F = 4.07, p < 0.05) compared with the control group., Conclusion: The intervention in individuals with the AA/AG genotype has been significantly effective in weight loss compared with the control group. The intervention had no association effect on anthropometric indices in adolescents with the GG genotype of the FTO rs9930506 polymorphism., Trial Registration: Name of the registry: National Nutrition and Food Technology Research Institute; Trial registration number: IRCT2016020925699N2; Date of registration: 24/04/2016; URL of trial registry record: https://www.irct.ir/trial/21447., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)- Published
- 2024
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12. Impact of polygenic score for BMI on weight loss effectiveness and genome-wide association analysis.
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Dashti HS, Scheer FAJL, Saxena R, and Garaulet M
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- Adult, Female, Humans, Male, Middle Aged, Multifactorial Inheritance genetics, Polymorphism, Single Nucleotide, Body Mass Index, Genome-Wide Association Study, Obesity genetics, Weight Loss genetics
- Abstract
Background: While environmental factors play an important role in weight loss effectiveness, genetics may also influence its success. We examined whether a genome-wide polygenic score for BMI was associated with weight loss effectiveness and aimed to identify common genetic variants associated with weight loss., Methods: Participants in the ONTIME study (n = 1210) followed a uniform, multimodal behavioral weight-loss intervention. We first tested associations between a genome-wide polygenic score for higher BMI and weight loss effectiveness (total weight loss, rate of weight loss, and attrition). We then conducted a genome-wide association study (GWAS) for weight loss in the ONTIME study and performed the largest weight loss meta-analysis with earlier studies (n = 3056). Lastly, we ran exploratory GWAS in the ONTIME study for other weight loss outcomes and related factors., Results: We found that each standard deviation increment in the polygenic score was associated with a decrease in the rate of weight loss (Beta (95% CI) = -0.04 kg per week (-0.06, -0.01); P = 3.7 × 10
-03 ) and with higher attrition after adjusting by treatment duration. No associations reached genome-wide significance in meta-analysis with previous GWAS studies for weight loss. However, associations in the ONTIME study showed effects consistent with published studies for rs545936 (MIR486/NKX6.3/ANK1), a previously noted weight loss locus. In the meta-analysis, each copy of the minor A allele was associated with 0.12 (0.03) kg/m2 higher BMI at week five of treatment (P = 3.9 × 10-06 ). In the ONTIME study, we also identified two genome-wide significant (P < 5×10-08 ) loci for the rate of weight loss near genes implicated in lipolysis, body weight, and metabolic regulation: rs146905606 near NFIP1/SPRY4/FGF1; and rs151313458 near LSAMP., Conclusion: Our findings are expected to help in developing personalized weight loss approaches based on genetics., Clinical Trial Registration: Obesity, Nutrigenetics, Timing, and Mediterranean (ONTIME; clinicaltrials.gov: NCT02829619) study., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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13. Association of rs3138167 polymorphism with metabolic response after a hypocaloric Mediterranean diet.
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de Luis Román D, Primo Martín D, and Izaola Jáuregui O
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- Humans, Male, Female, Middle Aged, Adult, Weight Loss genetics, Resistin genetics, Resistin blood, Diet, Reducing, Insulin Resistance genetics, Caloric Restriction methods, Insulin blood, Diet, Mediterranean, Polymorphism, Single Nucleotide, Obesity genetics, Obesity diet therapy
- Abstract
Introduction: Background: the single nucleotide polymorphism (SNP) (rs3138167) is a polymorphism that has been associated with metabolic disorder in obese subjects and its effect on the metabolic response after a dietary intervention has not been evaluated. Objective: our aim was to analyze the effects of the rs3138167 on metabolic changes secondary to weight loss with a hypocaloric diet with a Mediterranean pattern. Method: one thousand and eight Caucasian obese patients were evaluated. Before and after 12 weeks on a hypocaloric diet with Mediterranean pattern, an anthropometric evaluation and a biochemical analysis were performed. The statistical analysis was performed as a dominant model (CC vs CT + TT). Results: the values of insulin, HOMA-IR and resistin were higher in T allele carriers than non-T allele carriers in pre- and post-intervention time. In non-T allele carriers, resistin, insulin, HOMA-IR, triglycerides and C-reactive protein levels decreased. The improvement was statistically superior in non-T allele carriers; resistin (-1.2 ± 0.2 ng/dl; p = 0.02), triglycerides (-18.3 ± 4.3 mg/dl; p = 0.02), C-reactive protein (-2.6 ± 0.3 mg/dl; p = 0.02), insulin -4.4 ± 1.9 mUI/l; p = 0.02) and HOMA-IR (-2.1 ± 0.7; p = 0.03). Conclusion: we report an association of rs3138167 with a worse metabolic response (insulin, HOMA-IR, triglyceride and C-reactive protein) in T allele carriers after weight loss with a hypocaloric diet with Mediterranean pattern.
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- 2024
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14. Analysis of 16s rRNA Gene Sequencing in Feces: The Impact of Bariatric Surgery on the Gut Microbiota in Patients with Obesity.
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Zhang L, Cheng X, Xia L, Liu N, Liu L, Liu S, Wang S, and Yin J
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- Humans, RNA, Ribosomal, 16S genetics, Genes, rRNA, Phylogeny, Obesity surgery, Feces microbiology, Weight Loss genetics, Gastrointestinal Microbiome, Obesity, Morbid surgery, Bariatric Surgery methods
- Abstract
Purpose: Obesity is a risk factor for many chronic diseases. This study aimed to investigate the effect of bariatric surgery on the gut microbiota from patients with obesity., Materials and Methods: The microbiota composition from stool samples before and after bariatric surgery were identified using bacterial 16S rRNA gene sequencing. Based on the speed of weight loss, patients were classified as the slow-loss group and fast-loss group. The ɑ- and β-diversity analysis was done to compare the species richness, evenness, and overall structure of the microbiota between different groups. Next, linear discriminant analysis effect size (LEfSe) and receiver operating characteristic (ROC) analysis were implemented to identify high-dimensional biomarkers and significantly different species of microbial taxa between different groups. Finally, the pathway analysis was inferred using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict the functional profiling of microbial communities., Results: β-diversity analysis suggested that species diversity of preoperative samples of slow-loss group was significantly higher than the fast-loss group. High levels of Oscillospira and Abiotrophia in the preoperative gut microbiota may lead to poor postoperative weight loss. For patients with poor postoperative weight loss due to changes in gut microbiota, the gut microbiota is mainly composed of Lactobacillus. For patients with good postoperative results, the gut microbiota is mainly composed of Escherichia, Robinsonella, and Dialister. In addition, multiple metabolic-related pathways were significantly different between the four groups., Conclusion: This comparative study revealed biomarker species based on microfloral composition in patients with obesity before and after bariatric surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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15. Interaction Effects of FTO and MC4R Polymorphisms on Total Body Weight Loss, Post-Surgery Weight, and Post-Body Mass Index after Bariatric Surgery.
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Perez-Luque E, Daza-Hernandez ES, Figueroa-Vega N, Cardona-Alvarado MI, Muñoz-Montes N, and Martinez-Cordero C
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- Humans, Male, Female, Adult, Middle Aged, Obesity, Morbid surgery, Obesity, Morbid genetics, Retrospective Studies, Haplotypes, Genotype, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Receptor, Melanocortin, Type 4 genetics, Weight Loss genetics, Body Mass Index, Bariatric Surgery, Polymorphism, Single Nucleotide
- Abstract
Bariatric surgery (BS) is considered the most effective intervention for patients with severe obesity and is used to maintain long-term weight loss and glycemic control. The aim of this study was to analyze the effects of genotypes and haplotypes of the fat mass and obesity-associated ( FTO ) and melanocortin 4 receptor ( MC4R) genes on total body weight loss (TBWL), post-surgery weight, and post-BMI after bariatric surgery. We retrospectively selected 101 patients from Bajio High Specialty Regional Hospital, León Guanajuato, México, who underwent Roux-en-Y gastric bypass (RYGB) to determine their body mass index (BMI), blood pressure, biochemical characteristics, and comorbidities. Post-surgery, patients were referred for registered anthropometry and blood pressure. Glucose, lipid and hepatic profiles, and insulin, leptin, and ghrelin levels were measured, and rs9939609, rs9930506, and rs1421085 FTO and rs17782313 MC4R polymorphisms were genotyped. Six (4-8) years after BS, post-surgery weight was greater in carriers of the rs9939609 and rs1421085 risk genotypes. TBWL was lower for the rs9930506 and rs1421085 risk genotypes. Insulin and HOMA-IR were greater in patients with the three FTO polymorphisms. There were significant interaction effects of the rs9930506 and rs1421085 FTO risk genotypes on weight and BMI in response to BS. No association was found with the MC4R polymorphism. The genotypes and haplotypes of the FTO gene influence post-surgery weight, TBWL, insulin levels, and HOMA-IR.
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- 2024
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16. Genetics of Exercise and Diet-Induced Fat Loss Efficiency: A Systematic Review.
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Bojarczuk A, Egorova ES, Dzitkowska-Zabielska M, and Ahmetov II
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- Humans, Genetic Markers, Weight Loss genetics, Diet, Obesity genetics, Obesity prevention & control, Exercise
- Abstract
Physical exercise and dieting are well-known and effective methods for fat loss and improving cardiovascular health. However, different individuals often react differently to the same exercise regimen or dietary plan. While specific individuals may undergo substantial fat loss, others may observe only limited effects. A wide range of inter-individual variability in weight gain and changes in body composition induced by physical exercises and diets led to an investigation into the genetic factors that may contribute to the individual variations in such responses. This systematic review aimed at identifying the genetic markers associated with fat loss resulting from diet or exercise. A search of the current literature was performed using the PubMed database. Forty-seven articles met the inclusion criteria when assessing genetic markers associated with weight loss efficiency in response to different types of exercises and diets. Overall, we identified 30 genetic markers of fat-loss efficiency in response to different kinds of diets and 24 in response to exercise. Most studies (n = 46) used the candidate gene approach. We should aspire to the customized selection of exercise and dietary plans for each individual to prevent and treat obesity., (© Journal of Sports Science and Medicine.)
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- 2024
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17. Association between variants in TCF7L2 , CTRB1/2 , and GLP-1R genes and response to therapy with glucagon-like peptide-1 receptor agonists.
- Author
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Kyriakidou A, Kyriazou AV, Koufakis T, Vasilopoulos Y, Avramidis I, Baltagiannis S, Goulis DG, and Kotsa K
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Blood Glucose drug effects, Genotype, Greece, Polymorphism, Single Nucleotide, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 genetics, Glucagon-Like Peptide-1 Receptor Agonists therapeutic use, Hypoglycemic Agents therapeutic use, Transcription Factor 7-Like 2 Protein genetics, Weight Loss genetics, Weight Loss drug effects
- Abstract
Objectives: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2 , CTRB1/2 , and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM)., Methods: Patients ( n = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria., Results: Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex ( p = 0.03) and lower baseline weight ( p = 0.024) were associated with an improved glycemic and weight loss response, respectively., Conclusion: There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.
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- 2024
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18. The Impact of Glucomannan, Inulin, and Psyllium Supplementation (Soloways TM ) on Weight Loss in Adults with FTO, LEP, LEPR, and MC4R Polymorphisms: A Randomized, Double-Blind, Placebo-Controlled Trial.
- Author
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Pokushalov E, Ponomarenko A, Garcia C, Pak I, Shrainer E, Seryakova M, Johnson M, and Miller R
- Subjects
- Adult, Humans, Polymorphism, Single Nucleotide, Obesity drug therapy, Obesity genetics, Obesity epidemiology, Body Weight genetics, Weight Loss genetics, Dietary Supplements, Body Mass Index, Receptor, Melanocortin, Type 4 genetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Inulin, Psyllium therapeutic use, Mannans
- Abstract
This study aimed to determine the impact of a fiber supplement on body weight and composition in individuals with obesity with specific genetic polymorphisms. It involved 112 adults with obesity, each with at least one minor allele in the FTO, LEP, LEPR, or MC4R polymorphism. Participants were randomized to receive either a fiber supplement (glucomannan, inulin, and psyllium) or a placebo for 180 days. The experimental group showed significant reductions in body weight (treatment difference: -4.9%; 95% CI: -6.9% to -2.9%; p < 0.01) and BMI (treatment difference: -1.4 kg/m
2 ; 95% CI: -1.7 to -1.2; p < 0.01) compared to placebo. Further significant decreases in fat mass (treatment difference: -13.0%; 95% CI: -14.4 to -11.7; p < 0.01) and visceral fat rating (treatment difference: -1.3; 95% CI: -1.6 to -1.0; p < 0.01) were noted. Homozygous minor allele carriers experienced greater decreases in body weight (treatment difference: -3.2%; 95% CI: -4.9% to -1.6%; p < 0.01) and BMI (treatment difference: -1.2 kg/m2 ; 95% CI: -2.0 to -0.4; p < 0.01) compared to heterozygous allele carriers. These carriers also had a more significant reduction in fat mass (treatment difference: -9.8%; 95% CI: -10.6 to -9.1; p < 0.01) and visceral fat rating (treatment difference: -0.9; 95% CI: -1.3 to -0.5; p < 0.01). A high incidence of gastrointestinal events was reported in the experimental group (74.6%), unlike the placebo group, which reported no side effects. Dietary supplementation with glucomannan, inulin, and psyllium effectively promotes weight loss and improves body composition in individuals with obesity, particularly those with specific genetic polymorphisms.- Published
- 2024
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19. Novel markers and networks related to restored skeletal muscle transcriptome after bariatric surgery.
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Ouni M, Kovac L, Gancheva S, Jähnert M, Zuljan E, Gottmann P, Kahl S, de Angelis MH, Roden M, and Schürmann A
- Subjects
- Humans, Animals, Mice, Obesity genetics, Obesity surgery, Obesity metabolism, Muscle, Skeletal metabolism, Weight Loss genetics, Fatty Acids, Nonesterified metabolism, Gene Regulatory Networks, Transcriptome, Bariatric Surgery
- Abstract
Objective: The aim of this study was to discover novel markers underlying the improvement of skeletal muscle metabolism after bariatric surgery., Methods: Skeletal muscle transcriptome data of lean people and people with obesity, before and 1 year after bariatric surgery, were subjected to weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Results of LASSO were confirmed in a replication cohort., Results: The expression levels of 440 genes differing between individuals with and without obesity were no longer different 1 year after surgery, indicating restoration. WGCNA clustered 116 genes with normalized expression in one major module, particularly correlating to weight loss and decreased plasma free fatty acids (FFA), 44 of which showed an obesity-related phenotype upon deletion in mice. Among the genes of the major module, 105 represented prominent markers for reduced FFA concentration, including 55 marker genes for decreased BMI in both the discovery and replication cohorts., Conclusions: Previously unknown gene networks and marker genes underlined the important role of FFA in restoring muscle gene expression after bariatric surgery and further suggest novel therapeutic targets for obesity., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)
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- 2024
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20. Impact of the rs822393 Variant on Adiponectin Levels and Metabolic Parameters after Weight Loss Secondary to a High-Fat Hypocaloric Diet with Mediterranean Pattern.
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Primo D, Izaola O, Lopez Gomez JJ, Rico D, and de Luis DA
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- Humans, Male, Female, Middle Aged, Adult, Polymorphism, Single Nucleotide, Insulin Resistance, Genotype, Diet, Reducing, Leptin blood, Leptin genetics, Caloric Restriction, Gene Frequency, Alleles, Body Mass Index, Adiponectin blood, Adiponectin genetics, Weight Loss genetics, Diet, Mediterranean, Obesity genetics, Obesity diet therapy, Diet, High-Fat
- Abstract
Introduction: The effects of the rs822393 variant of ADIPOQ gene on metabolic parameters such as insulin resistance and adiponectin levels following weight loss through dietary intervention are still uncertain. The aim of this study was to evaluate the role of rs822393 of ADIPOQ gene on adiponectin levels and metabolic parameters after weight loss with a high-fat hypocaloric diet with Mediterranean pattern during 12 weeks., Methods: A population of 283 patients with obesity was allocated to a dietary intervention trial with a high-fat hypocaloric diet during 12 weeks. Adiposity and biochemical parameters were determined. rs822393 was assessed with a dominant model analysis (CC vs. CT + TT)., Results: These patients had three different genotypes: CC (59.0%), CT (33.6%), and TT (7.4%). The allelic frequencies for C and T were 0.89 and 0.20, respectively. Basal and post-intervention HDL cholesterol, adiponectin levels, and adiponectin/leptin ratio were lower in T-allele than non-T-allele carriers. After dietary intervention, BMI, weight, fat mass, waist circumference, systolic blood pressure, insulin, HOMA-IR, leptin, total cholesterol, and LDL cholesterol levels improved significantly in both genotype groups. Moreover, HDL cholesterol (CC vs. CT + TT) (delta: 8.9 ± 1.1 mg/dL vs. 1.7 ± 0.8 mg/dL; p = 0.02), serum adiponectin in non-T-allele carriers (43.1 ± 5.9 ng/dL vs. 2.8 ± 3 0.0 ng/dL; p = 0.01), and adiponectin/leptin ratio (1.37 ± 0.1 units vs. 0.17 ± 0.08 units; p = 0.02) improved only in non-T-allele carriers after weight loss., Conclusion: Individuals with obesity and without the T allele of rs822393 experienced improvements in adiponectin levels, adiponectin/leptin ratio, and HDL cholesterol levels after following a high-fat hypocaloric diet with a Mediterranean pattern., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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21. Transcriptional and epigenetic changes after dietary and surgical weight loss interventions in an animal model of obesity.
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Cremades M, Talavera-Urquijo E, Beisani M, Pappa S, Jordà M, Tarascó J, Moreno P, Caballero A, Martínez-López E, Pellitero S, and Balibrea JM
- Subjects
- Rats, Male, Animals, Rats, Wistar, Disease Models, Animal, Gastrectomy methods, Diet, High-Fat, Epigenesis, Genetic, RNA, Messenger, Obesity genetics, Obesity surgery, Weight Loss genetics
- Abstract
Background: Identifying determinants that can predict response to weight loss interventions is imperative for optimizing therapeutic benefit. We aimed to identify changes in DNA methylation and mRNA expression of a subset of target genes following dietary and surgical interventions in high-fat-diet (HFD)-induced obese rats., Methods: Forty-two adult Wistar Han male rats were divided into two groups: control rats (n = 7) and obese rats (n = 28), fed a HFD for 10 weeks (t10). Obese rats were randomly subdivided into five intervention groups (seven animals per group): (i) HFD; (ii) very-low-calorie diet (VLCD); (iii) sham surgery, and (iv) sleeve gastrectomy (SG). At week sixteen (t16), animals were sacrificed and tissue samples were collected to analyze changes in DNA methylation and mRNA expression of the selected genes., Results: By type of intervention, the surgical procedures led to the greatest weight loss. Changes in methylation and/or expression of candidate genes occurred proportionally to the effectiveness of the weight loss interventions. Leptin expression, increased sixfold in the visceral fat of the obese rats, was partially normalized after all interventions. The expression of fatty acid synthase (FASN) and monocyte chemoattractant protein 1 (MCP-1) genes, which was reduced 0.5- and 0.15-fold, respectively, in the liver tissue of obese rats, were completely normalized after weight loss interventions, particularly after surgical interventions. The upregulation of FASN and MCP-1 gene expression was accompanied by a significant reduction in promoter methylation, up to 0.5-fold decrease in the case of the FASN (all intervention groups) and a 0.8-fold decrease in the case of the MCP-1 (SG group)., Conclusions: Changes in tissue expression of specific genes involved in the pathophysiological mechanisms of obesity can be significantly attenuated following weight loss interventions, particularly surgery. Some of these genes are regulated by epigenetic mechanisms., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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22. Subcutaneous adipose tissue expression of genes associated with glucocorticoid action: relationship with insulin sensitivity, obesity, and weight loss.
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Strączkowski M, Stefanowicz M, Nikołajuk A, and Karczewska-Kupczewska M
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- Humans, Obesity complications, Subcutaneous Fat metabolism, Weight Loss genetics, Glucocorticoids therapeutic use, Insulin Resistance genetics
- Published
- 2023
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23. CETP and APOA2 polymorphisms are associated with weight loss and healthy eating behavior changes in response to digital lifestyle modifications.
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Kim M, Lee S, Cho E, Hong KW, You SJ, and Choi HJ
- Subjects
- Humans, Apolipoprotein A-II, Body Mass Index, Cholesterol Ester Transfer Proteins genetics, Feeding Behavior, Genotype, Life Style, Obesity genetics, Polymorphism, Single Nucleotide, Diet, Healthy, Weight Loss genetics
- Abstract
Response to digital healthcare lifestyle modifications is highly divergent. This study aimed to examine the association between single nucleotide polymorphism (SNP) genotypes and clinical efficacy of a digital healthcare lifestyle modification. We genotyped 97 obesity-related SNPs from 45 participants aged 18-39 years, who underwent lifestyle modification via digital cognitive behavioral therapy for obesity for 8 weeks. Anthropometric, eating behavior phenotypes, and psychological measures were analyzed before and after the intervention to identify their clinical efficacy. CETP (rs9939224) SNP significantly predict "super-responders" with greater body mass index (BMI) reduction (p = 0.028; GG - 2.91%, GT - 9.94%), while APOA2 (rs5082) appeared to have some potential for predicting "poor-responders" with lower BMI reduction (p = 0.005; AA - 6.17%, AG + 2.05%, and GG + 5.11%). These SNPs was also associated with significant differences in eating behavior changes, healthy diet proportions, health diet diversity, emotional and restrained eating behavior changes. Furthermore, classification using gene-gene interactions between rs9939224 and rs5082 significantly predicted the best response, with a greater decrease in BMI (p = 0.038; - 11.45% for the best response group (CEPT GT/TT × APOA2 AA) vs. + 2.62% for the worst response group (CEPT GG × APOA2 AG/GG)). CETP and APOA2 SNPs can be used as candidate markers to predict the efficacy of digital healthcare lifestyle modifications based on genotype-based precision medicine.Trial registration: NCT03465306, ClinicalTrials.gov. Registered March, 2018., (© 2023. The Author(s).)
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- 2023
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24. A Predictive Tool Based on DNA Methylation Data for Personalized Weight Loss through Different Dietary Strategies: A Pilot Study.
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García-Álvarez NC, Riezu-Boj JI, Martínez JA, García-Calzón S, and Milagro FI
- Subjects
- Humans, Pilot Projects, Weight Loss genetics, Diet, Fat-Restricted, Diet, Reducing, DNA Methylation, Obesity
- Abstract
Background and Aims: Obesity is a public health problem. The usual treatment is a reduction in calorie intake and an increase in energy expenditure, but not all individuals respond equally to these treatments. Epigenetics could be a factor that contributes to this heterogeneity. The aim of this research was to determine the association between DNA methylation at baseline and the percentage of BMI loss (%BMIL) after two dietary interventions, in order to design a prediction model to evaluate %BMIL based on methylation data., Methods and Results: Spanish participants with overweight or obesity ( n = 306) were randomly assigned to two lifestyle interventions with hypocaloric diets: one moderately high in protein (MHP) and the other low in fat (LF) for 4 months (Obekit study; ClinicalTrials.gov ID: NCT02737267). Basal DNA methylation was analyzed in white blood cells using the Infinium MethylationEPIC array. After identifying those methylation sites associated with %BMIL ( p < 0.05 and SD > 0.1), two weighted methylation sub-scores were constructed for each diet: 15 CpGs were used for the MHP diet and 11 CpGs for the LF diet. Afterwards, a total methylation score was made by subtracting the previous sub-scores. These data were used to design a prediction model for %BMIL through a linear mixed effect model with the interaction between diet and total score., Conclusion: Overall, DNA methylation predicts the %BMIL of two 4-month hypocaloric diets and was able to determine which type of diet is the most appropriate for each individual. The results of this pioneer study confirm that epigenetic biomarkers may be further used for precision nutrition and the design of personalized dietary strategies against obesity.
- Published
- 2023
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25. Under pressure-exploring partner changes, physiological responses and telomere dynamics in northern gannets across varying breeding conditions.
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Pelletier D, Blier PU, Vézina F, Dufresne F, Paquin F, Christen F, and Guillemette M
- Subjects
- Humans, Animals, Telomere genetics, Weight Loss genetics, Breeding, Inflammation genetics, Oxygen, Antioxidants, Birds genetics
- Abstract
Background: Life history theory predicts trade-offs between reproduction and survival in species like the northern gannet ( Morus bassanus ). During breeding, demanding foraging conditions lead them to expand their foraging range and diversify their diet, increasing the risk of reproductive failure. Changing partners may enhance breeding success but lead to more physiological costs., Methods: To investigate the physiological costs of reproduction upon partner changes, we measured and compared 21 biomarkers related to telomere dynamics, oxidative stress, inflammation, hematology, nutritional status, and muscle damage. We used a longitudinal approach with gannets ( n = 38) over three contrasting years (2017, 2018 and 2019)., Results: Our results suggest that annual breeding conditions exert a greater influence on physiological changes than partnership status. Individuals that changed partner experienced greater short-term stress than retained partners. This transient increase in stress was marked by short-term increases in oxidative lipid damage, lower antioxidant capacity, signs of inflammation, and greater weight loss than individuals that retained partners. During favorable conditions, individuals that changed mates had stabilized telomere length, decreased antioxidant capacity, glucose concentration, and muscle damage, along with increased oxygen transport capacity. Conversely, unfavorable breeding conditions led to increased telomere attrition, stabilized antioxidant capacity, decreased inflammation susceptibility, diminished oxygen transport capacity, and increased muscle damage. In the cases where partners were retained, distinct physiological changes were observed depending on the year's conditions, yet the telomere dynamics remained consistent across both partnership status categories. During the favorable year, there was an increase in unsaturated fatty acids and oxygen transport capacity in the blood, coupled with a reduction in inflammation potential and protein catabolism. In contrast, during the unfavorable year in the retained mates, we observed an increase in oxidative DNA damage, antioxidant capacity, weight loss, but a decrease in inflammation susceptibility as observed in changed mates., Discussion: Our study shows that behavioral flexibility such as mate switching can help seabirds cope with the challenges of food scarcity during reproduction, but these coping strategies may have a negative impact on physiological status at the individual level. In addition, the marked reduction in telomere length observed during harsh conditions, coupled with the stabilization of telomere length in favorable conditions, highlights the long-term physiological impact of annual breeding conditions on seabirds. These findings underscore the effect on their potential survival and fitness, emphasizing that the influence of annual breeding conditions is greater than that of partnership status., Competing Interests: The authors declare there are no competing interests., (©2023 Pelletier et al.)
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- 2023
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26. Genetic variants associated with weight loss and metabolic outcomes after bariatric surgery: A systematic review.
- Author
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van der Meer R, Mohamed SA, Monpellier VM, Liem RSL, Hazebroek EJ, Franks PW, Frayling TM, Janssen IMC, and Serlie MJ
- Subjects
- Humans, Weight Loss genetics, Polymorphism, Single Nucleotide, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Bariatric Surgery
- Abstract
The extent to which genetic variations contribute to interindividual differences in weight loss and metabolic outcomes after bariatric surgery is unknown. Identifying genetic variants that impact surgery outcomes may contribute to clinical decision making. This review evaluates current evidence addressing the association of genetic variants with weight loss and changes in metabolic parameters after bariatric surgery. A search was conducted using Medline, Embase, Scopus, Web of Science, and Cochrane Library. Fifty-two eligible studies were identified. Single nucleotide polymorphisms (SNPs) at ADIPOQ (rs226729, rs1501299, rs3774261, and rs17300539) showed a positive association with postoperative change in measures of glucose homeostasis and lipid profiles (n = 4), but not with weight loss after surgery (n = 6). SNPs at FTO (rs11075986, rs16952482, rs8050136, rs9939609, rs9930506, and rs16945088) (n = 10) and MC4R (rs11152213, rs476828, rs2229616, rs9947255, rs17773430, rs5282087, and rs17782313) (n = 9) were inconsistently associated with weight loss and metabolic improvement. Four studies examining the UCP2 SNP rs660339 reported associations with postsurgical weight loss. In summary, there is limited evidence supporting a role for specific genetic variants in surgical outcomes after bariatric surgery. Most studies have adopted a candidate gene approach, limiting the scope for discovery, suggesting that the absence of compelling evidence is not evidence of absence., (© 2023 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)
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- 2023
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27. Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood.
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ElGendy K, Malcomson FC, Afshar S, Bradburn MD, and Mathers JC
- Subjects
- Humans, Rectum, Pro-Opiomelanocortin genetics, Obesity genetics, Obesity surgery, Obesity complications, DNA Methylation genetics, Biomarkers, Inflammation complications, DNA, Mucous Membrane, Weight Loss genetics, Cell-Free Nucleic Acids, Bariatric Surgery methods, Colorectal Neoplasms genetics
- Abstract
Background: DNA methylation is an epigenetic mechanism through which environmental factors including nutrition and inflammation influence health. Obesity is a major modifiable risk factor for many common diseases including cardiovascular diseases and cancer. In particular, obesity-induced inflammation resulting from aberrantly-methylated inflammatory genes may drive risk of several non-communicable diseases including colorectal cancer (CRC). This study is the first to investigate the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in the rectum and in cell-free DNA (cfDNA) from blood., Subjects and Methods: DNA methylation was quantified in rectal mucosal biopsies and cfDNA from serum of 28 participants with obesity before and 6 months after BS, as well as in 12 participants without obesity (control group) matched for age and sex from the Biomarkers Of Colorectal cancer After Bariatric Surgery (BOCABS) Study. DNA methylation of LEP, IL6, POMC, LINE1, MAPK7 and COX2 was quantified by pyrosequencing., Results: BMI decreased significantly from 41.8 kg/m
2 pre-surgery to 32.3 kg/m2 at 6 months after BS. Compared with the control group, obesity was associated with lower LEP methylation in both the rectal mucosa and in cfDNA from serum. BS normalised LEP methylation in DNA from the rectal mucosa but not in cfDNA. BS decreased methylation of some CpG sites of LINE1 in the rectal mucosal DNA and in cfDNA to levels comparable with those in participants without obesity. Methylation of POMC in rectal mucosal DNA was normalised at 6 months after BS., Conclusion: BS reversed LINE1, POMC and LEP methylation in the rectal mucosa of patients with obesity to levels similar to those in individuals without obesity. These findings support current evidence of effects of BS-induced weight loss on reversibility of DNA methylation in other tissues. The DNA methylation changes in the rectal mucosa shows promise as a biomarker for objective assessment of effects of weight loss interventions on risk of cancer and other diseases., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2023
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28. Role of beta-2 adrenergic receptor polymorphism (rs1042714) on body weight and glucose metabolism response to a meal-replacement hypocaloric diet.
- Author
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de Luis DA, Izaola O, Primo D, and Gómez JJL
- Subjects
- Female, Humans, Body Weight, Cholesterol, LDL, Diet, Reducing methods, Genotype, Glucose, Obesity metabolism, Polymorphism, Single Nucleotide, Receptors, Adrenergic, beta-2 genetics, Weight Loss genetics, Insulin Resistance genetics, Insulins genetics
- Abstract
Objectives: The beta-2 adrenergic receptor (ADRB2) is involved in energy balance regulation. The objective of our study was to evaluate the role of the rs1042714 genetic variant of ADRB2 gene on weight loss, body composition, and metabolic changes secondary to partial meal replacement (pMR) hypocaloric diet in women with obesity., Methods: We conducted an interventional study in 95 premenopausal women with body mass index ≥ 35 kg/m
2 . The subjects received two intakes per day of a normocaloric hyperproteic formula during 12 wk of a pMR diet. Body weight, body mass index, fat mass, waist circumference, lipid profile, fasting insulin levels, and homeostasis model assessment for insulin resistance were determined. All patients were genotyped rs1042714 and evaluated in a dominant model (CC versus CG + GG)., Results: Genotype frequencies were 31 (37.3%), 38 (45.8%), and 14 (16.9%) for the CC, CG, and GG genotypes, respectively. We found significant interaction effects between ADRB2 variant and pMR-induced changes (CC versus CG + GG) on body weight (-7.1 ± 0.3 versus -13.5 ± 0.5 kg; P = 0.03), body mass index (-0.9 ± 0.1 versus -1.2 ± 0.2 kg/m2 ; P = 0.03), fat mass (-4.9 ± 0.5 versus -10.2 ±1.2 kg; P = 0.01), waist circumference (-5.1 ± 0.2 versus -10.1 ± 1.9 cm; P = 0.03), glucose (-5.1 ± 1.3 versus -12.5 ± 2.5 mg/dL; P = 0.03), total cholesterol (-18.1 ± 9.3 versus -33.5 ± 4.5 mg/dL; P = 0.03), low-density lipoprotein cholesterol (-9.1 ± 5.3 versus -24.5 ± 4.1 mg/dL; P = 0.04), triacylglycerol levels (-6.1 ± 5.3 versus -31.5 ± 9.5 mg/dL; P = 0.04), fasting insulin levels (-1.8 ± 0.3 versus -6.3 ± 0.5 IU/L; P = 0.03), and homeostasis model assessment for insulin resistance (-0.6 ± 0.3 versus -1.9 ± 0.5 U; P = 0.03). The odds ratio to improve alteration in glucose metabolism adjusted by age and weight loss throughout the study was 0.26 (95% CI, 0.07-0.95; P = 0.02) in G allele carriers., Conclusions: The G allele of rs1042714 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement of insulin resistance and percentage of impaired glucose metabolism in G allele carriers., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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29. rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population.
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Clark JSC, Podsiadło K, Sobalska-Kwapis M, Marciniak B, Rydzewska K, Ciechanowicz A, van de Wetering T, and Strapagiel D
- Subjects
- Humans, Male, Female, Body Mass Index, Poland, Genotype, Weight Loss genetics, Codon, Polymorphism, Single Nucleotide, Obesity complications, Adiposity genetics
- Abstract
There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m
2 : [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10-5 ; beta: - 0.0458, 95% confidence interval (CI) - 0.0732 : - 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10-4 ; beta: - 0.0573, CI - 0.0947 : - 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression., (© 2023. Springer Nature Limited.)- Published
- 2023
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30. The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a Randomized Clinical Trial.
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Höchsmann C, Yang S, Ordovás JM, Dorling JL, Champagne CM, Apolzan JW, Greenway FL, Cardel MI, Foster GD, and Martin CK
- Subjects
- Humans, Female, Male, Overweight genetics, Overweight therapy, Dietary Carbohydrates, Weight Loss genetics, Diet, Fat-Restricted, Diet, Reducing, Obesity genetics, Obesity therapy
- Abstract
Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m
2 , 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (-5.3 kg [SD:1.0]) and genotype-discordant diets (-4.8 kg [SD:1.1]; adjusted difference: -0.6 kg [95% CI: -2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466., (© 2023. Springer Nature Limited.)- Published
- 2023
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31. Abdominal Obesity Genetic Variants Predict Waist Circumference Regain After Weight Loss.
- Author
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Christiansen MR, Kilpeläinen TO, and McCaffery JM
- Subjects
- Male, Humans, Female, Waist Circumference genetics, Obesity, Abdominal genetics, Obesity genetics, Obesity complications, Weight Loss genetics, Body Mass Index, Waist-Hip Ratio, Risk Factors, Weight Gain genetics, Genetic Predisposition to Disease
- Abstract
Although many individuals are able to achieve weight loss, maintaining this loss over time is challenging. We aimed to study whether genetic predisposition to general or abdominal obesity predicts weight regain after weight loss. We examined the associations between genetic risk scores for higher BMI and higher waist-to-hip ratio adjusted for BMI (WHRadjBMI) with changes in weight and waist circumference up to 3 years after a 1-year weight loss program in participants (n = 822 women, n = 593 men) from the Look AHEAD (Action for Health in Diabetes) study who had lost ≥3% of their initial weight. Genetic predisposition to higher BMI or WHRadjBMI was not associated with weight regain after weight loss. However, the WHRadjBMI genetic score did predict an increase in waist circumference independent of weight change. To conclude, a genetic predisposition to higher WHRadjBMI predicts an increase in abdominal obesity after weight loss, whereas genetic predisposition to higher BMI is not predictive of weight regain. These results suggest that genetic effects on abdominal obesity may be more pronounced than those on general obesity during weight regain., Article Highlights: Nearly all individuals who intentionally lose weight experience weight regain. Individuals with a higher genetic risk for abdominal adiposity experience increased regain in waist circumference after weight loss. Genetic predisposition to higher BMI does not predict weight regain after weight loss., (© 2023 by the American Diabetes Association.)
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- 2023
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32. RS2289487 variation in PERILIPIN gene is a predictor of weight loss and protection against impaired glucose metabolism after a meal-replacement diet in postmenopausal obese females.
- Author
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de Luis D, Izaola O, Primo D, and Aller R
- Subjects
- Female, Humans, Diet, Reducing methods, Glucose, Perilipin-1 genetics, Polymorphism, Single Nucleotide, Postmenopause, Weight Loss genetics, Insulin Resistance genetics, Obesity metabolism
- Abstract
Objective: The PERILIPIN1 (PLIN1) gene encodes an adipocyte-associated protein that modulates weight. The objective was to evaluate the role of the rs2289487 genetic variant of the PLIN1 gene on weight loss and glucose metabolism secondary to a partial meal replacement (pMR) hypocaloric diet., Patients and Methods: We conducted an interventional study in 111 postmenopausal obese females with body mass index (BMI) > 35 kg/m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks., Results: After the pMR diet, body weight, (BMI), fat mass, waist circumference, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in these parameters were higher in C allele carriers than in subjects with TT genotype. The percentage of patients who achieved 7.5% weight loss was higher in the C carriers (57.4% vs. 27.6%), (adjusted Odds Ratio 2.14, 95% CI = 1.33-9.40; p = 0.02). The decrease in the percentage of diabetes mellitus or impaired fasting glucose decrease was statistically significant in C allele carriers (30.2% vs. 18.9%; p = 0.01) (OR 0.54, 95% CI = 0.22-0.78; p = 0.02)., Conclusions: The C allele of rs2289487 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement in insulin resistance and the percentage of impaired glucose metabolism.
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- 2023
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33. The Influence of Single Nucleotide Polymorphisms On Body Weight Trajectory After Bariatric Surgery: A Systematic Review.
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Duarte ACS, da Silva NR, Santos Gonçalves VS, Corgosinho FC, de Carvalho KMB, and Horst MA
- Subjects
- Humans, Polymorphism, Single Nucleotide, Risk Factors, Weight Loss genetics, Body Mass Index, Body-Weight Trajectory, Bariatric Surgery, Obesity, Morbid surgery
- Abstract
Purpose of Review: To conduct a systematic review to summarize the results of studies on this subject and to identify whether single nucleotide polymorphisms (SNPs) are good prognostic markers for body weight trajectory after bariatric surgery., Recent Findings: A considerable number of events can influence the body weight trajectory after bariatric surgery, and in the post-genomic era, genetic factors have been explored. This study is registered with PROSPERO (CRD42021240903). SNPs positively associated with poor weight loss after bariatric surgery were rs17702901, rs9939609, rs1360780, rs1126535, rs1137101, rs17782313, rs490683, and rs659366. Alternatively, SNPs rs2229616, rs5282087, rs490683, rs9819506, rs4771122, rs9939609, rs4846567, rs9930506, rs3813929, rs738409, rs696217, rs660339, rs659366, rs6265, rs1801260, and rs2419621 predicted a higher weight loss after bariatric surgery. Six studies performed with a genetic risk score (GRS) model presented significant associations between GRS and outcomes following bariatric surgery. This systematic review shows that, different SNPs and genetic models could be good predictors for body weight trajectory after bariatric surgery. Based on the results of the selected studies for this Systematic Review is possible to select SNPs and metabolic pathways of interest for the GRS construction to predict the outcome of bariatric surgery to be applied in future studies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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34. Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery.
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Gong Y, Wu Q, Huang S, Fu Z, Ye J, Liu R, Lin S, Guan W, Yang N, Li JZ, Liang H, and Zhou H
- Subjects
- Humans, East Asian People, Receptor, Melanocortin, Type 4 genetics, Receptor, Melanocortin, Type 4 metabolism, Weight Loss genetics, Obesity, Morbid genetics, Obesity, Morbid surgery, Bariatric Surgery adverse effects
- Abstract
Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C277X, among which V103I has a relatively high frequency, while other five variants are rare in the population. The prevalence of MC4R carriers in Chinese morbid obese patients (body mass index ≥ 45 kg m
-2 ) is detected as 16.9% in this study. R165W and C277X are loss-of-function variants. The patient with R165W achieves excess weight loss (%EWL) as high as 20.6% and 50.3% at 1 and 8 months after surgery, respectively. G233S is reported for the first time in Asia obese population. The patient harboring G233S has a %EWL as 23.3% one month postsurgery. It is concluded that morbid obese patients with rare MC4R variants can benefit from metabolic surgery. More importantly, the choice of surgery procedure and MC4R variant should be taken into consideration for personalized treatment. In the future, a larger size cohort, accompanied with regular and longer follow-up, would be helpful., (© 2023 Wiley-VCH GmbH.)- Published
- 2023
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35. Implication of DNA methylation during lifestyle mediated weight loss.
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Aurich S, Müller L, Kovacs P, and Keller M
- Subjects
- Humans, Weight Loss genetics, Epigenesis, Genetic, Obesity genetics, DNA Methylation, Life Style
- Abstract
Over the past 50 years, the number of overweight/obese people increased significantly, making obesity a global public health challenge. Apart from rare monogenic forms, obesity is a multifactorial disease, most likely resulting from a concerted interaction of genetic, epigenetic and environmental factors. Although recent studies opened new avenues in elucidating the complex genetics behind obesity, the biological mechanisms contributing to individual's risk to become obese are not yet fully understood. Non-genetic factors such as eating behaviour or physical activity are strong contributing factors for the onset of obesity. These factors may interact with genetic predispositions most likely via epigenetic mechanisms. Epigenome-wide association studies or methylome-wide association studies are measuring DNA methylation at single CpGs across thousands of genes and capture associations to obesity phenotypes such as BMI. However, they only represent a snapshot in the complex biological network and cannot distinguish between causes and consequences. Intervention studies are therefore a suitable method to control for confounding factors and to avoid possible sources of bias. In particular, intervention studies documenting changes in obesity-associated epigenetic markers during lifestyle driven weight loss, make an important contribution to a better understanding of epigenetic reprogramming in obesity. To investigate the impact of lifestyle in obesity state specific DNA methylation, especially concerning the development of new strategies for prevention and individual therapy, we reviewed 19 most recent human intervention studies. In summary, this review highlights the huge potential of targeted interventions to alter disease-associated epigenetic patterns. However, there is an urgent need for further robust and larger studies to identify the specific DNA methylation biomarkers which influence obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aurich, Müller, Kovacs and Keller.)
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- 2023
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36. Weight Loss Is a Strong Predictor of Memory Disorder Independent of Genetic Influences.
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Chen S, Sarasua SM, Davis NJ, DeLuca JM, Thielke SM, and Yu CE
- Subjects
- Humans, Case-Control Studies, Weight Loss genetics, Apolipoproteins E genetics, Memory Disorders genetics, Dementia genetics
- Abstract
Background: Past studies identified a link between weight loss and dementia, but lacked consistent conclusions. We sought to establish this link by examining the weight change profiles before and after dementia diagnosis., Methods: Using data from the Health and Retirement Study (1996-2020), we examined 13,123 participants. We conducted a nested case-control analysis to assess differences in biennial weight change profile while controlling for BMI, longevity polygenic risk scores, and APOE gene variants., Results: Participants with a memory disorder lost weight (-0.63%) biennially, whereas those without a diagnosis did not (+0.013%, p -value < 0.0001). Our case-control study shows a significant difference ( p -value < 0.01) in pre-dementia % weight changes between the cases (-0.29%) and controls (0.19%), but not in post-dementia weight changes. The weight loss group have the highest risk (OR = 2.01; p -value < 0.0001) of developing a memory disorder compared to the stable weight and weight gain groups. The observations hold true after adjusting for BMI, longevity polygenic risk scores, and APOE variant in a multivariable model., Conclusions: We observe that weight loss in dementia is a physiological process independent of genetic factors associated with BMI and longevity. Pre-dementia weight loss may be an important prognostic criterion to assess a person's risk of developing a memory disorder.
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- 2023
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37. The Effect of Heterozygous Gene Variants of the Leptin-Melanocortin Pathway on Weight Loss Following Sleeve Gastrectomy.
- Author
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Feris F, Ghusn W, Campos A, Cifuentes L, De la Rosa A, Sacoto D, Fansa S, Anazco D, Hurtado MD, Bublitz JT, Abu Dayyeh BK, Ghanem OM, Kellogg TA, Olson J, Camilleri M, and Acosta A
- Subjects
- Humans, Gastrectomy, Weight Loss genetics, Retrospective Studies, Treatment Outcome, Leptin genetics, Leptin metabolism, Obesity, Morbid surgery
- Published
- 2023
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38. DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressure in Response to Weight-Loss Diets in the POUNDS Lost Trial.
- Author
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Kou M, Li X, Shao X, Grundberg E, Wang X, Ma H, Heianza Y, Martinez JA, Bray GA, Sacks FM, and Qi L
- Subjects
- Adult, Humans, Blood Pressure genetics, Birth Weight, Weight Loss genetics, Diet, Fat-Restricted, Plasma Membrane Calcium-Transporting ATPases, DNA Methylation, Obesity genetics
- Abstract
Background: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life., Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. We defined the regional DNAm levels as the average methylation level of 5'-cytosine-phosphate-guanine-3' within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793), respectively. Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes., Results: The regional DNAm at LINC00319 , showed significantly different associations with 2-year changes in systolic blood pressure and diastolic blood pressure among participants assigned to low- or high-fat diets ( P for interaction<0.05 for all). In response to the low-fat diet, per SD higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in systolic blood pressure (β, -1.481; P =0.020) and diastolic blood pressure (β, -1.096; P =0.009). Three trajectories of changes in systolic blood pressure or diastolic blood pressure were identified, and participants with higher regional DNAm at LINC00319 were more likely to experience and maintain decreased systolic blood pressure and diastolic blood pressure (odds ratio of being in decrease-stable versus stable [95% CI], 1.542 [1.146-2.076] and 1.463 [1.125-1.902])., Conclusions: Our findings suggest that DNAm could be a metabolic memory bridging early and later life, and an indicator of more benefits from eating a low-fat weight-loss diet., Competing Interests: Disclosures None.
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- 2023
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39. Expression of Adipose Tissue Extracellular Matrix-Related Genes Predicts Weight Loss after Bariatric Surgery.
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Osorio-Conles Ó, Olbeyra R, Vidal J, Ibarzabal A, Balibrea JM, and de Hollanda A
- Subjects
- Humans, Subcutaneous Fat metabolism, Adipose Tissue, Weight Loss genetics, Extracellular Matrix genetics, Collagen metabolism, Diabetes Mellitus, Type 2 metabolism, Bariatric Surgery
- Abstract
Background: We evaluated the association between white adipose tissue parameters before bariatric surgery (BS) and post-surgical weight loss, with an especial focus on extracellular matrix (ECM) gene expression., Methods: Paired samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained from 144 subjects undergoing BS. The association between total body weight loss (%TBWL) at 12 months after BS and the histological characteristics and gene expression of selected genes in SAT and VAT was analyzed., Results: Fat cell area, size-frequency distribution, and fibrosis in SAT or VAT prior to surgery were not associated with %TBWL. On the contrary, the SAT expression of COL5A1 and COL6A3 was associated with %TBWL after BS (both p < 0.001), even after adjusting for age, gender, baseline BMI, and type 2 diabetes status (T2D). Furthermore, in logistic regression analyses, the expression of these genes was significantly associated with insufficient WL (IWL = TBWL < 20%) after BS (respectively, p = 0.030 and p = 0.031). Indeed, in ROC analysis, the prediction of IWL based on sex, age, BMI, T2D, and the type of surgery (AUC = 0.71) was significantly improved with the addition of SAT- COL5A1 gene expression (AUC = 0.88, Z = 2.13, p = 0.032)., Conclusions: Our data suggest that the expression of SAT ECM-related genes may help explain the variability in TBWL following BS.
- Published
- 2023
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40. Pharmacogenetic interactions of medications administered for weight loss in adults: a systematic review and meta-analysis.
- Author
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BouSaba J, Vosoughi K, Dilmaghani S, Prokop LJ, and Camilleri M
- Subjects
- Adult, Humans, Pharmacogenetics, Naltrexone therapeutic use, Bupropion therapeutic use, Peptides therapeutic use, Venoms therapeutic use, Glucagon-Like Peptide 1 genetics, Glucagon-Like Peptide 1 therapeutic use, Weight Loss genetics, Glucagon-Like Peptide-1 Receptor genetics, Protein Serine-Threonine Kinases, Hypoglycemic Agents therapeutic use, Diabetes Mellitus, Type 2 drug therapy
- Abstract
Aim: To analyze roles of single nucleotide variants (SNVs) on weight loss with US FDA-approved medications. Materials & methods: We searched the literature up until November 2022. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Results: 14 studies were included in qualitative analysis and seven in meta-analysis. SNVs in CNR1 , GLP-1R , MC4R , TCF7L2 , CTRB1/2 , ADIPOQ , SORCS1 and ANKK1 were evaluated relative to weight loss with glucagon-like peptide-1 agonists (13 studies) or naltrexone-bupropion (one study). CNR1 gene (rs1049353), GLP-1R gene (rs6923761, rs10305420), TCF7L2 gene (rs7903146) were associated with weight loss in at least one study involving glucagon-like peptide-1 agonist(s). The meta-analysis did not identify any consistent effect of SNVs. Conclusion: Pharmacogenetic interactions for exenatide, liraglutide, naltrexone-bupropion and weight loss were identified, but the directionality was inconsistent.
- Published
- 2023
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41. Effects of Heterozygous Variants in the Leptin-Melanocortin Pathway on Transoral Outlet Reduction After Roux-en-Y Gastric Bypass: A Case-Control Study and Review of Literature.
- Author
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Gala K, Ghusn W, Fansa S, Abu Dayyeh BK, Ghanem OM, Kellogg T, and Acosta A
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Body Mass Index, Case-Control Studies, Leptin, Reoperation, Retrospective Studies, Suture Techniques, Treatment Outcome, Weight Gain, Weight Loss genetics, Melanocortins, Gastric Bypass methods, Obesity, Morbid surgery
- Abstract
Background: Transoral outlet reduction (TORe) is a safe and effective technique for management of weight regain (WR) after Roux-en-Y Gastric Bypass (RYGB). Carriers of a heterozygous variant in the leptin melanocortin pathway (LMP) have been shown to be at high risk for WR in the mid- and long-term after RYGB. Our case series includes four patients with heterozygous LMP variants and presents novel data on their weight loss after TORe., Methods: We performed a retrospective study of the Mayo Clinic Biobank and identified adult participants who had been genotyped and found to have or do not have a heterozygous variant in the LMP ("carriers" vs "non-carriers", respectively) and had undergone a TORe procedure. TBWL% at 1, 3, 6, 9, and 12 months ± 15 days were calculated based on baseline weight at TORe procedure., Results: A total of 14 patients were included in the analysis: four patients (mean age 51.0 [5.2] years, 100% females, body mass index [BMI] 40.5 [8.7] kg/m
2 ) with LMP variant and 10 non-carriers (age 55.4 [15.3] years, 90% females, BMI 37.3 [7.7] kg/m2 ). There were no baseline differences between carriers and non-carriers at time of TORe procedure. After TORE, carriers lost less weight when compared to non-carriers at 3, 6, 9, and 12 months. The difference at 12 months was statistically significant (1.6 vs 12.3%; p = 0.03)., Conclusions: Patients with a LMP variant and that underwent RYGB showed decreased weight loss after undergoing TORe. Further and larger studies are needed to comprehend the effect of TORe on patients with LMP variants., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
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42. Baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss in individuals with obesity.
- Author
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Oghabian A, van der Kolk BW, Marttinen P, Valsesia A, Langin D, Saris WH, Astrup A, Blaak EE, and Pietiläinen KH
- Subjects
- Humans, Subcutaneous Fat metabolism, Weight Loss genetics, Gene Expression genetics, Lipids, Obesity genetics, Diet, Reducing
- Abstract
Background: Weight loss effectively reduces cardiometabolic health risks among people with overweight and obesity, but inter-individual variability in weight loss maintenance is large. Here we studied whether baseline gene expression in subcutaneous adipose tissue predicts diet-induced weight loss success., Methods: Within the 8-month multicenter dietary intervention study DiOGenes, we classified a low weight-losers (low-WL) group and a high-WL group based on median weight loss percentage (9.9%) from 281 individuals. Using RNA sequencing, we identified the significantly differentially expressed genes between high-WL and low-WL at baseline and their enriched pathways. We used this information together with support vector machines with linear kernel to build classifier models that predict the weight loss classes., Results: Prediction models based on a selection of genes that are associated with the discovered pathways 'lipid metabolism' (max AUC = 0.74, 95% CI [0.62-0.86]) and 'response to virus' (max AUC = 0.72, 95% CI [0.61-0.83]) predicted the weight-loss classes high-WL/low-WL significantly better than models based on randomly selected genes ( P < 0.01). The performance of the models based on 'response to virus' genes is highly dependent on those genes that are also associated with lipid metabolism. Incorporation of baseline clinical factors into these models did not noticeably enhance the model performance in most of the runs. This study demonstrates that baseline adipose tissue gene expression data, together with supervised machine learning, facilitates the characterization of the determinants of successful weight loss., Competing Interests: At the time of the study, Armand Valsesia was a full-time employee at Nestlé Institute of Health Sciences SA. W. H. Saris discloses the receipt of research support from several food companies such as Nestlé, DSM, Unilever, Nutrition et Sante and Danone as well as pharmaceutical companies including GSK, Novartis and Novo Nordisk; he is also an unpaid scientific advisor for the International Life Science Institute (ILSI) Europe. Arne Astrup discloses grants and personal fees received from Gelesis, USA; personal fees from Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Groupe Éthique et Santé, France; IKEA Food Scientific Health Advisory Board, SE; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Pfizer, USA; Saniona, DK; Weight Watchers, USA & Zaluvida, Switzerland; and grants from DC-Ingredients Denmark, which lie beyond the scope of the work reported here. Ellen E. Blaak received financial support from food industry, such as DSM, Danone, Friesland Campina, Avebe and Sensus, partly within the context of public–private consortia and has received funding from pharmaceutical companies including Novartis. She is involved in several task forces and expert groups related to ILSI Europe.g interests., (© 2023 Oghabian et al.)
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- 2023
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43. Role of resistin (rs7139228) gene polymorphism with metabolic response after a hypocaloric mediterranean diet.
- Author
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de Luis DA, Primo D, Izaola O, and Aller R
- Subjects
- Humans, Resistin genetics, Diet, Reducing, Polymorphism, Single Nucleotide, Obesity epidemiology, Obesity genetics, Insulin, Weight Loss genetics, Triglycerides, Metabolic Syndrome epidemiology, Metabolic Syndrome genetics, Diet, Mediterranean, Insulin Resistance genetics, Hyperglycemia
- Abstract
Background: The SNP (rs7139228) of the RETN gene is a polymorphism that has been associated with metabolic disorder in subjects with obesity, and its effect on metabolic response after dietary intervention has not been evaluated., Objective: Our objective was to analyse the effects of the polymorphism of the RETN gene rs7139228 on metabolic changes secondary to weight loss with a hypocaloric Mediterranean diet., Design: 1000 obese Caucasian patients were evaluated. An anthropometric evaluation and a biochemical analysis were performed before and after 12 weeks of a hypocaloric Mediterranean diet. The statistical analysis was performed as a dominant model (GG vs GA+AA)., Results: Improvements in anthropometric parameters, leptin levels and systolic blood pressure were similar in both genotype groups. In non- A allele carriers, levels of resistin, insulin, HOMA-IR, triglycerides and C-reactive protein decreased. The improvements were statistically significant in this group; resistin (-1.3+0.1ng/dL: p=0.02), triglycerides (-22.9+4.9mg/dl: p=0.02), CRP (-2.7+0 0.4mg/dl: p=0.02), insulin -6.5+1.8 mIU/L: p=0.02) and HOMA-IR (-2.2+0.8: p=0, 03). In addition, insulin, HOMA-IR and resistin levels were higher in A allele carriers than in non-carriers. Finally, the prevalence of metabolic syndrome and hyperglycaemia were higher in A allele carriers, and these percentages only decreased after intervention in non-A allele carriers., Conclusion: The A rs7139228 allele is associated with a worse metabolic response (insulin, HOMA-IR, triglycerides and CRP) after weight loss with a hypocaloric Mediterranean diet. A non-significant decrease in the prevalence of metabolic syndrome and hyperglycaemia were detected in A allele carriers., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2023
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44. MicroRNAs and Diet-induced Weight Loss: What's the Link?
- Author
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Cannataro R, Abrego-Guandique DM, Caroleo MC, Bonilla DA, and Cione E
- Subjects
- Humans, Obesity genetics, Diet, Reducing, Weight Loss genetics, Adipose Tissue, MicroRNAs genetics
- Abstract
It is now well established that lifestyle, particularly eating habits, modulates the synthesis and action of microRNAs (miRNAs). In particular, several nutritional schemes have proven effective in improving body composition, but molecular mechanisms still need to be fully understood. Within the complex physiological network of food intake regulation, it is essential to understand the changes in endocrine activity after the reduction of adipose tissue during a weight loss program. This could be the key to identifying the optimal endocrine profile in high responders, the assessment of musculoskeletal status, and long-term management. In this review, we summarize the state of the art regarding miRNAs as a function of weight loss and as a mechanistic regulator of the effectiveness of the nutritional program., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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45. Bariatric surgery-induced weight loss and associated genome-wide DNA-methylation alterations in obese individuals.
- Author
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Talukdar FR, Escobar Marcillo DI, Laskar RS, Novoloaca A, Cuenin C, Sbraccia P, Nisticò L, Guglielmi V, Gheit T, Tommasino M, Dogliotti E, Fortini P, and Herceg Z
- Subjects
- Humans, Infant, Epigenesis, Genetic, DNA Methylation, Obesity genetics, Obesity surgery, Diet, Reducing, Weight Loss genetics, DNA, Obesity, Morbid genetics, Bariatric Surgery
- Abstract
Background: Obesity is a multifactorial and chronic condition of growing universal concern. It has recently been reported that bariatric surgery is a more successful treatment for severe obesity than other noninvasive interventions, resulting in rapid significant weight loss and associated chronic disease remission. The identification of distinct epigenetic patterns in patients who are obese or have metabolic imbalances has suggested a potential role for epigenetic alterations in causal or mediating pathways in the development of obesity-related pathologies. Specific changes in the epigenome (DNA methylome), associated with metabolic disorders, can be detected in the blood. We investigated whether such epigenetic changes are reversible after weight loss using genome-wide DNA methylome analysis of blood samples from individuals with severe obesity (mean BMI ~ 45) undergoing bariatric surgery., Results: Our analysis revealed 41 significant (Bonferroni p < 0.05) and 1169 (false discovery rate p < 0.05) suggestive differentially methylated positions (DMPs) associated with weight loss due to bariatric surgery. Among the 41 significant DMPs, 5 CpGs were replicated in an independent cohort of BMI-discordant monozygotic twins (the heavier twin underwent diet-induced weight loss). The effect sizes of these 5 CpGs were consistent across discovery and replication sets (p < 0.05). We also identified 192 differentially methylated regions (DMRs) among which SMAD6 and PFKFB3 genes were the top hypermethylated and hypomethylated regions, respectively. Pathway enrichment analysis of the DMR-associated genes showed that functional pathways related to immune function and type 1 diabetes were significant. Weight loss due to bariatric surgery also significantly decelerated epigenetic age 12 months after the intervention (mean = - 4.29; p = 0.02)., Conclusions: We identified weight loss-associated DNA-methylation alterations targeting immune and inflammatory gene pathways in blood samples from bariatric-surgery patients. The top hits were replicated in samples from an independent cohort of BMI-discordant monozygotic twins following a hypocaloric diet. Energy restriction and bariatric surgery thus share CpGs that may represent early indicators of response to the metabolic effects of weight loss. The analysis of bariatric surgery-associated DMRs suggests that epigenetic regulation of genes involved in endothelial and adipose tissue function is key in the pathophysiology of obesity., (© 2022. The Author(s).)
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- 2022
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46. Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions.
- Author
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Salazar-Valencia IG, Villamil-Ramírez H, Barajas-Olmos F, Guevara-Cruz M, Macias-Kauffer LR, García-Ortiz H, Hernández-Vergara O, Díaz de Sandy-Galán DA, León-Mimila P, Centeno-Cruz F, González-Salazar LE, Guizar-Heredia R, Pichardo-Ontiveros E, Jacobo-Albavera L, Posadas-Sánchez R, Vargas-Alarcón G, Velazquez-Cruz R, Gutiérrez-Aguilar R, Zerrweck C, Rocha-González HI, Reyes-García JG, Carrasco-Portugal MDC, Flores-Murrieta FJ, Tovar AR, Orozco L, Villarreal-Molina T, and Canizales-Quinteros S
- Subjects
- Adult, Humans, Mutation, Obesity genetics, Obesity surgery, Weight Loss genetics, Bariatric Surgery, Phentermine, Receptor, Melanocortin, Type 4 genetics
- Abstract
The loss of function melanocortin 4-receptor ( MC4R ) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.
- Published
- 2022
- Full Text
- View/download PDF
47. The sex-specific influence of FTO genotype on exercise intervention for weight loss in adult with obesity.
- Author
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Wang W, Yang K, Wang S, Zhang J, Shi Y, Zhang H, Jin D, Gu R, Zeng Q, and Hua Q
- Subjects
- Adult, Male, Female, Humans, Body Mass Index, Obesity genetics, Obesity therapy, Genotype, Exercise Therapy, Polymorphism, Single Nucleotide, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Weight Loss genetics
- Abstract
The impact of exercise on weight loss varies significantly among individuals, and genes play a critical role. This study aims to explore whether the FTO gene variant (rs8050136) affects the influence of exercise on weight. The study initially recruited 240 Han Chinese adults with obesity, and 178 of them (101 men, 77 women, aged from 21 to 60) completed a 12-week moderate aerobic exercise programme. The participants were genotyped and obesity-related data were collected before and after the intervention. The intensity and the amount of exercise were precisely monitored. After the intervention, most obesity-related parameters of the participants showed a significant decrease. For muscle and lean body mass, significant change was only observed in males ( P < 0.001) but not females ( P = 0.205, P = 0.200 respectively). Importantly, for weight and BMI loss, we observed a genotype-by-gender interaction ( P = 0.041, P = 0.042 respectively, adjusted for age, exercise time and baseline value). In the further analysis, after stratified for gender, the exercise-induced weight loss ( P = 0.008), BMI loss ( P = 0.010), muscle mass loss ( P = 0.005) and lean body mass loss ( P = 0.004) showed greater decrease in male subjects carrying at least one A allele compared to non-carriers. In conclusion, our study suggests that in Han Chinese population with obesity, carrying "obese risk gene" FTO (rs8050136) does not lead to the resistance to weight management intervention. More importantly, in male subjects, carrying FTO risk allele would even lose more weight than non-carriers after exercise intervention. Highlights For Han Chinese adults with obesity, carrying "obese risk gene" FTO could still achieve weight loss through exercise.Males carrying FTO risk allele would lose more weight than non-carriers after a 12-weeks exercise programme.
- Published
- 2022
- Full Text
- View/download PDF
48. Combination of Single-Nucleotide Polymorphisms and Preoperative Body Mass Index to Predict Weight Loss After Laproscopic Sleeve Gastrectomy in Chinese Patients with Body Mass Index ≥ 32.5 kg/m 2 .
- Author
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Wang L, Xu G, Tian C, Sang Q, Yu C, Wuyun Q, Wang Z, Chen W, Amin B, Wang D, Chen G, Lian D, and Zhang N
- Subjects
- Humans, Body Mass Index, Polymorphism, Single Nucleotide, Retrospective Studies, Gastrectomy, Weight Loss genetics, Obesity surgery, China epidemiology, Treatment Outcome, Obesity, Morbid surgery, Gastric Bypass, Laparoscopy
- Abstract
Background: Single-nucleotide polymorphisms (SNPs) associated with obesity predict laparoscopic Roux-en-Y gastric bypass (LRYGB) and biliopancreatic diversion with duodenal switch (BPD/DS) for weight loss with good efficiency. However, prediction of weight loss after laparoscopic sleeve gastrectomy using SNPs has not been well investigated., Objectives: To predict weight loss after laparoscopic sleeve gastrectomy using obesity-related SNPs and clinical variants in Chinese patients with body mass index (BMI) ≥ 32.5 kg/m
2 ., Methods: We detected 29 SNPs. Binary logistic regression was used to screen SNPs and clinical variables with predictive value. Receiver operating characteristic (ROC) curves were plotted for clinical variables, SNPs, and their combination, and areas under the ROC curve (AUC) were compared. Internal and external validation tests were performed., Results: rs12535708, rs651821, and rs5082 were constructed as the genetic risk score (GRS). Preoperative BMI was constructed as the clinical risk score (CRS). Preoperative BMI and SNPs were constructed as the cumulative genetic risk score (CGRS). ROC curves of GRS, CRS, and CGRS showed that the optimal cutoffs were 0.831 (AUC = 0.840; sensitivity, 92.96%; specificity, 64.29%), 43.46 kg/m2 (AUC = 0.830; sensitivity, 76.06%; specificity, 85.71%), and 0.921 (AUC = 0.931; sensitivity, 77.46%; specificity, 92.86%), respectively. The AUC of CGRS was significantly greater than that of CRS (P < 0.05) and greater than GRS without statistical significance., Conclusion: In Chinese patients with BMI ≥ 32.5 kg/m2 , GRS and CRS could predict weight loss success. However, CGRS was superior to GRS or CRS alone., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2022
- Full Text
- View/download PDF
49. FTO variant RS 1121980 interact with metabolic response after weight loss with a meal replacement hypocaloric diet in Caucasian obese subjects.
- Author
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de Luis DA, Izaola O, Primo D, and Lopez JJ
- Subjects
- Humans, Diet, Reducing methods, Polymorphism, Single Nucleotide, Weight Loss genetics, Insulin, Genotype, Triglycerides, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Obesity metabolism, Insulin Resistance genetics
- Abstract
Objective: One genetic variant (rs1121980) of FTO gene has been related with body mass index and visceral adiposity. The objective of our study was to investigate the role of rs1121980 genetic variant of FTO gene on weight loss and metabolic changes secondary to a partial meal replacement (pMR) hypocaloric diet., Patients and Methods: We conducted an interventional study on 219 obese Caucasian subjects with body mass index (BMI) > 30 kg/m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks. Adiposity and biochemical parameters (lipid profile, insulin, homeostasis model assessment (HOMA-IR) and glucose) were determined., Results: After the pMR diet, body weight, BMI, fat mass, waist circumference, blood pressure, total-cholesterol, LDL-cholesterol, triglyceride, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in adiposity parameters and some biochemical parameters (insulin, HOMA-IR, triglyceride levels) were bigger in non-T allele carriers than in T allele carriers. The percentage of patients who achieved 7.5% weight loss was higher in the non-T carriers (76.7% vs. 48.4%), also with a different average of weight loss (-12.3±0.3 kg vs. -5.9±0.5 kg: p=0.01). The odds ratio to achieve 7.5% of weight loss was (OR= 2.22, 95% CI=1.24-4.01; p=0.02)., Conclusions: Non-T allele carriers of rs1121980 show a higher magnitude of weight loss and improvement in adiposity parameters, insulin, HOMA-IR and triglyceride levels resulting from a pMR diet than T allele carriers.
- Published
- 2022
- Full Text
- View/download PDF
50. Weight loss reduces circulating micro-RNA related to obesity and breast cancer in postmenopausal women.
- Author
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Duggan C, Tapsoba JD, Scheel J, Wang CY, and McTiernan A
- Subjects
- Humans, Female, Overweight complications, Overweight genetics, Postmenopause, DNA Methylation, Weight Loss genetics, Obesity complications, Obesity genetics, Circulating MicroRNA, Breast Neoplasms genetics, MicroRNAs genetics
- Abstract
Postmenopausal women with overweight or obesity have an increased risk of developing breast cancer but many of the mechanisms underlying this association remain to be elucidated. MicroRNAs (miRNAs), short non-coding single-stranded RNAs, regulate many physiological processes by controlling post-transcriptional regulation of mRNA. We measured circulating miRNA from 192 overweight/obese postmenopausal women (50-75 years) who were part of a randomized controlled trial, comparing independent and combined effects of a 12-month reduced-calorie weight-loss diet and exercise programme, versus control. RNA was extracted from stored plasma samples, and 23 a priori selected miRNA targets related to aetiology of breast cancer or obesity were measured using NanoString nCounter miRNA Expression assays. Changes from baseline to 12-months between controls and women in the diet/exercise weight loss arms were analysed using generalized estimating equations modification of linear regression, adjusted for confounders. We next examined changes in levels of circulating miRNA by amount of weight loss (0-10% versus ≥10%). Participants randomized to weight-loss interventions had statistically significantly greater reductions in miR-122 (-7.25%), compared to controls (+ 33.5%, P = 0.009), and miR-122 levels were statistically significantly correlated with weight loss (rho = 0.24; P = 0.001) Increasing weight loss was associated with greater reductions in miR-122 vs. controls (-11.7% (≥10% weight loss); +2.0% (0-10% weight loss) +33.5% (controls); P
trend = 0.006), though this was not significant after correction for multiple testing (P = 0.05/23) Our study supports the effect of weight loss on regulation of miRNA.- Published
- 2022
- Full Text
- View/download PDF
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