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Objective: Time-restricted eating (TRE), a dietary approach that confines food intake to specific time windows, has shown metabolic benefits. However, its impact on body weight loss remains inconclusive. The objective of this study was to investigate the influence of early TRE (eTRE) and delayed TRE (dTRE) on fat mobilization using human adipose tissue (AT) cultures., Methods: Subcutaneous AT was collected from 21 participants with severe obesity. We assessed fat mobilization by measuring glycerol release in AT culture across four treatment conditions: control, eTRE, dTRE, and 24-h fasting., Results: TRE had a significant impact on lipolysis (glycerol release [mean (SD)] in micromoles per hour per gram: control, 0.05 [0.003]; eTRE, 0.10 [0.006]; dTRE, 0.08 [0.005]; and fasting, 0.17 [0.008]; p < 0.0001). Both eTRE and dTRE increased lipolysis compared with the control group, with eTRE showing higher glycerol mobilization than dTRE during the overall 24-h time window, especially at the nighttime/habitual sleep episode (p < 0.0001). Further analysis of TRE based on fasting duration revealed that, independently of the time window, glycerol release increased with fasting duration (in micromoles per hour per gram: 8 h = 0.08 [0.001]; 12 h = 0.09 [0.008]; and 16 h of fasting = 0.12 [0.011]; p < 0.0001)., Conclusions: This study provides insights into the potential benefits of TRE on fat mobilization and may guide the design of future dietary strategies for weight management and metabolic health., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Objectives: Bariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome., Methods: We characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models., Results: There were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate., Conclusions: Our findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown. We investigated the effects of ghrelin infusion on appetite and glucose tolerance in individuals with obesity before and 3 mo after SG. Twelve participants scheduled for SG were included. Before and 3 mo after surgery, a mixed-meal test followed by an ad libitum meal test was performed with concomitant infusions of acyl-ghrelin (1 pmol/kg/min) or placebo. Infusions began 60 min before meal intake to reach a steady state before the mixed-meal and were continued throughout the study day. Two additional experimental days with 0.25 pmol/kg/min and 10 pmol/kg/min of acyl-ghrelin infusions were conducted 3 mo after surgery. Both before and after SG, postprandial glucose concentrations increased dose dependently during ghrelin infusions compared with placebo. Ghrelin infusions inhibited basal and postprandial insulin secretion rates, resulting in lowered measures of β-cell function, but no effect on insulin sensitivity was seen. Ad libitum meal intake was unaffected by the administration of ghrelin. In conclusion, ghrelin infusion increases postprandial plasma glucose concentrations and impairs β-cell function before and after SG but has no effect on ad libitum meal intake. We speculate that the lower concentration of ghrelin after SG may impact glucose metabolism following this procedure. NEW & NOTEWORTHY Ghrelin's effect on glucose tolerance and food intake following sleeve gastrectomy (SG) was evaluated. Acyl-ghrelin was infused during a mixed-meal and ad libitum meals before and 3 mo after surgery. Postprandial glucose concentrations increased during ghrelin infusions, both before and after surgery, while insulin production was inhibited. However, ad libitum meal intake did not differ during ghrelin administration compared with placebo. The decreased ghrelin concentration following SG may contribute to the glycemic control after surgery.

Metabolic bariatric surgery remains the most effective and durable treatment for severe obesity. Women of reproductive age represent the largest demographic group undergoing these procedures. Metabolic bariatric surgery can have both beneficial and adverse effects on pregnancy outcomes. One of the most common adverse effects is fetal growth restriction. To mitigate these adverse effects, it is crucial to explore lifestyle modifications aimed at promoting a healthy pregnancy. Modifiable factors during pregnancy after metabolic bariatric surgery include the amount of gestational weight gain. The aim of this comprehensive review is to provide an overview of what is known about gestational weight gain in pregnancy after bariatric metabolic surgery. This review is focused on the two most performed procedures: sleeve gastrectomy and Roux-en-Y gastric bypass.

Aim: To validate the Individualized Metabolic Surgery (IMS) score and assess long-term remission of type 2 diabetes (T2D) after duodenal switch (DS)-type procedures in patients with obesity. In addition, to help guide metabolic procedure selection for those patients categorized as having severe T2D., Materials and Methods: This is a retrospective single cohort study of all patients with T2D and severe obesity, who underwent DS-type procedures at a single institution from December 2010 to December 2018. Study endpoints included validating the IMS score in our cohort and evaluating the impact of DS-type procedures on long-term (≥ 5 years) remission of T2D, especially in patients with severe disease. A receiver operator characteristic curve was used to assess the accuracy of the IMS score using the area under the curve (AUC)., Results: The study cohort included 30 patients with complete baseline and long-term glycaemic data after their index DS-type surgery. Twelve patients (40%) were classified with severe T2D, and the distribution of IMS-based severity groups was similar between our cohort and the original IMS study (P = .42). IMS scores predicted long-term T2D remission with AUC = 0.77. Patients with IMS-based severe diabetes achieved significantly higher long-term remission after DS-type procedures compared with gastric bypass and/or sleeve gastrectomy from the original IMS study (42% vs. 12%; P < .05)., Conclusions: The IMS score properly classifies the severity of T2D in our study cohort and adequately predicts its long-term remission after DS-type procedures. While T2D remission decreases with more severe IMS scores, long-term remission remains high after DS-type procedures among patients with severe disease., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Several studies have indicated that miRNAs play crucial roles in adipogenesis, insulin resistance, and inflammatory pathways associated with obesity and change after metabolic bariatric surgery (MBS). This systematic review explores and maps the existing literature on how miRNAs are expressed and investigates the unique miRNAs with the effects after MBS. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and EMBASE were searched from 2019 until February 2024. This SR found 825 miRNAs from 25 studies, identifying 507 unique ones not used twice in the same study. A total of 21 studies (84%) measured RNA before and after surgery. The miRNA used per study ranged from 1 to 146 miRNA types, with a median study sample size of just 27 patients per study, raising concerns about some conclusions' robustness. From the 507 unique miRNAs, only 16 were consistently analyzed in 4 to 7 studies, which gave 77 different outcomes in relation to miRNA after MBS. MiRNA 122 and 122-5p were analyzed the most. Others were 106b-5p, 140-5p, 183-5p, 199b-5p, 20b-5p, 424-5p, 486-5p, 7-5p, 92a, 93-5p, 194-5p, 21-5p, 221, 320a, and 223-3p. A gap was observed in many studies, whereby the results were not the same, or there was no explanation for the effects after MBS was given within the same miRNA. Fifteen miRNAs were reported to have the same upward and downward trend, although not within the same study, and only 26.1% employed some form of statistical modeling to account for bias or confounding factors. Directions and effects in miRNA are visible, but still, inconsistent outcomes linked to the same miRNA after MBS, underscoring the need for clarity in miRNA-outcome relationships. Collaborative efforts, consensus-driven miRNA dictionaries, and larger, more rigorous studies are necessary to improve methodology designs and improve outcomes., (© 2024. The Author(s).)

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects ( p < 0.001, respectively). Ob-Rb was decreased ( p < 0.001), whereas Sam68 was increased ( p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.

Background: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP., Methods: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored., Results: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF., Conclusion: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP., (© 2024. The Author(s).)

Background and Objectives: Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations., Methods: Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations., Results: Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R 2  = 0.466, and mean bias of 23 kcal/day., Conclusion: This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth., (© 2024 World Obesity Federation.)

Purpose: Obesity, defined as abnormal or excessive fat accumulation that presents a risk to health, rose from 8.6 to 10.5% in Singapore's residents. Bariatric surgery, the primary treatment for severe obesity, induces fat and muscle loss. Adequate protein intake is vital for preventing muscle loss. This study examines nitrogen balance in individuals with obesity pre- and post-surgery., Materials and Methods: Sixteen participants with severe obesity (BMI ≥ 32.5 kg/m 2 ) undergoing bariatric surgery (14 sleeve gastrectomy, 2 Roux-en-Y gastric bypass) and 20 normal-weight controls (BMI < 25 kg/m 2 ) were recruited. Nitrogen balance, calculated from dietary protein intake and urine nitrogen excretion, was assessed. Participants with obesity were re-evaluated 6 months post-surgery. Data were analyzed using parametric methods., Results: At baseline, controls had a BMI of 20.8 ± 2.1 kg/m 2 ; those with obesity had 40.9 ± 7.3. Daily calorie and protein intake for participants with obesity were not statistically significantly different from controls (calorie intake at 1467 ± 430 vs. 1462 ± 391 kcal, p = 0.9701, protein intake 74.2 ± 28.7 vs. 64.6 ± 18.3 g, p = 0.2289). Post-surgery, BMI, fat-free mass, fat mass, total energy intake, carbohydrate, and protein intake decreased significantly (p < 0.01). Protein oxidation and urine nitrogen excretion did not change after bariatric surgery. However, nitrogen balance significantly reduced from 2.62 ± 5.07 to - 1.69 ± 5.07 g/day (p = 0.025)., Conclusion: Dietary protein intake is inadequate in individuals with obesity at 6 months post-bariatric surgery and contributes to a state of negative nitrogen balance., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Objective: Both Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are effective at inducing weight loss, but more information is needed on their comparative effectiveness at improving clinical/biochemical outcomes related to the presence of hyperlipidemia, metabolic dysfunction-associated steatotic liver disease (MASLD), or type 2 diabetes (T2D) at baseline. Here we aimed to assess this in real-world practice., Methods: This is a prospective cross-sectional and cohort study of 142 patients who underwent RYGB or LSG as per clinical practice. Clinical/biochemical data were collected at baseline, prior to surgery and 12 months post-bariatric surgery. Liver biopsy was performed during surgery to diagnose MASLD. The main outcome was 12-month changes in lipid parameters, mainly total cholesterol, between types of surgery., Results: A TOTAL OF: 107 participants underwent RYGB and 35 underwent LSG. Both groups were similar at baseline except for a higher proportion of males and waist circumference in the LSG group. At 12 months postsurgery, RYGB versus LSG resulted in a significantly lower body mass index, triglycerides, total cholesterol, and low-density lipoprotein. However, alanine aminotransferase was significantly lower in those who underwent LSG. In subgroup analyses RYGB was superior at improving lipid-related parameters in those with hyperlipidemia, whereas LSG was superior at reducing alanine aminotransferase in those with MASLD., Conclusions: RYGB versus LSG leads to greater reductions in body mass index and lipid parameters, especially in those with hyperlipidemia, whereas LSG showed greater improvements in liver enzymes in those with MASLD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: J. Allard reports financial support was provided by Canadian Institutes of Health Research. A. Okrainec reports a relationship with Ethicon and Medtronic that includes: speaking and lecture fees., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM after bariatric surgery. Inclusion criteria were subjects 18 to 65 years of age with morbid obesity undergoing bariatric surgery. All data were measured before and 6 and 12 months after surgery. The study included 104 subjects: women/men: 83/21; mean age 43.1 (SD 8.4) years; BMI: 38.8 kg/m 2 (SD 3.8). Surgery with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) was performed in 84 (81%) and 20 (19%) subjects, respectively. From before to 6-12 months after surgery, procollagen type 1 N-terminal propeptid (P1NP) increased by 45.6 µg/L (95% CI 41.5-50.0, p < 0.001), and alkaline phosphatase (ALP) by 10 U/L (95% CI 7-14, p < 0.001). The increases were significantly larger after RYGB than after SG. The APOE- Ɛ3 allele was associated with low levels of BTM and high levels of leptin. There was an unfavourable increase in BTM after bariatric surgery. SG compared to RYGB and the presence of the APOE-Ɛ3 allele were associated with less unfavourable effects. The study emphasises the importance of optimal prophylactic interventions after bariatric surgery to prevent osteoporosis., (© 2024. The Author(s).)

BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.

The determination of energy requirements in clinical practice is based on basal metabolic rate (BMR), frequently predicted by equations that may not be suitable for individuals with severe obesity. This systematic review and meta-analysis examined the accuracy and precision of BMR prediction equations in adults with severe obesity. Four databases were searched in March 2021 and updated in May 2023. Eligible studies compared BMR prediction equations with BMR measured by indirect calorimetry. Forty studies (age: 28-55 years, BMI: 40.0-62.4 kg/m 2 ) were included, most of them with a high risk of bias. Studies reporting bias (difference between estimated and measured BMR) were included in the meta-analysis (n = 20). Six equations were meta-analyzed: Harris & Benedict (1919); WHO (weight) (1985); Owen (1986); Mifflin (1990); Bernstein (1983); and Cunningham (1980). The most accurate and precise equations in the overall analysis were WHO (-12.44 kcal/d; 95%CI: -81.4; 56.5 kcal/d) and Harris & Benedict (-18.9 kcal/d; 95%CI -73.2; 35.2 kcal/d). All the other equations tended to underestimate BMR. Harris & Benedict and WHO were the equations with higher accuracy and precision in predicting BMR in individuals with severe obesity. Additional analyses suggested that equations may perform differently according to obesity BMI ranges, which warrants further investigation., (© 2024 World Obesity Federation.)

One-anastomosis gastric bypass (OAGB) has gained importance as a simple, safe, and effective operation to treat morbid obesity. We previously found that Roux-en-Y gastric bypass surgery with a long compared with a short biliopancreatic limb (BPL) leads to improved weight loss and glucose tolerance in obese mice. However, it is not known whether a long BPL in OAGB surgery also results in beneficial metabolic outcomes. Five-week-old male C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks underwent OAGB surgery with defined BPL lengths (5.5 cm distally of the duodenojejunal junction for short and 9.5 cm for long BPL), or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota, and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14 , and an improved glucose tolerance on day 35 after surgery. Moreover, a long BPL resulted in reduced total cholesterol, while there were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease (MASLD) and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal (HPA) axis and aldosterone were present in the long BPL group. With both the short and long BPL, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial Desulfovibrionaceae and Erysipelotrichaceae and simultaneous increase in Akkermansiaceae , Sutterellaceae , and Enterobacteriaceae . In summary, OAGB surgery with a long compared with a short BPL led to similar weight loss, but improved glucose metabolism, lipid, and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery. NEW & NOTEWORTHY Weight loss following OAGB surgery in obese mice was not influenced by BPL length, but a longer BPL was associated with improved metabolic outcomes, including glucose and lipid homeostasis. These changes could be mediated by bile acids upon altered gut microbiota. Further validation of these findings is required through a randomized human study.

Purpose: To clarify the relationships between the changes in hepatokines and weight loss, and between these changes and the metabolic effects, and the roles played by these changes, after laparoscopic sleeve gastrectomy (LSG)., Methods: We recruited 25 Japanese patients with severe obesity, who underwent LSG. We measured two hepatokines: selenoprotein P (SeP) and leukocyte cell-derived chemotaxin 2 (LECT2), at the baseline, and then 6 months and 1 year after LSG. Finally, we compared the changes in the hepatokines with the parameters of type 2 diabetes (T2D) and non-alcoholic steatohepatitis (NASH)., Results: Changes in LECT2 were correlated with the percentage of total weight loss (ρ = - 0.499, P = 0.024) and the decrease in total fat area (ρ = 0.559, P = 0.003). The changes in SeP were correlated with those in hemoglobin A1c (ρ = 0.526, P = 0.043) and the insulinogenic index (ρ = 0.638, P = 0.010) in T2D patients. In patients with NASH, the LECT2 levels were correlated with liver steatosis (ρ = 0.601)., Conclusions: SeP levels decrease in association with HbA1c reduction, whereas LECT2 levels are associated with reductions in fat mass and NASH scores after LSG. Hepatokines may be involved in the pathology of obesity and its complications., (© 2023. The Author(s).)

Purpose of Review: Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility., Recent Findings: Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility., Summary: Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bariatric surgery is an effective treatment for morbid obesity. However, a subset of individuals seeking bariatric surgery may exhibit a metabolically healthy obesity (MHO) phenotype, suggesting that they may not experience metabolic complications despite being overweight., Objective: This study aimed to determine the prevalence and metabolic features of MHO in a population undergoing bariatric surgery., Methods: A representative sample of 665 participants aged 14 or older who underwent bariatric surgery at our center from January 1, 2010 to January 1, 2020 was included in this cohort study. MHO was defined based on specific criteria, including blood pressure, waist-to-hip ratio, and absence of diabetes., Results: Among the 665 participants, 80 individuals (12.0%) met the criteria for MHO. Female gender ( P = .021) and younger age ( P < .001) were associated with a higher likelihood of MHO. Smaller weight and BMI were observed in individuals with MHO. However, a considerable proportion of those with MHO exhibited other metabolic abnormalities, such as fatty liver (68.6%), hyperuricemia (55.3%), elevated lipid levels (58.7%), and abnormal lipoprotein levels (88%)., Conclusion: Approximately 1 in 8 individuals referred for bariatric surgery displayed the phenotype of MHO. Despite being metabolically healthy based on certain criteria, a significant proportion of individuals with MHO still exhibited metabolic abnormalities, such as fatty liver, hyperuricemia, elevated lipid levels, and abnormal lipoprotein levels, highlighting the importance of thorough metabolic evaluation in this population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19., Methods: First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects., Results: SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis., Conclusions: FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Introduction: Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB., Methods: A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m 2 ), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m 2 )., Results: Body composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB., Conclusions: PWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism., 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 © 2024 Rigamonti, Polledri, Favero, Caroli, Bondesan, Grugni, Mai, Cella, Fustinoni and Sartorio.)

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bertran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Adipose derived mesenchymal stem cells (ADMSCs) are a component of adipose tissue that in recent years has gained on importance. The progenitor cells serve as an essentially unlimited source of new adipocytes and therefore are considered to be an important determinant of the tissue's physiology. In this paper we investigated mature adipocytes differentiated from ADMSCs obtained from subcutaneous/visceral fat of patients with different metabolic status (lean, obese without and with metabolic syndrome). We focused our interests on the sphingolipid signaling pathway, i.e.a signal transduction system indispensable for cells functioning, but also implicated in the development of medical conditions associated with obesity. We observed that the cells derived from visceral tissue had significantly greater levels of almost all the examined sphingolipids (especially Cer, dhCer, SM). Moreover, obesity and metabolic syndrome present in donor patients was associated with an increased level of sphingosine kinase (SPHK) and the product of its reaction sphingosine-1-phosphate (S1P). Moreover, the condition appeared to display a tissue specific pattern. Namely, the adipocytes of subcutaneous provenance had an increased activation of ceramide de novo synthesis pathway when the donors of ADMSCs had metabolic syndrome. The above translated into greater accumulation of ceramide in the cells. To our knowledge this is the first study that demonstrated altered sphingolipid profile in the mature adipocytes differentiated from ADMSCs with respect to the stem cells tissue of origin and the donor patient metabolic status., 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 Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mitochondria dysfunction is one of the major causes of insulin resistance, and other countless complications of obesity. PGC-1α, and UCP-2 play key roles in energy expenditure regulation in the mitochondrial thermogenesis. However, the effects of bariatric surgery on the level of PGC-1α and UCP-2 and their relationships are unclear., Objective: This study aimed to investigate the effect of bariatric surgery on key pathways in energy, and to assess the potential predictive role of body composition and metabolic parameters in this regard., Settings: Hazrat-e Rasool General Hospital, Center of Excellence of International Federation for Surgery of Obesity., Methods: This prospective cohort study was carried out on 45 patients with morbid obesity who underwent Roux-en-Y gastric bypass surgery. The patients have evaluated three-time points at baseline, three, and six months after the surgery. Body composition components, the levels of PGC-1α, UCP-2, and metabolic parameters were measured three times during this study., Results: Significant changes in TWL%, EBMIL%, and metabolic lab tests were observed at three- and six months post-surgery (P < 0.001). The PGC-1α and UCP-2 had a significant increase three and then six-month post-operation compared with the baseline (P < 0.001). Moreover, multivariate linear regression analysis identified that the changing trend of PGC-1α was associated with insulin, uric Acid, HOMA-IR, fat mass and trunk fat mass. UCP-2 was associated with TSH, AST, fat mass and FFM., Conclusions: Bariatric surgery has been shown to have a positive effect on UCP-2 and PGC-1α levels, as well as body composition and metabolic parameters. As a result, it is believed that bariatric surgery could improve thermogenesis and energy expenditure by enhancing mitochondrial biogenesis and function. However, further studies are needed to fully understand the precise mechanisms and possible causal relationship., (© 2024. The Author(s).)

The human brain undergoes metabolic adaptations in obesity, but the underlying mechanisms have remained largely unknown. We compared concentrations of often reported brain metabolites measured with magnetic resonance spectroscopy ( 1 H-MRS, 3 T MRI) in the occipital lobe in subjects with obesity and lean controls under different metabolic conditions (fasting, insulin clamp, following weight loss). Brain glucose uptake (BGU) quantified with 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET)) was also performed in a subset of subjects during clamp. In dataset A, 48 participants were studied during fasting with brain 1 H-MRS, while in dataset B 21 participants underwent paired brain 1 H-MRS acquisitions under fasting and clamp conditions. In dataset C 16 subjects underwent brain 18 F-FDG-PET and 1 H-MRS during clamp. In the fasting state, total N-acetylaspartate was lower in subjects with obesity, while brain myo-inositol increased in response to hyperinsulinemia similarly in both lean participants and subjects with obesity. During clamp, BGU correlated positively with brain glutamine/glutamate, total choline, and total creatine levels. Following weight loss, brain creatine levels were increased, whereas increases in other metabolites remained not significant. To conclude, insulin signaling and glucose metabolism are significantly coupled with several of the changes in brain metabolites that occur in obesity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Resveratrol, a natural polyphenol compound contained in numerous plants, has been proposed as a treatment for obesity-related disease processes such as insulin resistance. However, in humans there are conflicting results concerning the efficacy of resveratrol in improving insulin action; the purpose of the present study was to determine whether obesity status (lean, severely obese) affects the response to resveratrol in human skeletal muscle. Primary skeletal muscle cells were derived from biopsies obtained from age-matched lean and insulin-resistant women with severe obesity and incubated with resveratrol (1 µM) for 24 h. Insulin-stimulated glucose oxidation and incorporation into glycogen, insulin signal transduction, and energy-sensitive protein targets [AMP-activated protein kinase (AMPK), Sirt1, and PGC1α] were analyzed. Insulin-stimulated glycogen synthesis, glucose oxidation, and AMPK phosphorylation increased with resveratrol incubation compared with the nonresveratrol conditions (main treatment effect for resveratrol). Resveratrol further increased IRS1, Akt, and TBC1D4 insulin-stimulated phosphorylation and SIRT1 content in myotubes from lean women, but not in women with severe obesity. Resveratrol improves insulin action in primary human skeletal myotubes derived from lean women and women with severe obesity. In women with obesity, these improvements may be associated with enhanced AMPK phosphorylation with resveratrol treatment. NEW & NOTEWORTHY A physiologically relevant dose of resveratrol increases insulin-stimulated glucose oxidation and glycogen synthesis in myotubes from individuals with severe obesity. Furthermore, resveratrol improved insulin signal transduction in myotubes from lean individuals but not from individuals with obesity. Activation of AMPK plays a role in resveratrol-induced improvements in glucose metabolism in individuals with severe obesity.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents., Aim: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD., Methods: This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study. Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD. Plasma samples were collected during surgery for miRNA profiling. A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform. We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age, sex, race, and other key covariates. Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD., Results: We identified 16 upregulated plasma miRNAs, including miR-193a-5p and miR-193b-5p, and 22 downregulated plasma miRNAs, including miR-1282 and miR-6734-5p, in adolescents with NAFLD. Moreover, 52, 16, 15, and 9 plasma miRNAs were associated with NASH, fibrosis, ballooning degeneration, and lobular inflammation, respectively. Collectively, 16 miRNAs were associated with two or more histological features of NAFLD. Among those miRNAs, miR-411-5p was downregulated in NASH, ballooning, and fibrosis, while miR-122-5p, miR-1343-5p, miR-193a-5p, miR-193b-5p, and miR-7845-5p were consistently and positively associated with all histological features of NAFLD. Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression, while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B., Conclusion: Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity. Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Obesity rates in the U.S. continue to increase, with nearly 50% of the population being either obese or morbidly obese. Obesity, along with female sex, are leading risk factors for sporadic Alzheimer's Disease (AD) necessitating the need to better understand how these variables impact cellular function independent of age or genetic mutations. Animal and clinical studies both indicate that autophagy-lysosomal pathway (ALP) dysfunction is among the earliest known cellular systems to become perturbed in AD, preceding cognitive decline, yet little is known about how obesity and sex affects these cellular functions in the hippocampus, a brain region uniquely susceptible to the negative effects of obesity. We hypothesized that obesity would negatively affect key markers of ALP in the hippocampus, effects would vary based on sex, and that caloric restriction would counteract obesity effects., Methods: Female and male mice were placed on an obesogenic diet for 10 months, at which point half were switched to caloric restriction for three months, followed by cognitive testing in the Morris watermaze. Hippocampus was analyzed by western blot and qPCR., Results: Cognitive function in female mice responded differently to caloric restriction based on whether they were on a normal or obesogenic diet; male cognition was only mildly affected by caloric restriction and not obesity. Significant male-specific changes occurred in cellular markers of autophagy, including obesity increasing pAkt, Slc38a9, and Atg12, while caloric restriction reduced pRPS6 and increased Atg7. In contrast females experienced changes due to diet/caloric restriction predominately in lysosomal markers including increased TFE3, FLCN, FNIP2, and pAMPK., Conclusions: Results support that hippocampal ALP is a target of obesity and that sex shapes molecular responses, while providing insight into how dietary manipulations affect learning and memory based on sex., (© 2023. The Author(s).)

Introduction: Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be split into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and post-prandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or SG as the first step of SADI-S., Methods: Subjects submitted to SADI-S (n = 7) or SG (n = 7) at a tertiary referral public academic hospital underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively., Results: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate, and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up., Conclusions: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. These data provide support for surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Cardio-ankle vascular index (CAVI) is an arterial stiffness index that correlates inversely with body mass index (BMI) and subcutaneous fat area. Lipoprotein lipase (LPL) that catalyzes the hydrolysis of serum triglycerides is produced mainly in adipocytes. Serum LPL mass reflects LPL expression in adipose tissue, and its changes correlate inversely with changes in CAVI. We hypothesized that LPL derived from subcutaneous adipose tissue (SAT) suppresses the progression of arteriosclerosis and examined the relationship of LPL gene expression in different adipose tissues and serum LPL mass with CAVI in Japanese patients with severe obesity undergoing laparoscopic sleeve gastrectomy (LSG)., Methods: This study was a single-center retrospective database analysis. Fifty Japanese patients who underwent LSG and had 1-year postoperative follow-up data were enrolled (mean age 47.5 years, baseline BMI 46.6 kg/m2, baseline HbA1c 6.7%). SAT and visceral adipose tissue (VAT) samples were obtained during LSG surgery. LPL gene expression was analyzed by real-time PCR. Serum LPL mass was measured by ELISA using a specific monoclonal antibody against LPL., Results: At baseline, LPL mRNA expression in SAT correlated positively with serum LPL mass, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT was correlated, and serum LPL mass tended to correlate inversely with the number of metabolic syndrome symptoms, but LPL mRNA expression in VAT did not. LPL mRNA expression in SAT and CAVI tended to correlate inversely in the group with visceral-to-subcutaneous fat ratio of 0.4 or higher, which is considered metabolically severe. Serum LPL mass increased 1 year after LSG. Change in serum LPL mass at 1 year after LSG tended to be an independent factor inversely associated with change in CAVI., Conclusions: Serum LPL mass reflected LPL mRNA expression in SAT in Japanese patients with severe obesity, and LPL mRNA expression in SAT was associated with CAVI in patients with visceral obesity. The change in serum LPL mass after LSG tended to independently contribute inversely to the change in CAVI. This study suggests that LPL derived from SAT may suppress the progression of arteriosclerosis., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Obesity is an enormous health problem, and many patients do not respond to any of the available therapies. Deep brain stimulation (DBS) is currently investigated as a potential treatment for morbid obesity. In this study, we tested the hypothesis that high-frequency DBS targeting the nucleus accumbens (NAc) shell region reduces food intake and weight gain in mice fed a high-fat diet. We implanted male C57BL/6J mice with bilateral electrodes and a head-mounted microstimulator enabling continuous stimulation for up to 5 weeks. In successfully operated animals (n = 9 per group, high-frequency vs. sham stimulation), we investigated immediate and long-term stimulation effects on metabolic and behavioral phenotypes. Here we show that stimulation acutely induced a transient reduction in energy expenditure and locomotor activity but did not significantly affect spontaneous food intake, social interaction, anxiety or exploratory behaviors. In contrast, continuous stimulation over 5 weeks led to a decrease in food intake and thigmotaxis (the tendency to stay near walls in an open lit arena). However, chronic stimulation did not substantially change weight gain in mice fed a high-fat diet. Our results do not support the use of continuous high-frequency NAc shell DBS as a treatment for obesity. However, DBS can alter obesity-related parameters with differing short and long-term effects. Therefore, future research should employ time and context-sensitive experimental designs to assess the potential of DBS for clinical translation in this area., (© 2023. The Author(s).)

In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies. NEW & NOTEWORTHY This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.

The severity of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and it is not yet clearly understood which patients will progress to liver fibrosis or cirrhosis. SPARC (Secreted Protein Acidic and Rich in Cysteine) has been involved in NAFLD pathogenesis in mice and humans. The aim of this study was to investigate the role of SPARC in inflammasome activation, and to evaluate the relationship between the hepatic expression of inflammasome genes and the biochemical and histological characteristics of NAFLD in obese patients. In vitro studies were conducted in a macrophage cell line and primary hepatocyte cultures to assess the effect of SPARC on inflammasome. A NAFLD model was established in SPARC knockout (SPARC -/- ) and SPARC +/+ mice to explore inflammasome activation. A hepatic RNAseq database from NAFLD patients was analyzed to identify genes associated with SPARC expression. The results were validated in a prospective cohort of 59 morbidly obese patients with NAFLD undergoing bariatric surgery. Our results reveal that SPARC alone or in combination with saturated fatty acids promoted IL-1β expression in cell cultures. SPARC -/- mice had reduced hepatic inflammasome activation during the progression of NAFLD. NAFLD patients showed increased expression of SPARC , NLRP3 , CASP1 , and IL-1 β. Gene ontology analysis revealed that genes positively correlated with SPARC are linked to inflammasome-related pathways during the progression of the disease, enabling the differentiation of patients between steatosis and steatohepatitis. In conclusion, SPARC may play a role in hepatic inflammasome activation in NAFLD.

Background/objectives: Obesity-associated metabolic dysfunction and inflammation can be ameliorated by bariatric surgery. While obesity is also linked to impaired B cell activation, differentiation, and persistence in response to infection and vaccination little is known about post-operative immune B cell compartment and to what extent dysregulation in B cell pathways can be reversed. To bridge this gap in knowledge, we carried out in-depth evaluation of B cell composition in individuals with obesity prior to and following bariatric surgery compared to lean controls., Subjects/methods: We recruited individuals with obesity (BMI at least 35 kg/m 2 ) before bariatric surgery (n = 21) and followed them up 6 months post-operatively (n = 17). As controls we recruited age- and sex-matched lean (BMI < 25) individuals (n = 18). We carried out comprehensive immunophenotyping of peripheral blood B cells as well as interrogated their association with inflammatory and metabolic parameters., Results: In obesity the balance of antigen-inexperienced and memory B cells in the peripheral blood is altered, with an expansion of naïve and a reduction in total memory B cells. 6 months following bariatric surgery this balance is restored. However, post-operative patients are uniquely characterised by an increase in B cell subsets associated with chronic inflammation - CD11c + CXCR5 - IgD - CD27 - double negative 2 (DN2) B cells and CD27 + CD38 ++ plasmablasts. Correlations between B cells subsets, inflammatory and metabolic parameters were distinct in lean people and individuals with obesity pre- and post-bariatric surgery., Conclusions: Bariatric surgery patients display a unique B cell profile 6 months post-operatively; this bears minimal resemblance to that of pre-operative patients and only partially overlaps with that of lean controls. Post-operative differences in the B cell compartment compared to lean controls are detected despite global amelioration of inflammation and restoration of metabolic health. Collectively, this indicates that bariatric surgery creates a specific immunometabolic state with potential implications for health outcomes., (© 2023. The Author(s).)

Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very popular and widely used. LSG leads to weight loss and metabolic improvement and also changes adipokine levels, although it is just a restrictive operation. We describe changes in pro-inflammatory (leptin, resistin, visfatin and chemerin) and anti-inflammatory adipokines (adiponectin, omentin), with adiponectin and leptin being most studied. Their levels are markedly changed after LSG and this may partially explain the weight loss seen after LSG. Adipokines are closely connected to insulin resistance and chronic inflammation both being positively influenced after LSG. Leptin regulates amount of body fat, appetite, thermogenesis and metabolic rate and its levels are positively correlated with both weight and BMI changes after operation. Resistin influences insulin sensitivity, modulates body cholesterol trafficking and its changes after operation correlate with BMI, waist circumference, fat mass, LDL cholesterol and C-reactive protein. Chemerin, an important component of immune system, decreases after bariatric surgery and its levels correlate with BMI, triglyceride levels, and blood glucose. On the other hand, pro-inflammatory adipokine adiponectin, which influences fatty acid oxidation, browning of fat tissue and energy metabolism, is declining after LSG. This decline explains improvement of glucose status after bariatric surgery in patients with diabetes and is correlated with BMI loss, waist circumference and LDL cholesterol level. Effect of LSG goes beyond calory restriction and the changes of adipokines have a great impact on health status of the bariatric patients.

Background: Obesity, a public health problem, is a state of metainflammation that influences the development of chronic degenerative diseases, particularly in patients with severe obesity., Objective: The objective of this study was to evidence immunometabolic differences in patients with different degrees of obesity, including severe obesity, by determining correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables., Methods: Peripheral blood immune cells (CD4+, CD8+ memory and effector T lymphocytes) were analyzed, and measures of body composition, blood pressure, and biochemical composition (glucose, glycated hemoglobin (HbA1c), insulin, C-reactive protein (CRP), and the lipid profile) were carried out in patients with different degrees of obesity., Results: The patients were classified according to total body fat (TBF) percentage as normal body fat, class 1 and 2 obesity, class 3 obesity, and class 4 obesity. The greater the TBF percentage, the more pronounced the differences in body composition (such as a decrease in the fat-free mass (FFM) that is defined as sarcopenic obesity) and the immunometabolic profile. There was an increase of CD3+ T lymphocytes (mainly CD4+, CD4+CD62-, and CD8+CD45RO+ T lymphocytes) and an increase in the TBF percentage (severity of obesity)., Conclusions: The correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables demonstrated the existence of a chronic, low-intensity inflammatory process in obesity. Therefore, measuring the immunometabolic profile by means of lymphocyte subpopulations in patients with severe obesity could be useful to determine the severity of the disease and the increased risk of presenting obesity-associated chronic degenerative diseases., Competing Interests: The authors declare there are no competing interests., (©2023 Rivera-Carranza et al.)

The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [ 11 C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum ( p = 0.032), posterior putamen ( p = 0.012), and anterior caudate ( p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.

This study investigated the importance of a metabolomic analysis in a complex disease such as nonalcoholic steatohepatitis (NASH) associated with obesity. Using an untargeted metabolomics technique, we studied blood metabolites in 216 morbidly obese women with liver histological diagnosis. A total of 172 patients were diagnosed with nonalcoholic fatty liver disease (NAFLD), and 44 were diagnosed with normal liver (NL). Patients with NAFLD were classified into simple steatosis ( n = 66) and NASH ( n = 106) categories. A comparative analysis of metabolites levels between NASH and NL demonstrated significant differences in lipid metabolites and derivatives, mainly from the phospholipid group. In NASH, there were increased levels of several phosphatidylinositols and phosphatidylethanolamines, as well as isolated metabolites such as diacylglycerol 34:1, lyso-phosphatidylethanolamine 20:3 and sphingomyelin 38:1. By contrast, there were decreased levels of acylcarnitines, sphingomyelins and linoleic acid. These findings may facilitate identification studies of the main pathogenic metabolic pathways related to NASH and may also have a possible applicability in a panel of metabolites to be used as biomarkers in future algorithms of the disease diagnosis and its follow-up. Further confirmatory studies in groups with different ages and sexes are necessary.

Introduction: Metabolic surgery is a more effective manner to manage weight loss for morbidly obese patients than conservative therapy. There are many surgical and endoscopic modalities to choose which represents a real challenge for bariatric surgeons. LGCP is a restrictive procedure, the greater curvature of stomach is folded into the gastric lumen in one or two layers. Endoscopic bariatric and metabolic therapies (EBMTs) are evolving methods in metabolic interventions' inventory. There are two methods imitating LGCP (endoscopic sleeve gastroplasty and primary obesity surgery endoluminal)., Evidence Acquisition: We have conducted wide literature searches in Pubmed database in order to perform meta-analysis comparing endoscopic and surgical treatment modalities (EBMTs vs. LGCP). Safety and weight-loss outcomes were measured., Evidence Synthesis: A number of 3585 patients for EBMTs and 2350 cases for LGCP were enrolled to final analysis. Comparison of complications (Clavien Dindo grade 1-5) showed almost equal risk. Percent of excess of weight loss was well matched at all follow-up timepoints, however, percent of total weight loss was in favor of LGCP. Changes of BMI were compared and showed similar efficacy for both methods., Conclusions: EBMTs appeared to be superior to LGCP regarding safety but differences did not reach statistical threshold. Weight loss outcomes were favorable after each method. EBMTs imitating LGCP are promising safe and effective methods.

In Brief: The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes., Abstract: Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

De novo lipogenesis (DNL) in visceral adipose tissue (VAT) is associated with systemic insulin sensitivity. DNL in VAT is regulated through ChREBP activity and glucose uptake through Glut4 (encoded by Slc2a4 ). Slc2a4 expression, ChREBP activity, and DNL are decreased in obesity, the underlying cause however remains unidentified. We hypothesize that increased DNA methylation in an enhancer region of Slc2a4 decreases Slc2a4 expression in obesity and insulin resistance. We found that SLC2A4 expression in VAT of morbidly obese subjects with high HbA1c (>6.5%, n = 35) is decreased, whereas DNA methylation is concomitantly increased compared to morbidly obese subjects with low HbA1c (≤6.5%, n = 65). In diet-induced obese (DIO) mice, DNA methylation of Slc2a4 persistently increases with the onset of obesity and insulin resistance, while gene expression progressively decreases. The regulatory impact of DNA methylation in the investigated enhancer region on SLC2A4 gene expression was validated with a reporter gene assay. Additionally, treatment of 3T3 pre-adipocytes with palmitate/oleate during differentiation decreased DNA methylation and increased Slc2a4 expression. These findings highlight a potential regulation of Slc2a4 by DNA methylation in VAT, which is induced by fatty acids and may play a role in the progression of obesity and insulin resistance in humans.

This study's objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue-liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT-qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.

Aim: The Diabetes risk index (DRI) is a composite of NMR-measured lipoproteins and branched chain amino acids predictive of diabetes mellitus development. Bariatric surgery is indicated in patients with severe obesity, many of whom are at high-risk for developing diabetes. Substantial weight loss occurs following bariatric surgery and sustained weight loss likely contributes to reductions in the development of diabetes and cardiovascular disease. However, some evidence suggests that bariatric surgical procedures themselves may contribute to reducing risk of these conditions independent of weight loss. We aimed to investigate DRI and its association with reductions in body weight and adiposity over one year following bariatric surgery., Methods: We examined 51 severely obese premenopausal women without diabetes. DRI, BMI, body weight and waist measurements were made before and at 1, 6 and 12 months after Roux-en-Y Gastric Bypass (RYGB) or Sleeve Gastrectomy. Values were compared to healthy women with normal BMI (18.5-24.9 kg/m 2 ; n = 15)., Results: Non-diabetic women with severe obesity (BMI 44.7 ± 6.2 kg/m 2 ) exhibited significantly elevated DRI scores prior to surgery versus controls (35 [26, 39] vs 12 [1, 20]; p < 0.0001). At 1 month after surgery, BMI decreased 5.1 ± 1.1 kg/m 2 , but DRI decreased so that it no longer differed from that of normal BMI controls (1.9 [1, 17] vs control 12 [1, 20]; p = 0.35). Subjects continued to lose weight, whereas DRI remained similar, throughout follow-up with DRI 1.0 [1, 7] at 12 months. Changes in DRI did not correlate with changes in BMI, body weight or waist circumference at any time during follow-up. There was no difference in change in DRI between surgical procedures or pre-operative metabolic syndrome status., Conclusions: Our analysis of DRI scores supports the capacity of bariatric surgery to reduce risk of developing diabetes in severely obese individuals. Our findings suggest that bariatric surgical techniques may have inherent effects that improve cardiometabolic risk independent of reductions in body weight or adiposity., (© 2022. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved., Scope of Review: The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents., Major Conclusions: Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Obesity is an ever-increasing phenomenon, with 42% of Americans being considered obese (BMI ≥ 30) and 9.2% being considered morbidly obese (BMI ≥ 40) as of 2016. With obesity being characterized by an abundance of adipose tissue expansion, abnormal tissue remodeling is a typical consequence. Importantly, this pathological tissue expansion is associated with many alterations in the cellular populations and phenotypes within the tissue, lending to cellular, paracrine, mechanical, and metabolic alterations that have local and systemic effects, including diabetes and cardiovascular disease. In particular, vascular dynamics shift during the progression of obesity, providing signaling cues that drive metabolic dysfunction. In this review, paracrine-, autocrine-, and matrix-dependent signaling between adipocytes and endothelial cells is discussed in the context of the development and progression of obesity and its consequential diseases, including adipose fibrosis, diabetes, and cardiovascular disease.

Although bariatric surgery is known to change the metabolome, it is unclear if this is specific for the intervention or a consequence of the induced bodyweight loss. As the weight loss after Roux-en-Y Gastric Bypass (RYGB) can hardly be mimicked with an evenly effective diet in humans , translational research efforts might be helpful. A group of 188 plasma metabolites of 46 patients from the randomized controlled Würzburg Adipositas Study (WAS) and from RYGB-treated rats ( n = 6) as well as body-weight-matched controls ( n = 7) were measured using liquid chromatography tandem mass spectrometry. WAS participants were randomized into intensive lifestyle modification (LS, n = 24) or RYGB (OP, n = 22). In patients in the WAS cohort, only bariatric surgery achieved a sustained weight loss (BMI -34.3% (OP) vs. -1.2% (LS), p ≤ 0.01). An explicit shift in the metabolomic profile was found in 57 metabolites in the human cohort and in 62 metabolites in the rodent model. Significantly higher levels of sphingolipids and lecithins were detected in both surgical groups but not in the conservatively treated human and animal groups. RYGB leads to a characteristic metabolomic profile, which differs distinctly from that following non-surgical intervention. Analysis of the human and rat data revealed that RYGB induces specific changes in the metabolome independent of weight loss.

Context: Laparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized., Objective: We determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake., Design, Setting, Participants: Prospective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG., Main Outcomes: FCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography., Results: Mean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01)., Conclusions: FCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG., (Published by Oxford University Press on behalf of the Endocrine Society 2022.)

Obesity prevalence is rising globally, as are the number of chronic disorders connected with obesity, such as diabetes, non-alcoholic fatty liver disease, dyslipidemia, and hypertension. Bariatric surgery is also becoming more common, and it remains the most effective and long-term treatment for obesity. This study will assess the influence of Laparoscopic Sleeve Gastrectomy (LSG) on gut microbiota in people with obesity before and after surgery. The findings shed new light on the changes in gut microbiota in Saudi people with obesity following LSG. In conclusion, LSG may improve the metabolic profile, resulting in decreased fat mass and increased lean mass, as well as improving the microbial composition balance in the gastrointestinal tract, but this is still not equivalent to normal weight microbiology. A range of factors, including patient characteristics, geographic dispersion, type of operation, technique, and nutritional and caloric restriction, could explain differences in abundance between studies. This information could point to a novel and, most likely, tailored strategy in obesity therapy, which could eventually be incorporated into health evaluations and monitoring in preventive health care or clinical medicine.

Introduction: High soluble (pro)renin receptor (s[P]RR) level in circulation is reported in obese patients; however, it is unclear which body composition components are responsible for it. In this study, the authors examined blood s(P)RR levels and ATP6AP2 gene expression levels in visceral and subcutaneous adipose tissue (VAT, SAT) in severely obese patients who underwent laparoscopic sleeve gastrectomy (LSG), with the aim of clarifying the relationship with body composition and metabolic factors., Methods: Seventy five cases who underwent LSG between 2011 and 2015 and were postoperatively followed-up for 12 months at the Toho University Sakura Medical Center were included in the analysis of the cross-sectional survey at baseline, and 33 cases were included in the analysis of the longitudinal survey during the 12 months after LSG. We evaluated body composition, glycolipid parameters, liver/renal function, as well as serum s(P)RR level and ATP6AP2 mRNA expression level in VAT and SAT., Results: The mean serum s(P)RR level at baseline was 26.1 ng/mL, this value was considered higher than values in healthy subjects. There was no significant difference in the expression level of ATP6AP2 mRNA between VAT and SAT. At baseline, multiple regression analysis for the association between s(P)RR and variables identified that visceral fat area, HOMA2-IR, and UACR showed the independent relationships with s(P)RR. During the 12 months after LSG, body weight, serum s(P)RR level showed a significant decrease (from 30.0 ± 7.0 to 21.9 ± 4.3). Multiple regression analysis for the association between the change in s(P)RR and variables showed that changes in visceral fat area, and alanine transaminase were independently related to the change in s(P)RR., Conclusion: This study showed that blood s(P)RR level was high in severely obese patients, decreased with weight loss by LSG, and was associated with visceral fat area in both pre- and postoperative changes. The results suggest that blood s(P)RR levels in obese patients may reflect the involvement of visceral adipose (P)RR in insulin resistance and renal damage mechanisms associated with obesity., (© 2023 The Author(s). Published by S. Karger AG, Basel.)