Search

Cancer ranks among the five leading causes of death in almost all countries and has important repercussions for individual and public health, the healthcare system and society in general. Obesity increases the incidence of many types of cancer, but growing evidence suggests that physical activity may decrease risk for developing a variety of obesity-related cancer types, and in some cases also, improve cancer prognosis and mortality rates. This review summarizes recent evidence on the effect of physical activity on obesity-related cancer prevention and survival. For some cancers, including breast, colorectal, and endometrial cancer, there is strong evidence for a preventative effect of exercise, but for many others, including gallbladder and kidney cancer, and multiple myeloma, evidence is inconsistent or largely lacking. Though many potential mechanisms have been proposed to explain the onco-protective effect of exercise, including improved insulin sensitivity, alterations in sex hormone availability, improved immune function and inflammation, myokine secretion, and modulation of intracellular signaling at the level of AMP kinase, the exact mechanism(s) of action within each cancer subtype remains poorly defined. Overall, a deeper understanding of how exercise can help against cancer and of the exercise parameters that can be tweaked to optimize exercise prescription is necessary and should be the subject of future investigation.

Prenatal nonessential metals may contribute to postnatal adiposity, whereas essential metals may have metabolic benefits. We evaluated joint and individual associations between prenatal metals and childhood adiposity.We measured concentrations of six nonessential (arsenic, barium, cadmium, cesium, lead, and mercury) and four essential (magnesium, manganese, selenium, and zinc) metals in first trimester maternal blood from a prebirth cohort. We collected anthropometric measures in early childhood, mid-childhood, and early adolescence including subscapular+tricep skinfold thickness (mm) (N = 715-859), waist circumference (cm) (N = 717-882), and body mass index (BMI) (z-score) (N = 716-875). We measured adiposity in mid-childhood and early adolescence using bone densitometry total- and trunk- fat mass index (kg/m 2 ) (N = 511-599). We estimated associations using adjusted quantile g-computation and linear regression.The nonessential metal mixture was associated with higher total (β = 0.07, 95% CI = 0.01, 0.12) and trunk fat mass index (β = 0.12, CI = 0.02, 0.22), waist circumference (β = 0.01, CI = 0.00, 0.01), and BMI (β = 0.24, CI = 0.07, 0.41) in mid-childhood, and total fat mass index (β = 0.07, CI = 0.01, 0.14), and BMI (β = 0.19, CI = 0.02, 0.37) in early adolescence. The essential metal mixture was associated with lower early adolescence total-(β = -0.11, CI = -0.17, -0.04) and trunk- fat mass index (β = -0.13, CI = -0.21, -0.05), subscapular+tricep skinfold thickness (β = -0.02, CI = -0.03, -0.00), waist circumference (β = -0.003, CI = -0.01, -0.00), and BMI (β = -0.16, CI = -0.28, -0.04). Cadmium and cesium were individually associated with childhood adiposity at different timepoints.Prenatal first-trimester essential metals were associated with lower childhood adiposity, whereas nonessential metals were associated with higher adiposity into adolescence.

We studied healthy infant feeding practices among 308 mother-infant pairs, including exclusive breastmilk, satiety cues, complementary food introduction, sugary beverage intake, and bottle use in bed. We examined associations of individual and cumulative infant feeding practices through 12 months of age with body mass index (BMI) z -score at 2 years. Exclusive breastmilk and avoidance of bottle use in bed were associated with lower BMI z -score (β -0.29 units; 95% CI, -0.56, -0.02 units and β -0.32 units; 95% CI, -0.57, -0.07, respectively), when accounting for maternal pre-pregnancy BMI, household income, infant sex, race, and ethnicity. Adherence to 4--5 practices, compared to ≤ 2 practices, was associated with lower BMI z -score (β -0.84 units; 95% CI, -1.35, -0.34 units). Adherence to healthy infant feeding practices may reduce risk of excessive adiposity in early childhood. Targeting multiple infant feeding practices may be a more effective way to prevent childhood adiposity.

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3–7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8–10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10–14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.

In human studies, new model systems are needed for improved mechanistic investigation of developmental predisposition for metabolic disease but also to serve as benchmarks in early life prevention or intervention efforts. In this regard, human infant umbilical cord-derived mesenchymal stem cells (MSCs) are an emerging tool. However, long-term clinical relevance to in vivo markers of metabolic disease is unknown.In a cohort of 124 mother/child dyads, this study tested the hypothesis that triglyceride content (TG) of infant MSCs undergoing adipogenesis in vitro (MSC-TG) is associated with in vivo adiposity (percent fat mass) from birth to early childhood and with fasting glucose and insulin in early childhood.MSC-TG was positively associated with in vivo child adiposity at birth, age 4 to 6 months, and age 4 to 6 years. MSC-TG was associated with fasting glucose, but not insulin, at 4 to 6 years. Importantly, MSC-TG explained an additional 13% variance in child adiposity at 4 to 6 years, after accounting for other established birth predictors (weight and percent fat mass at birth) and other established covariates related to child adiposity (e.g., breastfeeding exposure, physical activity).This work demonstrates the strength of the MSC model for predicting offspring metabolic phenotype into childhood, even when considering the important contribution of other early life risk factors.

Growing evidence has linked gut microbiota with regulation of adiposity. We aimed to examine whether the genetically determined relative abundance of gut microbial taxa was associated with long-term changes in adiposity and body composition among individuals who were overweight or obese in weight-loss diet interventions.The study included 692 participants with overweight or obese from the POUNDS Lost trial. We created a genetic risk score (GRS) for the relevant abundance of gut microbial taxa using 20 single nucleotide polymorphisms identified from a recent genome-wide association study. Body composition was assessed using dual-energy X-ray absorptiometry.Higher GRS for the relative abundance of gut microbial taxa was significantly associated with greater reductions in waist circumference, total fat mass (FM), whole-body total percentage of fat mass (FM%), and percentage of trunk fat (TF%) at 2 years (p = 0.022, 0.034, 0.023, 0.023, respectively). In addition, dietary protein significantly modified the association between GRS for gut microbial abundance and changes in total FM, FM%, and TF% (p-interactions = 0.04, 0.013, and 0.006, respectively) at 6-month, when the maximum weight loss was achieved, even though such interactions were attenuated at 2 years. In the average-protein diet group, a higher microbial abundance GRS was associated with greater reductions in total FM (p = 0.007), FM% (p = 0.002), and TF% (p 0.001) at 6 months, while no associations were found in the high-protein diet group (p 0.05).Our results suggest that the higher genetically determined relative abundance of gut microbial taxa may be related to long-term improvement of whole-body and central fatness and body composition in response to low-calorie diet interventions.

Many studies have investigated the effects of soy isoflavones on weight control, but few have focused on the role of equol, a gut-derived metabolite of daidzein with greater bioavailability than other soy isoflavones.This study examined the association of equol production with obesity and explored the mediating roles of equol-related gut microbiota and microbial carnitine metabolites.This 6.6-y prospective study included 2958 Chinese adults (2011 females and 947 males) aged 60.6 ± 6.0 y (mean ± SD) at baseline. Urinary equol and isoflavones were measured using HPLC-tandem MS. BMI, percentage fat mass (%FM), and serum triglycerides (TGs) were assessed every 3 y. Metagenomics sequencing and assessment of carnitine metabolites in feces were performed in a subsample of 897 participants.Urinary equol, but not daidzein and genistein, was independently and inversely associated with the obesity-related indicators of BMI, %FM, and a biomarker (TGs). Equol producers (EPs) had lower odds of adiposity conditions and a reduced risk of 6.6-y obesity progression than non-EPs among total participants. Gut microbial analyses indicated that EPs had higher microbiome species richness (P = 3.42 × 10-5) and significantly different β-diversity of gut microbiota compared with the non-EP group (P = 0.001), with 20 of 162 species differing significantly. EPs (compared with non-EPs) had higher abundances of Alistipes senegalensis and Coprococcus catus but lower abundances of Ruminococcus gnavus (false discovery rate 0.05). Among the 7 determined fecal acylcarnitine metabolites, palmitoylcarnitine, oleylcarnitine 18:1, and stearylcarnitine were inversely associated with EPs but positively correlated with obesity conditions and progression. Path analyses indicated that the beneficial association between equol and obesity might be mediated by gut microbiota and decreased production of 3 acylcarnitines in feces.This study suggests a beneficial association between equol and obesity, mediated by the gut microbiome and acylcarnitines, in adults.This trial was registered at clinicaltrials.gov as NCT03179657.

To evaluate the associations between liver fat content and cardiometabolic parameters to explore potential threshold values that define metabolically healthy liver fat content, and to examine the association of liver fat content with cardiovascular events as well as its longitudinal progression.Participants in the Dallas Heart Study underwent clinical evaluation, including laboratory testing, and liver fat quantification by magnetic resonance spectroscopy (MRS) at baseline (N = 2287) and at follow-up (N = 343) after a mean of 7.3 years. Cardiovascular events were adjudicated (12 years).The mean age at study entry was 44 years, 47% of participants were men, and 48% were African American. The following cardiometabolic biomarkers worsened across liver fat quintiles (P 0.0001): body mass index (BMI); waist circumference; prevalence of hypertension; prevalence of diabetes; cholesterol, triglyceride, high-sensitivity C-reactive protein (CRP), leptin and fasting glucose levels; homeostatic model assessment of insulin resistance index (HOMA-IR); coronary artery calcium score; visceral adipose tissue; abdominal subcutaneous adipose tissue; and lower body subcutaneous adipose tissue. Cardiovascular events were comparable across groups defined by tertile of baseline liver fat content. Change in BMI (R = 0.40), waist circumference (R = 0.35), CRP (R = 0.31), alanine aminotransferase (R = 0.27), HOMA-IR (R = 0.26), aspartate transaminase (R = 0.15) and triglycerides (R = 0.12) significantly correlated with change in liver fat content (P 0.01 for all).Clinically relevant metabolic abnormalities were higher across quintiles of liver fat, with increases noted well within normal liver fat ranges, but cardiovascular events were not associated with liver fat content. Longitudinal changes in metabolic parameters, especially adiposity-related parameters, were correlated with change in liver fat content.

Monoacylglycerol O-acyltransferase 1 (Mogat1), a lipogenic enzyme that converts monoacylglycerol to diacylglycerol, is highly expressed in adipocytes and may regulate lipolysis by re-esterifying fatty acids released during times when lipolytic rates are low. However, the role of Mogat1 in regulating adipocyte fat storage during differentiation and diet-induced obesity is relatively understudied.Here, adipocyte-specific Mogat1 knockout mice were generated and subjected to a high-fat diet to determine the effects of Mogat1 deficiency on diet-induced obesity. Mogat1 floxed mice were also used to develop preadipocyte cell lines wherein Mogat1 could be conditionally knocked out to study adipocyte differentiation in vitro.In preadipocytes, it was found that Mogat1 knockout at the onset of preadipocyte differentiation prevented the accumulation of glycerolipids and reduced the differentiation capacity of preadipocytes. However, the loss of adipocyte Mogat1 did not affect weight gain or fat mass induced by a high-fat diet in mice. Furthermore, loss of Mogat1 in adipocytes did not affect plasma lipid or glucose concentrations or insulin tolerance.These data suggest Mogat1 may play a role in adipocyte differentiation in vitro but not adipose tissue expansion in response to nutrient overload in mice.

Aims/hypothesis Excess adiposity is differentially associated with increased risk of cardiometabolic disease in men and women, according to observational studies. Causal inference studies largely assume a linear relationship between BMI and cardiometabolic outcomes, which may not be the case. In this study, we investigated the shapes of the causal relationships between BMI and cardiometabolic diseases and risk factors. We further investigated sex differences within the causal framework. Methods To assess causal relationships between BMI and the outcomes, we used two-stage least-squares Mendelian randomisation (MR), with a polygenic risk score for BMI as the instrumental variable. To elucidate the shapes of the causal relationships, we used a non-linear MR fractional polynomial method, and used piecewise MR to investigate threshold relationships and confirm the shapes. Results BMI was associated with type 2 diabetes (OR 3.10; 95% CI 2.73, 3.53), hypertension (OR 1.53; 95% CI 1.44, 1.62) and coronary artery disease (OR 1.20; 95% CI 1.08, 1.33), but not chronic kidney disease (OR 1.08; 95% CI 0.67, 1.72) or stroke (OR 1.08; 95% CI 0.92, 1.28). The data suggest that these relationships are non-linear. For cardiometabolic risk factors, BMI was positively associated with glucose, HbA1c, triacylglycerol levels and both systolic and diastolic BP. BMI had an inverse causal relationship with total cholesterol, LDL-cholesterol and HDL-cholesterol. The data suggest a non-linear causal relationship between BMI and BP and other biomarkers (pp Conclusions/interpretation We describe the shapes of causal effects of BMI on cardiometabolic diseases and risk factors, and report sex differences in the causal effects of BMI on LDL-cholesterol. We found evidence of non-linearity in the causal effect of BMI on diseases and risk factor biomarkers. Reducing excess adiposity is highly beneficial for health, but there is greater need to consider biological sex in the management of adiposity. Graphical abstract

It has been proposed that direct measurement of adiposity has a greater accuracy as a prognostic factor in various malignancies than anthropometric measures such as BMI. We evaluated the association of visceral and subcutaneous adiposity with outcomes in patients with hematological malignancies with a systematic review and meta-analysis. This systematic review included patients with hematological malignancies who had the analysis of overall mortality and progression-free survival according to their adiposity status. We identified 3137 articles, of which we included seven studies. Patients with visceral low visceral adiposity had 2 times greater mortality risk (HR 2.02, P = .0004) and 80% higher risk of death or disease progression (HR 2.98, P = 0.0002), than patients with normal visceral obesity. Patients classified with subcutaneous adipopenia had almost 3 times greater mortality risk. In conclusion, hematological malignancy patients having low adiposity (subcutaneous or visceral) have worse outcomes.

Background: Obesity classifications vary globally and the impact of older age adiposity on incident diabetes has not been well-studied.Methods: We examined a random sample of 2,809 participants aged ≥60 years in China, who were free of diabetes at baseline and were followed up for up to 10 years to document diabetes (n=178). The incidence of diabetes was assessed in relation to different cut-off points of body mass index (BMI) and waist circumference (WC) in multiple adjusted Cox regression models.Results: The diabetic risk in the cohort increased linearly with the continuous and quartile variables of BMI and WC. The BMI-World Health Organization (WHO) and BMI-China criteria analysis did not show such a linear relationship, however, the BMI-Asian/Hong Kong criteria did; adjusted hazards ratio (HR) was 0.42 (95% confidence interval [CI], 0.20 to 0.90) in BMI 2, 1.46 (95% CI, 0.99 to 2.14) in 23–≤26 kg/m2, and 1.63 (95% CI, 1.09 to 2.45) in ≥26 kg/m2. The WC-China criteria revealed a slightly better prediction of diabetes (adjusted HRs were 1.79 [95% CI, 1.21 to 2.66] and 1.87 [95% CI, 1.22 to 2.88] in central obese action levels 1 and 2) than the WC-WHO. The combination of the BMI-Asian/Hong Kong with WC-China demonstrated the strongest prediction. There were no gender differences in the impact of adiposity on diabetes.Conclusion: In older Chinese, BMI-Asian/Hong Kong criteria is a better predictor of diabetes than other BMI criterion. Its combination with WC-China improved the prediction of adiposity to diabetes, which would help manage bodyweight in older age to reduce the risk of diabetes.

The purpose of this study is to explore the association between adiposity indices and blood lipid indices and prediabetes. We compare the predictive value of new adiposity indices and traditional adiposity indices and blood lipid indices in the diagnosis of prediabetes.This is a prospective cohort study of 7953 participants. The follow-up time was 3 years. The eight adiposity indices included the following: body mass index (BMI), waist circumference (WC), body roundness index (BRI), A Body Shape Index (ABSI), visceral adiposity index (VAI), lipid accumulation product (LAP), fatty liver index (FLI), and triglyceride-to-glucose fasting index (TyG), as well as four blood lipid indices as follows: total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C).The association between adiposity indices and blood lipid indices for diagnosis of prediabetes was estimated using a logistic regression model to obtain the odds ratio (OR) and its 95% confidence interval (CI). We calculated the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis to measure the predictive value of adiposity indices and blood lipid indicators for the diagnosis of prediabetes in the general population stratified by gender.The median age of the participants was 56 years old, men accounting for 35.3% of the final group. After adjusting for confounding factors, association of BMI, BRI, VAI, LAP, TyG, TC, TG, and LDL-C with prediabetes status was assessed at both baseline and follow-up. TyG (AUC, overall: 0.677 (95% CI, 0.665, 0.689), male: 0.645 (95% CI, 0.624-0.667), and female: 0.693 (95% CI, 0.678-0.708)) have better diagnostic value for prediabetes than VAI, LAP, FLI, TC, TG, HDL-C, and LDL-C. The predictive value of the combination of TyG, BRI, VAI, and TG significantly improves the power of any single index in the diagnosis of prediabetes. The AUC and corresponding 95% CI of TyG, BRI, VAI, and TG and the combination of these four indicators to diagnose prediabetes were 0.677 (0.665, 0.689), 0.630 (0.617, 0.643), 0.618 (0.606, 0.631), 0.622 (0.609, 0.635), and 0.728 (0.716, 0.739), respectively.Among the eight adiposity indices and four blood lipid indices evaluated in the study, TyG had the highest diagnostic value for prediabetes in isolated indexes, and the combination of TyG, BRI, VAI, and TG significantly improved the diagnostic value for prediabetes of any single indicator.

It has been established that for youth without disabilities, muscular strength (MS) is negatively associated with total and central adiposity. However, this relationship has not been clearly established for youth with intellectual disability (ID). The purpose of this study was to examine the association of MS with total and central adiposity in adolescents with ID.Participants were 59 adolescents (40 males and 19 females: age 16.29 ± 1.66 years) with ID. Total and central adiposity were evaluated with dual-energy x-ray absorptiometry (DXA), body mass index (BMI), BMI z-score, waist circumference (WC), and conicity index (C-index). MS was evaluated with the score on the Bruininks-Oseretsky Test of Motor Proficiency (range, 0 to 42, with higher scores indicating better performance). Sex-specific maturity offset equations were used to evaluate somatic maturity. Spearman's correlation coefficients and sequential multiple regression were used to examine associations between MS and adiposity.Muscular strength score was negatively associated with BMI (sr = -0.32; P 0.05), percent body fat (%BF; total, trunk, android and gynoid regions) (sr = -0.51 to -0.58; P 0.01), and android-to-gynoid fat ratio (sr = -0.29; P 0.05). After control for somatic maturity and sex, regression analysis indicated that MS score explained 10%-17% of the variance in BMI, BMI z-score, %BF (total, trunk, android and gynoid regions), WC, C-index and android-to-gynoid fat ratio.These findings suggest that MS is associated with DXA- and anthropometric-determined total and central adiposity among adolescents with ID.

The visceral adiposity index (VAI) has been recently established as a measure of visceral fat distribution and is shown to be associated with a wide range of adverse health events. However, the precise associations between the VAI score and all-cause and cause-specific mortalities in the general population remain undetermined.In this large-scale prospective epidemiological study, 357,457 participants (aged 38-73 years) were selected from the UK Biobank. We used Cox competing risk regression models to estimate the association between the VAI score and all-cause, cardiovascular disease (CVD), cancer, and other mortalities. The VAI score was significantly correlated with an increased risk of all-cause mortality (hazard ratio [HR], 1.200; 95% confidence interval [CI], 1.148-1.255; P 0.0001), cancer mortality (HR, 1.224; 95% CI, 1.150-1.303; P 0.0001), CVD mortality (HR, 1.459; 95% CI, 1.148-1.255; P 0.0001), and other mortalities (HR, 1.200; 95% CI, 1.148-1.255; P 0.0001) after adjusting for a series of confounders. In addition, the subgroup analyses showed that HRs were significantly higher in participants who were male, aged below 65 years, and body mass index less than 25.In summary, VAI was positively associated with an increased risk of all-cause and cause-specific mortalities in a nationwide, well-characterised population identified in a UK Biobank. The VAI score might be a complementary traditional predictive indicator for evaluating the risk of adverse health events in the population of Western adults aged 38 years and older.

The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. Graphical abstract Irisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model

This study aimed to examine the effects of substituting sedentary time with sleep or physical activity on adiposity in a longitudinal sample of adolescents.Adolescents (10-16 yr) were recruited for a prospective observational cohort. Parents and adolescents reported demographic characteristics and pubertal development. Accelerometry was used to measure sleep, physical activity, and sedentary time. Adiposity was quantified with imaging techniques. Isotemporal substitution modeling was conducted to examine the effect of substituting 10 min of sedentary time with sleep or differing intensities of physical activity. Results were stratified by sex and race and adjusted for covariates.A total of 217 adolescents provided complete measures at both baseline and 2 yr later (58.1% White, 51.8% girls; 12.9 ± 1.9 yr at baseline). Sleep was negatively related to adiposity 2 yr later when considering other movement behaviors, but substituting baseline sedentary time with sleep was not related to future adiposity ( P0.05). In boys and non-White adolescents, substituting sedentary time with vigorous-intensity physical activity was related to lower adiposity 2 yr later ( P0.05). Substituting sedentary time for moderate- to vigorous-intensity physical activity was not associated with future adiposity.Substituting sedentary time with vigorous-intensity physical activity was related to lower adiposity in later adolescence in certain groups. Opportunities to promote an adequate balance of sleep, sedentary time, and physical activity in all adolescents are encouraged for optimal development.

Background Paradoxical adipose hyperplasia (PAH), a rare side effect of CoolSculpting (cryolipolysis), is characterized by fatty enlargement of the treatment area occurring months after the procedure. Objectives The purpose of this study was to report a retrospective case series of patients diagnosed with PAH at the authors’ institution, increase the collective understanding of this complication and subsequent management, and raise the question of who should ethically perform cryolipolysis. Methods All participants diagnosed with PAH by a plastic surgeon at a large academic medical center were identified. Demographic information, medical history, procedure details, time to PAH diagnosis, and corrective surgical intervention details were collected. Mean duration of time from cryolipolysis treatment to diagnosis of PAH was calculated, along with other descriptive statistics. A scoping review of all PAH literature published in PubMed, Embase, and Web of Science was also conducted. Results Four patients diagnosed with PAH after cryolipolysis were identified for inclusion in this study. The calculated incidence of PAH at our center was 0.67%. All patients requested therapy for PAH and subsequently underwent either liposuction, abdominoplasty, or both. The mean duration of in-person follow-up time after final surgical treatment of PAH was 13.8 + 19.8 months (range, 2.8-43.5). Fortunately, no patients showed signs of PAH recurrence, and 3 out of 4 patients did not show signs of residual deformity. Conclusions Findings from this patient cohort and scoping review provide evidence that although revisions may be required, conventional body contouring methods, not in the armamentarium of non-plastic surgeon practitioners, effectively alleviated PAH. Level of Evidence: 4

An inverse relationship between vitamin D (VD) nutritional status and obesity is frequent, and the distribution of body fat is an important aspect to assess the risks of obesity-related metabolic dysfunction. The purpose of the study was to evaluate the relationship between serum VD concentrations and body fat reduction after 12 months of bariatric surgery, using two different vitamin D3 (VD3) supplementation protocols.A randomized controlled trial consisted of 41 patients divided into G1 (800 IU/day) and G2 (1800 IU/day) according to the VD3 supplementation. At baseline (T0) and follow-up (T1), 25(OH)D, waist circumference (WC), visceral adiposity index (VAI), body adiposity index (BAI), and waist/height ratio (WHtR) were evaluated.In T0, the mean of 25(OH)D was lower in G2 compared to that in G1 (22.6 vs 23.6 ng/mL; p = 0.000). At T1, it had a significant increase in G2 (32.1 vs 29.9 ng/mL; p = 0.000), with 60% sufficiency. A significant negative correlation was observed between VAI, BAI, and WHtR with 25(OH)D in G2 (r = - 0.746, p = 0.024; r = - 0.411, p = 0.036; r = - 0.441, p = 0.032) after surgery. Higher mean changes from baseline of visceral fat loss, represented by VAI, were observed in G2 (176.2 ± 149.0-75.5 ± 55.0, p = 0.000).Patients submitted to the 1800 IU/day protocol, 12 months after the surgical procedure, had a higher percentage of sufficient vitamin D levels compared to those submitted to the 800 IU/day protocol. Additionally, higher dose supplementation promoted a significant improvement in VAI.

OBJECTIVE: Ultraprocessed food (UPF) intake is associated with BMI, but effects on regional adipose depots or related to minimally processed food (MPF) intake are unknown. METHODS: Data included 12,297 adults in the National Health and Nutrition Examination Survey (NHANES), 2011 to 2016. This study analyzed associations between usual percentage of kilocalories from UPFs and MPFs and three adiposity indicators: supine sagittal abdominal diameter to height ratio (SADHtR, estimates visceral adiposity); waist circumference to height ratio (WHtR, estimates abdominal adiposity); and BMI, using linear and multinomial logistic regression. RESULTS: Standardized β coefficients per 10% increase in UPF intake were 0.0926, 0.0846, and 0.0791 for SADHtR, WHtR, and BMI, respectively (all p < 0.001; p > 0.26 for pairwise differences). For MPF intake, the β coefficients were −0.0901, −0.0806, and −0.0688 (all p < 0.001; p > 0.18 pairwise). Adjusted odds ratios (95% CI) for adiposity tertile 3 versus tertile 1 (comparing UPF intake quartiles 2, 3, and 4 to quartile 1) were 1.33 (1.22-1.45), 1.67 (1.43-1.95), and 2.24 (1.76-2.86), respectively, for SADHtR; 1.31 (1.19-1.44), 1.62 (1.37-1.91), and 2.13 (1.63-2.78), respectively, for WHtR; and 1.27 (1.16-1.39), 1.53 (1.31-1.79), and 1.96 (1.53-2.51), respectively, for BMI. MPF intake showed inverse associations with similar trends in association strength. CONCLUSIONS: Among US adults, abdominal and visceral adiposity indictors were positively associated with UPFs and inversely associated with MPFs.

Growth abnormalities in childhood have been related to later cardiometabolic risks, but little is known about these associations in populations at high risk of type 2 diabetes.We examined the associations of patterns of growth, including weight and height at ages 1-59 months, with cardiometabolic risk factors at ages 5-16 years.We linked anthropometric data collected at ages 1-59 months to cardiometabolic data obtained from a longitudinal study in a southwestern American Indian population at high risk of diabetes. Analyses included 701 children with ≥1 follow-up examination at ages 5-16 years. We derived age- and sex-specific weight-for-height z-scores (WHZ) and height-for-age z-scores (HAZ) at ages 1-59 months. We selected the highest observed WHZ and the lowest observed HAZ at ages 1-59 months and analyzed associations of z-scores and categories of WHZ and HAZ with cardiometabolic outcomes at ages 5-16 years. We used linear mixed-effects models to account for repeated measures.Overweight/obesity (WHZ 2) at ages 1-59 months was significantly associated with increased BMI, fasting and 2-hour postload plasma glucose, fasting and 2-hour insulin, triglycerides, systolic blood pressure, diastolic blood pressure, and decreased HDL cholesterol at ages 5-16 years relative to normal weight (WHZ ≤1). For example, at ages 5-9 years, 2-hour glucose was 10.4 mg/dL higher (95% CI: 5.6-15.3 mg/dL) and fasting insulin was 4.29 μU/mL higher (95% CI: 2.96-5.71 μU/mL) in those with overweight/obesity in early childhood. Associations were attenuated and no longer significant when adjusted for concurrent BMI. A low height-for-age (HAZ-2) at ages 1-59 months was associated with 5.37 mg/dL lower HDL (95% CI: 2.57-8.17 mg/dL) and 27.5 μU/mL higher 2-hour insulin (95% CI: 3.41-57.6 μU/mL) at ages 10-16 years relative to an HAZ ≥0.In this American Indian population, findings suggest a strong contribution of overweight/obesity in early childhood to cardiometabolic risks in later childhood and adolescence, mediated through persistent overweight/obesity into later ages. Findings also suggest potential adverse effects of low height-for-age, which require confirmation.

Aim: of this paper is to review the recent literature on the relationship between ectopic fat accumulation and cardiovascular disease. Data synthesis: Ectopic fat is an important predictor of metabolic (in particular insulin resistance) and cardiovascular disease, carrying more risk than general fat accumulation. Recent studies have shown a link between ectopic fat accumulation, as cardiac (epicardial or intra-myocardial fat) and/or visceral and/or hepatic fat, and development of atherosclerosis, coronary heart disease and hypertension. Conclusions: Ectopic fat accumulation is not only a marker of cardiometabolic disease, since through the release of adipocitokines, lipotoxic and glucotoxic agents, participates in the crosstalk with insulin-sensitive organs leading to metabolic, cardiac and vascular dysfunctions., This article version may be used for non-commercial purposes in accordance with CC BY-NC-ND license terms and conditions.

Sex is a key risk factor for many types of cardiovascular disease. It is imperative to understand the mechanisms underlying sex differences to devise optimal preventive and therapeutic approaches for all individuals. Both biological sex (determined by sex chromosomes and gonadal hormones) and gender (social and cultural behaviors associated with femininity or masculinity) influence differences between men and women in disease susceptibility and pathology. Here, we focus on the application of experimental mouse models that elucidate the influence of 2 components of biological sex—sex chromosome complement (XX or XY) and gonad type (ovaries or testes). These models have revealed that in addition to well-known effects of gonadal hormones, sex chromosome complement influences cardiovascular risk factors, such as plasma cholesterol levels and adiposity, as well as the development of atherosclerosis and pulmonary hypertension. One mechanism by which sex chromosome dosage influences cardiometabolic traits is through sex-biased expression of X chromosome genes that escape X inactivation. These include chromatin-modifying enzymes that regulate gene expression throughout the genome. The identification of factors that determine sex-biased gene expression and cardiometabolic traits will expand our mechanistic understanding of cardiovascular disease processes and provide insight into sex differences that remain throughout the lifespan as gonadal hormone levels alter with age.

A busca pelo corpo ideal e a exigência da mídia quanto aos padrões de beleza fazem com que a sociedade procure clínicas de estética para a redução da gordura localizada. Diante desse cenário, o estudo tem como objetivo buscar informações das possíveis interpretações dadas pelos diferentes autores em relação aos procedimentos estéticos que tratam a gordura localizada, deixando, como última opção, as cirurgias plásticas pelo seu grau de invasividade e possibilidades de complicações. A fim de alcançar os objetivos utilizou-se a revisão bibliográfica como ferramenta de revisão especializada. Foram captados artigos das bases de dados eletrônicosScientific Electronic Library Online(SciELO) e LILACS, como também foi utilizado o buscador Google Acadêmico. Os resultados da pesquisa dos artigos obtiveram um total de 45 artigos analisados, sendo que apenas 28 foram utilizados na pesquisa, pois estavam dentro dos critérios de inclusão/exclusão elencados na metodologia da pesquisa. Diante deste estudo observou-se a importância de realizar tais procedimentos estéticos com profissionais capacitados.&nbsp

AimsAlthough highly heritable, the genetic etiology of calcific aortic stenosis (AS) remains incompletely understood. The aim of this study was to discover novel genetic contributors to AS and to integrate functional, expression, and cross-phenotype data to identify mechanisms of AS.Methods and resultsA genome-wide meta-analysis of 11.6 million variants in 10 cohorts involving 653 867 European ancestry participants (13 765 cases) was performed. Seventeen loci were associated with AS at P ≤ 5 × 10-8, of which 15 replicated in an independent cohort of 90 828 participants (7111 cases), including CELSR2-SORT1, NLRP6, and SMC2. A genetic risk score comprised of the index variants was associated with AS [odds ratio (OR) per standard deviation, 1.31; 95% confidence interval (CI), 1.26-1.35; P = 2.7 × 10-51] and aortic valve calcium (OR per standard deviation, 1.22; 95% CI, 1.08-1.37; P = 1.4 × 10-3), after adjustment for known risk factors. A phenome-wide association study indicated multiple associations with coronary artery disease, apolipoprotein B, and triglycerides. Mendelian randomization supported a causal role for apolipoprotein B-containing lipoprotein particles in AS (OR per g/L of apolipoprotein B, 3.85; 95% CI, 2.90-5.12; P = 2.1 × 10-20) and replicated previous findings of causality for lipoprotein(a) (OR per natural logarithm, 1.20; 95% CI, 1.17-1.23; P = 4.8 × 10-73) and body mass index (OR per kg/m2, 1.07; 95% CI, 1.05-1.9; P = 1.9 × 10-12). Colocalization analyses using the GTEx database identified a role for differential expression of the genes LPA, SORT1, ACTR2, NOTCH4, IL6R, and FADS.ConclusionDyslipidemia, inflammation, calcification, and adiposity play important roles in the etiology of AS, implicating novel treatments and prevention strategies.

AIMS: Reduced lung function is associated with an adverse metabolic risk profile, even after adjusting for body fatness. However, previous observations may have been confounded by aerobic fitness and physical activity. This study aimed to examine the association between lung function and both metabolic risk and insulin resistance in a cohort of White British adults with a family history of Type 2 diabetes, and to explore the extent to which these associations are independent of body fatness, aerobic fitness (VO(2max)) and objectively measured physical activity. METHODS: Adults (n = 320, mean age 40.4 +/- 6.0 years) underwent measurement of physical activity energy expenditure (PAEE), spirometry [forced expiratory volume in 1 s (FEV(1))] and forced vital capacity (FVC), aerobic fitness (predicted VO(2max)), and anthropometric and metabolic status at baseline and again after 1 year (n = 257) in the ProActive trial. Clustered metabolic risk was calculated by summing standardized values for triglycerides, fasting insulin, fasting glucose, blood pressure and the inverse of high-density lipoprotein-cholesterol. A cross-sectional analysis using linear regression with repeated measures was performed. RESULTS: Both FEV(1) and FVC were inversely and statistically significantly associated with metabolic risk and insulin resistance after adjusting for age, sex, smoking status, height, PAEE and fitness. The associations with metabolic risk remained significant after adjusting for measures of body fatness, but those with insulin resistance did not. CONCLUSIONS: Reduced lung function was associated with increased metabolic risk in this cohort of carefully characterized at-risk individuals. This association was independent of overall and central body fatness, objectively measured physical activity and aerobic fitness.

Background: Obesity is a heritable complex phenotype that can increase the risk of age-related outcomes. Biological age can be estimated from DNA methylation (DNAm) using various “epigenetic clocks.” Previous work suggests individuals with elevated weight also display accelerated aging, but results vary by epigenetic clock and population. Here, we utilize the new epigenetic clock GrimAge, which closely correlates with mortality. Objectives: We aimed to assess the cross-sectional association of body mass index (BMI) with age acceleration in twins to limit confounding by genetics and shared environment. Methods and results: Participants were from the Finnish Twin Cohort (FTC; n = 1424), including monozygotic (MZ) and dizygotic (DZ) twin pairs, and DNAm was measured using the Illumina 450K array. Multivariate linear mixed effects models including MZ and DZ twins showed an accelerated epigenetic age of 1.02 months (p-value = 6.1 × 10–12) per one-unit BMI increase. Additionally, heavier twins in a BMI-discordant MZ twin pair (ΔBMI >3 kg/m2) had an epigenetic age 5.2 months older than their lighter cotwin (p-value = 0.0074). We also found a positive association between log (homeostatic model assessment of insulin resistance) and age acceleration, confirmed by a meta-analysis of the FTC and two other Finnish cohorts (overall effect = 0.45 years, p-value = 4.1 × 10–25) from adjusted models. Conclusion: We identified significant associations of BMI and insulin resistance with age acceleration based on GrimAge, which were not due to genetic effects on BMI and aging. Overall, these results support a role of BMI in aging, potentially in part due to the effects of insulin resistance. publishedVersion

As the proportion of visceral (VAT) to subcutaneous adipose tissue (SAT) may contribute to type 2 diabetes (T2D) development, we examined this relation in a cross-sectional design within the Multiethnic Cohort that includes Japanese Americans known to have high VAT. The aim was to understand how ectopic fat accumulation differs by glycemic status across ethnic groups with disparate rates of obesity, T2D, and propensity to accumulate VAT.In 2013-2016, 1,746 participants aged 69.2 (standard deviation, 2.7) years from five ethnic groups completed questionnaires, blood collections, and whole-body dual X-ray absorptiometry and abdominal magnetic resonance imaging scans. Participants with self-reported T2D and/or medication were classified as T2D, those with fasting glucose125 and 100-125 mg/dL as undiagnosed cases (UT2D) and prediabetes (PT2D), respectively. Using linear regression, we estimated adjusted means of adiposity measures by T2D status.Overall, 315 (18%) participants were classified as T2D, 158 (9%) as UT2D, 518 (30%) as PT2D, and 755 (43%) as normoglycemic (NG), with significant ethnic differences (P0.0001). In fully adjusted models, VAT, VAT/SAT, and percent liver fat increased significantly from NG, PT2D, UT2D, to T2D (P0.001). Across ethnic groups, the VAT/SAT ratio was lowest for NG participants and highest for T2D cases. Positive trends were observed in all groups except African Americans, with highest VAT/SAT in Japanese Americans.These findings indicate that VAT plays an important role in T2D etiology, in particular among Japanese Americans with high levels of ectopic adipose tissue, which drives the development of T2D to a greater degree than in other ethnic groups.

Epicardial adipose tissue (EAT) has been proposed to be an independent predictor of visceral adiposity. EAT measures are associated with coronary artery disease, diabetes, and chronic obstructive pulmonary disease, which are risk factors for COVID-19 poor prognosis. Whether EAT measures are related to COVID-19 severity and prognosis is controversial.We searched 6 databases for studies until January 7, 2022. The pooled effects are presented as the standard mean difference (SMD) or weighted mean difference with 95% confidence intervals (CIs). The primary end point was COVID-19 severity. Adverse clinical outcomes were also assessed.A total of 13 studies with 2482 patients with COVID-19 were identified. All patients had positive reverse transcriptase-polymerase chain reaction results. All quantitative EAT measures were based on computed tomography. Patients in the severe group had higher EAT measures compared with the nonsevere group (SMD = 0.74, 95% CI: 0.29-1.18, P = 0.001). Patients with hospitalization requirement, requiring invasive mechanical ventilation, admitted to intensive care unit, or with combined adverse outcomes had higher EAT measures compared to their controls (all P0.001).EAT measures were associated with the severity and adverse clinical outcomes of COVID-19. EAT measures might help in prognostic risk stratification of patients with COVID-19.

This article aims to critically overview the current interplay of genetic/epigenetic factors and several nutritional aspects influencing obesity susceptibility and adiposity outcomes for obesity management and weight status monitoring.Single nucleotide polymorphisms located in or near genes participating in energy homeostasis, fatty acid metabolism, appetite control, brain regulation, and thermogenesis have been associated with body composition measures (body weight, body mass index, waist circumference, body fat percentage, and visceral adipose tissue) depending on nutrient intakes, dietary patterns, and eating behaviors. Moreover, studies analyzing interactions between the epigenome and dietary intakes in relation to adiposity outcomes are reported. The main epigenetic mechanisms include methylation levels of promoter sequences, telomere length, and micro-ribonucleic acid expression profiles, whereas covalent histone modifications remain less studied.Exploring potential interactions between the genetic/epigenetic background and nutritional features is improving the current understanding of the obesity physiopathogenesis and the usefulness of translating this precision information in the clinical setting for weight gain prediction, the design of personalized nutrition therapies as well as individual responsiveness estimation to dietary advice. The analysis of further relationships between the genotype, the epigenotype and other precision markers including the gut microbiota and the metabolome is warranted.

Observational studies reveal that different body fat measures are associated with cardiometabolic disease with different effects. However, causality is not reflected by such observations. To explore and compare the causal relationships of general obesity (measured by body mass index (BMI)), adipose obesity (measured by fat mass percentage (FMP)) and central obesity (measured by waist-to-height ratio (WHtR)) with cardiometabolic traits among children.We conducted one sample Mendelian randomization (MR) analysis in 3266 children from Beijing Children and Adolescents Metabolic Syndrome Study. Genetic instruments based on 28 SNPs were performed to explore and compare the causal associations of genetically BMI, FMP and WHtR with cardiometabolic traits. The genetic instruments were robustly correlated with observed BMI, FMP and WHtR. Each genetically 1-SD increment in BMI, FMP and WHtR were causally associated with increment in systolic blood pressure (SBP), diastolic blood pressure (DBP), log-transformed fasting plasma glucose (FPG), log-transformed HOMA-β, and decrease in log-transformed high-density lipoprotein cholesterol (HDL), respectively (all P 0.05 after Bonferroni correction). The receiver operating characteristic curve indicated that BMI and FMP showed stronger effects on SBP, DBP, HOMA-β and HDL than WHtR (all P 0.05). We also observed causal associations of BMI and FMP with log-transformed fasting insulin and HOMA-IR.The MR analysis based on population-based cohort indicated a causal relationship of adiposity and body fat distribution with cardiometabolic traits. When compared with central obesity, general obesity and adipose obesity might own stronger effects on blood pressure and blood lipids among children.

Nutritional status can change in breast cancer patients after treatment. However, the metabolic implications of those alterations are poorly understood. We used a cross-sectional study design to compare body composition, lipids, glucose levels, and adiposity indices in breast cancer patients with a matched control and a healthy group. We recruited women who completed their chemotherapy (BC group) and compared them with a group of women without cancer age and body mass index-paired (MC group) and a group of healthy women (HC group). We estimated body composition by bioelectrical impedance analysis, physical function by handgrip strength, and food consumption by 24-hour food record. A blood sample was collected. We calculated visceral obesity indices (VAI and LAP) and insulin resistance-triglyceride glucose (TyG). Eighty-eight women were included (BC = 36, MC = 36, HC = 16). BC patients demonstrated worse phase angle values, nutritional risk index and lower handgrip strength. Additionally, according to the indices, BC had impairments in lipids, worse glucose levels, and elevated visceral fat adiposity and presented important unhealthy dietary patterns characterized by under-recommended protein consumption and higher caloric intake than the other groups. No differences were observed between both control groups. Further investigations are required to examine the underlying mechanisms and the potential longitudinal changes during surveillance.

Prior studies have suggested reciprocal relationships between cognitive function and adiposity, but this has not been investigated with population representative data sets. The purpose of this study was to examine the association between cognitive function and adiposity in a large population-based sample of middle-aged and older adults. It was hypothesized that better scores on tests of cognitive function would be associated with lower adiposity, and this association would be primarily mediated through life-style behavior and physical health status.Using baseline data from the Canadian Longitudinal Study on Aging ( N = 30,097), we tested our hypotheses using three indicators of cognitive function (animal fluency, Stroop interference, and reaction time) and four indicators of adiposity (body mass index, total fat mass, waist circumference, and waist-hip ratio). Hierarchical multivariable linear regression modeling was conducted followed by tests for moderation by socioeconomic status and mediation through diet, physical activity, hypertension, and diabetes status.All measures of cognitive indicators were significantly associated with adiposity after adjusting for confounders. In general, superior performance on animal fluency, Stroop, and reaction time tasks were associated with lower adiposity by most metrics. Stroop interference was associated with lower adiposity across all metrics, including body mass index ( b = - 0.04, 95 % confidence interval [CI] = - 0.06 to - 0.01), total fat mass ( b = 19.35, 95 % CI = 8.57 to 30.12), waist circumference ( b = 33.83, 95 % CI = 10.08 to 57.58), and waist-hip ratio ( b = 0.13, 95 % CI = 0.01 to 0.24). These associations were more substantial for moderate- and high-income subpopulations. Mediation analyses suggested that the aforementioned effects were mediated through life-style behavior (e.g., diet and physical activity) and physical health conditions (e.g., diabetes and hypertension).Reliable associations exist between cognitive function and adiposity in middle-aged and older adults. The associations seem to be mediated through life-style behavior and physical health conditions.

Childhood obesity is a global health concern, with340 million youth considered overweight or obese. In addition to contributing greatly to health care costs, excess adiposity associated with obesity is considered a major risk factor for premature mortality from cardiovascular and metabolic diseases and is also negatively associated with cognitive and brain health. A complementary line of research highlights the importance of cardiorespiratory fitness, a by-product of engaging in physical activity, on an abundance of health factors, including cognitive and brain health.This study investigated the relationship among excess adiposity (visceral adipose tissue [VAT], subcutaneous abdominal adipose tissue), total abdominal adipose tissue, whole-body percent fat [WB%FAT], body mass index (BMI), and fat-free cardiorespiratory fitness (FF-V̇O 2max ) on resting-state functional connectivity (RSFC) in 121 ( f = 68) children (7-11 yr) using a data-driven whole-brain multivoxel pattern analysis.Multivoxel pattern analysis revealed brain regions that were significantly associated with VAT, BMI, WB%FAT, and FF-V̇O 2 measures. Yeo's (2011) RSFC-based seven-network cerebral cortical parcellation was used for labeling the results . Post hoc seed-to-voxel analyses found robust negative correlations of VAT and BMI with areas involved in the visual, somatosensory, dorsal attention, ventral attention, limbic, frontoparietal, and default mode networks. Further, positive correlations of FF-V̇O 2 were observed with areas involved in the ventral attention and frontoparietal networks. These novel findings indicate that negative health factors in childhood may be selectively and negatively associated with the 7 Yeo-defined functional networks, yet positive health factors (FF-V̇O 2 ) may be positively associated with these networks.These novel results extend the current literature to suggest that BMI and adiposity are negatively associated with, and cardiorespiratory fitness (corrected for fat-free mass) is positively associated with, RSFC networks in children.

Background The roles of individual and co-regulated lipid molecular species in the development of type 2 diabetes (T2D) and mediation from metabolic risk factors remain unknown. Methods We conducted profiling of 166 plasma lipid species in 2 nested case-control studies within 2 independent cohorts of Chinese adults, the Dongfeng-Tongji and the Jiangsu non-communicable disease cohorts. After 4.61 (0.15) and 7.57 (1.13) years’ follow-up, 1039 and 520 eligible participants developed T2D in these 2 cohorts, respectively, and controls were 1:1 matched to cases by age and sex. Results We found 27 lipid species, including 10 novel ones, consistently associated with T2D risk in the 2 cohorts. Differential correlation network analysis revealed significant correlations of triacylglycerol (TAG) 50:3, containing at least one oleyl chain, with 6 TAGs, at least 3 of which contain the palmitoyl chain, all downregulated within cases relative to controls among the 27 lipids in both cohorts, while the networks also both identified the oleyl chain-containing TAG 50:3 as the central hub. We further found that 13 of the 27 lipids consistently mediated the association between adiposity indicators (body mass index, waist circumference, and waist-to-height ratio) and diabetes risk in both cohorts (all P Conclusions Our findings suggested notable perturbed co-regulation, inferred from differential correlation networks, between oleyl chain- and palmitoyl chain-containing TAGs before diabetes onset, with the oleyl chain-containing TAG 50:3 at the center, and provided novel etiological insight regarding lipid dysregulation in the progression from adiposity to overt T2D.

Australian children consume 35% of energy from discretionary food and beverages which increases their risk of non-communicable diseases like type 2 diabetes. Despite this concerning statistic, broad analysis of the profile of discretionary food intake has not been fully undertaken. This study asks: what is the discretionary food and beverage intake profile, contribution to nutrient intakes, and associations with demographic and health characteristics?Cross-sectional data from the 2011-12 National Nutrition and Physical Activity Survey (n = 2812, 2-18 years) were used to profile discretionary food consumption. Dietary intake was assessed by 24-h recall. General linear models tested the difference in respondent characteristics by age group, sex, and quartiles of discretionary food energy contribution.Ninety-nine percent of respondents consumed discretionary foods, 74% exceeded the maximum discretionary food recommended serves. Among 10 eating occasions available to select: snack, dinner, lunch and morning tea appeared to contribute 76% of discretionary food energy, with snack and dinner contributing 24% each. Age and frequency of discretionary food consumption were positively associated with energy intake from discretionary foods (p 0.001); while sex, socio-economic status, physical activity and body composition had no association. High discretionary food consumers chose specific discretionary food items in a large quantity (1.0-3.5-serves/discretionary food) compared to low discretionary food consumers (0.4-1.4-serves/discretionary food).Nearly all Australian children and adolescents consumed discretionary food daily. No demographic or anthropometric characteristics beyond increasing age were associated with higher discretionary food. Targeted public health policy and community interventions are required to focus on addressing the largest contributors to discretionary food intake in terms of equivalent serve sizes, popularity, and eating occasion.

Although several factors such as respiratory muscle strength, lung compliance, resistance to airflow, and even obesity affect the lung functions, the nature of relationship with markers of adiposity is not clear. We hypothesised that central pattern of fat distribution is a significant predictor of decreased peak expiratory flow rate (PEFR). The present study was designed with the aim to examine the effects of adiposity on PEFR in males.One hundred young healthy male volunteers were analysed in the study. They were classified into non-obese, and obese groups based on body mass index (BMI) (obeseor = 30 Kg/m2 and non-obese30 Kg/m2). The PEFR was measured by using Wright's peak flow meter. Data was analysed using unpaired 't' test for statistical significance of differences between the non-obese and the obese, stratified into age groups of 20 to 30 years and 30 to 40 years. A partial correlation adjusted to age, height and BMI followed by regression analysis was conducted using adiposity markers as a predictor of PEFR.The model adjusted to age, height, weight and BMI revealed waist hip ratio (WHR) as the only parameter which shows significant variance in PEFR with a Pearson's r=-0.59, F (1, 100)=12.23, p=0.04. The resulting linear regression equation is y=-388.72xWHR+850.68.Our findings suggest that obesity itself and especially the pattern of body fat distribution have independent effects on PEFR. These results suggest that abdominal adiposity, measured as WHR, is a better predictor of expiratory flow than weight or BMI.

Efforts to reveal the direction of influence between physical activity (PA), sedentary time (ST) and body fat in youth have produced inconsistent results, possibly due to a lack of adjustment for confounders and other factors. Sex-specific associations have rarely been studied.A sample from two Norwegian birth cohorts (n = 809) were followed biennially over five waves from the age of 6-14 years. Physical activity and ST were recorded by accelerometers, and body fat was assessed by bioelectrical impedance measurements.By applying a dynamic panel model (DPM) that adjusts for all time-invariant confounding factors, it was found that among boys, increased fat mass index (FMI) at ages 8, 10 and 12 years predicted decreased PA two years later (8-10 years: B = -0.67, (95% CI: -1.1, -0.24); 10-12 years: B = -0.33, (95% CI: -0.61, -0.05); 12-14 years: B = -0.29, (95% CI: -0.52, -0.06)). Regarding the opposite direction of influence, more PA at age 12 forecasted reduced FMI at age 14 (B = -0.16, (95% CI: -0.24, -0.07)), whereas increased FMI predicted increased ST across all time points in boys only (6-8 years: B = 0.23, (95% CI:0.02.43); 8-10 years: B = 0.23, (95% CI:.08.39); 10-12 years: B = 0.13, (95% CI:.03.23); 12-14 years: B = 0.17, (95% CI:.07, 26)). The revealed relationships were significantly stronger in boys compared to the (absent) relations in girls. Sensitivity analyses examining moderate to vigorous PA (MVPA) rather than total PA were in accordance with the main findings.In boys, increased FMI predicted reduced PA and increased ST two years later from childhood to adolescence. The opposite direction of influence was evident from only ages 12-14. There were no prospective relationships between FMI and PA or ST among girls.

The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort.We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up.The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (0.02 kg/mBMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background.

BACKGROUND AND AIMS: Obesity is one of the leading causes of non-communicable diseases (NCD). Thus, NCD risk varies in obese individuals based on the location of their fat depots; while subcutaneous adiposity is protective, visceral adiposity increases NCD risk. Although, previously anthropometric traits have been used to quantify body shape in low-income settings, there is no consensus on how it should be assessed. Hence, there is a growing interest to evaluate body shape derived from the principal component analysis (PCA) of anthropometric traits; however, this is yet to be explored in individuals of African ancestry whose body shape is different from those of Europeans. We set out to capture body shape in its multidimensional structure and examine the association between genetic variants and body shape in individuals of African ancestry. METHOD AND RESULTS: We performed a genome-wide association study (GWAS) for body shape derived from PCA analysis of anthropometric traits in the Ugandan General Population Cohort (GPC, n = 6407) and the South African Zulu Cohort (SZC, n = 2595), followed by a GWAS meta-analysis to assess the genetic variants associated with body shape. We identified variants in FGF12, GRM8, TLX1NB and TRAP1 to be associated with body shape. These genes were different from the genes been associated with BMI, height, weight, WC and waist-hip ration in continental Africans. Notably, we also observed that a standard deviation change in body shape was associated with an increase in blood pressure and blood lipids. CONCLUSION: Variants associated with body shape, as a composite variable might be different for those of individual anthropometric traits. Larger studies are required to further explore these phenomena.

Transcriptomic analysis in metabolically active tissues allows a systems genetics approach to identify causal genes and networks involved in metabolic disease. Outbred heterogeneous stock (HS) rats are used for genetic mapping of complex traits, but to-date, a systems genetics analysis of metabolic tissues has not been done. We investigated whether adiposity-associated genes and gene co-expression networks in outbred heterogeneous stock (HS) rats overlap those found in humans. We analyzed RNAseq data from adipose tissue of 415 male HS rats, correlated these transcripts with body weight (BW) and compared transcriptome signatures to two human cohorts: the African American Genetics of Metabolism and Expression and Metabolic Syndrome in Men. We used weighted gene co-expression network analysis to identify adiposity-associated gene networks and mediation analysis to identify genes under genetic control whose expression drives adiposity. We identified 554 orthologous “consensus genes” whose expression correlates with BW in the rat and with body mass index (BMI) in both human cohorts. Consensus genes fell within eight co-expressed networks and were enriched for genes involved in immune system function, cell growth, extracellular matrix organization and lipid metabolic processes. We identified 19 consensus genes for which genetic variation may influence BW via their expression, including those involved in lipolysis (e.g., Hcar1), inflammation (e.g., Rgs1), adipogenesis (e.g., Tmem120b) or no previously known role in obesity (e.g., St14, Msa4a6). Strong concordance between HS rat and human BW/BMI associated transcripts demonstrates translational utility of the rat model, while identification of novel genes expands our knowledge of the genetics underlying obesity.

Diabetes is a metabolic disease which has been confirmed to be involved with abnormal or excessive body fat accumulation. There is still a lack of nationwide research in China to discuss the relationship between adiposity indicators included body mass index (BMI), waist circumference (WC), visceral adiposity index, waist-height ratio, waist-to-hip ratio (WHR) and diabetes. The question of which one is the best indicator of obesity to predict diabetes in China remains to be unclear.Data were collected from the China Health and Nutrition Survey (CHNS) in 2009, including 7,930 participants aged over 18 years old for cross-sectional analysis. Information about height, weight, WC, hip circumference, smoking status, alcohol consumption, physical activity, energy intake and blood samples were analyzed. Binary logistic regression models were used to explore the association of WC, BMI, WHR, waist-to-height ration (WHtR) and visceral adipose index (VAI) with the prevalence of diabetes in the 2009 CHNS respectively. Predictive potential of five adiposity indicators was validated by the area under the receiver operator characteristic curve (AUROC). The optimal cut-off points were determined by Youden's index, which was used to estimate the performance of adiposity indicators.The study shows patients in the highest quartile were more likely to have diabetes than those in the lowest quartile of WC (OR: 4.237, 95% CI: 3.265-5.499), BMI (OR: 3.312, 95% CI: 2.601-4.218), WHR (OR: 3.199, 95% CI: 2.493-4.104), WHtR (OR: 3.760, 95% CI: 2.891-4.890), VAI (OR: 4.347, 95% CI: 3.411-5.541). The area under the receiver operator characteristic curve of WC, BMI, WHR, WHtR and VAI for diabetes was 0.700, 0.663, 0.668, and 0.697 and 0.694, respectively. The optimal cut-offs regarding diabetes in Chinese are WHtR ≥0.520 for men and VAI ≥1.878 for women.Our findings indicate that WC, WHtR, BMI, WHR and VAI are all independent risk factors for diabetes among Chinese adults. WHtR is the most accurate indicator for diabetes in men, while VAI for women.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting 8%-13% of reproductive-aged women. The aetiology of the syndrome is complex, with genetic susceptibility, androgen exposure in early life and adiposity related dysfunction leading to perturbance in hypothalamic-ovarian function. PCOS clinical features are heterogeneous, with manifestations arising even in early adolescence, developing into multisystem reproductive, metabolic and psychological manifestations in adulthood. In this review, we will discuss challenges in the diagnosis of PCOS and understanding of the natural history of PCOS.

Excess dietary sucrose is associated with obesity and metabolic diseases. This relationship is driven by the malfunction of several cell types and tissues critical for the regulation of energy balance, including hypothalamic neurons and white adipose tissue (WAT). However, the mechanisms behind these effects of dietary sucrose are still unclear and might be independent of increased adiposity. Accumulating evidence has indicated that dysregulation of autophagy, a fundamental process for maintenance of cellular homeostasis, alters energy metabolism in hypothalamic neurons and WAT, but whether autophagy could mediate the detrimental effects of dietary sucrose on hypothalamic neurons and WAT that contribute to weight gain is a matter of debate. In this review, we examine the hypothesis that dysregulated autophagy in hypothalamic neurons and WAT is an adiposity-independent effect of sucrose that contributes to increased body weight gain. We propose that excess dietary sucrose leads to autophagy unbalance in hypothalamic neurons and WAT, which increases caloric intake and body weight, favoring the emergence of obesity and metabolic diseases.

Background Catch-up in weight-for-length in the first year of life results in more insulin resistance, an adverse lipid profile and more fat mass (FM) in 21-year-old adults born small for gestational age (SGA-CU) compared to peers born SGA without catch-up and those born appropriate for gestational age (AGA). The aim of present study was to investigate if the adverse metabolic health profile in the SGA-CU group would worsen or remain stable over the years and to determine the cardiometabolic health at 32 years between the SGA and AGA groups. Methods We longitudinally investigated 287 adults, 170 SGA with catch-up growth (SGA-CU) or persistent short stature (SGA-S) and 117 AGA at ages 21 and 32 years. Insulin sensitivity (Si) and β-cell function were measured by frequently sampled i.v. glucose tolerance test, body composition by dual-energy X-ray absorptiometry (DXA) scan, and abdominal adipose tissue and liver fat fraction by MRI scan. Also, fasting serum lipid levels and blood pressure were measured. Results At age 32 years, SGA-CU had lower Si than AGA (P = 0.030), while SGA-S had similar Si than AGA. FM and trunk fat were higher in SGA-CU than AGA (P = 0.033, P = 0.024, respectively), while SGA-S had lower lean body mass than SGA-CU and AGA (P = 0.001 and P < 0.001, respectively). SGA-CU had significantly higher levels of adverse lipids than AGA. Beta-cell function, visceral fat, liver fat fraction and blood pressure were similar in all groups. Metabolic health parameters in SGA-CU and SGA-S did not worsen compared to AGA during 11 years of follow-up. Gain in weight SDS from birth to age 32 years was associated with a higher risk of developing metabolic syndrome at age 32 years. Conclusion At age 32 years, SGA-CU adults had insulin resistance, higher FM with central adiposity and an adverse lipid profile. Postnatal catch-up growth increases the cardiometabolic risk; therefore, accelerated gain in weight should be prevented in SGA-born children.

Hypertension is the leading cause of overall mortality in low- and middle-income countries. In Brazil, there is paucity of data on the determinants of incident hypertension and related risk factors. We aimed to determine the incidence of hypertension in a sample from the Brazilian population and investigate possible relationships with body adiposity indexes. We assessed risk factors associated with cardiovascular disease, including adiposity body indexes and biochemical analysis, in a sample from the Baependi Heart Study before and after a 10-year follow-up. Hypertension was defined by the presence of systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or the use of antihypertensive drugs. From an initial sample of 1693 participants, 498 (56% women; mean age 38 ± 13 years) were eligible to be included. The overall hypertension incidence was 24.3% (22.3% in men and 25.6% in women). Persons who developed hypertension had higher prevalence of obesity, higher levels for blood pressure, higher frequency of dyslipidemia, and higher body adiposity indexes at baseline. The best prediction model for incident hypertension includes age, sex, HDL-c, SBP, and Body Mass Index (BMI) [AUC = 0.823, OR = 1.58 (95% CI 1.23-2.04)]. BMI was superior in its predictive capacity when compared to Body Adiposity Index (BAI), Body Roundness Index (BRI), and Visceral Adiposity Index (VAI). Incident hypertension in a sample from the Brazilian population was 24.3% after 10-year follow-up and BMI, albeit the simpler index to be calculated, is the best anthropometric index to predict incident hypertension.

Mechanisms linking a proinflammatory diet to obesity remain under investigation. The ability of diet to influence the gut microbiome (GM) in creating chronic low-grade systemic inflammation provides a plausible connection to adiposity.Assess whether any associations seen between the Energy-Adjusted Dietary Inflammatory Index (E-DII score), total fat mass, visceral adipose tissue (VAT), or liver fat (percentage volume) operated through the GM or microbial related inflammatory factors, in a multiethnic cross-sectional study.In the Multiethnic Cohort-Adiposity Phenotype Study (812 men, 843 women, aged 60-77 y) we tested whether associations between the E-DII and total adiposity, VAT, and liver fat function through the GM, LPS, and high-sensitivity C-reactive protein (hs-CRP). DXA-derived total fat mass, MRI-measured VAT, and MRI-based liver fat were measured. Participants provided stool and fasting blood samples and completed an FFQ. Stool bacterial DNA was amplified and the 16S rRNA gene was sequenced at the V1-V3 region. E-DII score was computed from FFQ data, with a higher E-DII representing a more proinflammatory diet. The associations between E-DII score, GM (10 phyla, 28 genera, α diversity), and adiposity phenotypes were examined using linear regression and mediation analyses, adjusting for confounders.There were positive total effects (c) between E-DII and total fat mass (c = 0.68; 95% CI: 0.47, 0.90), VAT (c = 4.61; 95% CI: 2.95, 6.27), and liver fat (c = 0.40; 95% CI: 0.27, 0.53). The association between E-DII score and total fat mass was mediated by LPS, Flavonifractor, [Ruminococcus] gnavus group, and Tyzzerella. The association between E-DII score and ectopic fat occurred indirectly through Fusobacteria, Christensenellaceae R-7 group, Coprococcus 2, Escherichia-Shigella, [Eubacterium] xylanophilum group, Flavonifractor, Lachnoclostridium, [Ruminococcus] gnavus group, Tyzzerella, [Ruminococcus] gnavus group (VAT only), and α diversity (liver fat only). There was no significant association between E-DII score and adiposity phenotype through hs-CRP.Associations found between E-DII and adiposity phenotypes occurred through the GM and LPS.

The obesity epidemic affects 40% of adults in the US, with approximately one-third of pregnant women classified as obese. Previous research suggests that children born to obese mothers are at increased risk for a number of health conditions. The mechanisms behind this increased risk are poorly understood. Increased exposure to in-utero inflammation induced by maternal obesity is proposed as an underlying mechanism for neurodevelopmental alterations in offspring. Utilizing a non-human primate model of maternal obesity, we hypothesized that maternal consumption of an obesogenic diet will predict offspring peripheral (e.g., cytokines and chemokines) and central (microglia number) inflammatory outcomes via the diet's effects on maternal adiposity and maternal inflammatory state during the third trimester. We used structural equation modeling to simultaneously examine the complex associations among maternal diet, metabolic state, adiposity, inflammation, and offspring central and peripheral inflammation. Four latent variables were created to capture maternal chemokines and pro-inflammatory cytokines, and offspring cytokine and chemokines. Model results showed that offspring microglia counts in the basolateral amygdala were associated with maternal diet (β = -0.622, p 0.01), adiposity (β = 0.593, p 0.01), and length of gestation (β = 0.164, p 0.05) but not with maternal chemokines (β = 0.135, p = 0.528) or maternal pro-inflammatory cytokines (β = 0.083, p = 0.683). Additionally, we found that juvenile offspring peripheral cytokines (β = -0.389, p 0.01) and chemokines (β = -0.298, p 0.05) were associated with a maternal adiposity-induced decrease in maternal circulating chemokines during the third trimester (β = -0.426, p 0.01). In summary, these data suggest that maternal diet and adiposity appear to directly predict offspring amygdala microglial counts while maternal adiposity influences offspring peripheral inflammatory outcomes via maternal inflammatory state.

Visceral adiposity index (VAI), an indicator of visceral fat, is associated with metabolic health and arterial stiffness. However, studies correlating VAI and stroke are limited. This study aimed to explore the association between VAI and incident stroke in the Chinese population.We retrospectively analysed the data of 9127 individuals enrolled in the China Health and Retirement Longitudinal Study. The first survey of the study was conducted during 2011-2012 and the individuals were followed up until Survey 4 (2017-2018). Multivariable-adjusted Cox regression models were used to evaluate the association between VAI and stroke. The mean age of the study population was 59.3 ± 9.5 years and 4938 (54.1%) participants were women. During the median follow-up of 5.2 [1.0-7.0] years, 833 (9.1%) participants developed stroke, and the cumulative incidence of stroke increased with increasing quartiles of VAI (8.6%, 8.7%, 9.2%, and 10.0%). Compared to those in the first quartile of VAI, individuals in the fourth quartile had an increased risk of stroke (adjusted hazard ratio, 1.45; 95% CI, 1.15-1.75). The results were stable in several sensitivity analyses.Our findings suggest a positive association between VAI and incident stroke in the Chinese population.

Objective: \ud To examine the association of changes in physical activity and adiposity with all-cause mortality and incident cardiovascular disease (CVD).\ud \ud Methods: \ud Physical activity, body mass index (BMI), body fat percentage, waist circumference, and waist to hip ratio changes were categorized on the basis of public health and clinical guidelines. Among 29,610 participants (mean ± SD follow-up, 5.1±2.1 years), 545 deaths and 2970 CVD events occurred. Participants were observed from baseline (March 13, 2006, to October 10, 2010) and follow-up (August 1, 2012 to November 9, 2018) assessment through March 31, 2021.\ud \ud Results: \ud Compared with stable-insufficient physical activity, increasing physical activity to meet guidelines at follow-up was associated with lower all-cause mortality (hazard ratio, 0.64 [0.49 to 0.85]) and CVD (0.83 [0.72 to 0.96]) risk. This risk was similar to that of those who achieved physical activity guidelines at both time points (all-cause mortality, 0.74 [0.60 to 0.92]; CVD, 0.88 [0.79 to 0.99]). For obese and overweight participants, decreasing BMI category was associated with a lower CVD risk (0.70 [0.47 to 1.04]) similar to the risk of those who had a healthy weight at both time points (0.85 [0.76 to 0.96]). In the joint analyses, the only combination that lowered all-cause mortality and CVD risk was physical activity increase and adiposity decrease over time (eg, CVD risk: BMI, 0.64 [0.42 to 0.96]; body fat percentage, 0.76 [0.55 to 0.97]; waist circumference, 0.66 [0.48 to 0.89]; waist to hip ratio, 0.78 [0.62 to 0.97]) compared with the reference group (stable physical activity and adiposity).\ud \ud Conclusion: \ud Increases in physical activity to meet guidelines lowered all-cause mortality and CVD risk equal to that of those who continually met guidelines. The risk was effectively eliminated in those who had concurrent adiposity decrease.