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This study aimed to assess the associations of total body fat and fat distribution with bone mineral density (BMD) among children and adolescents in this cross-sectional study. A total of 1032 boys and 897 girls aged 6–17 years were enrolled between May 2019 and June 2019 in Guangzhou, China. BMD, total body fat (fat mass index [FMI] and body fat percentage [BF%]), and fat distribution (trunk-to-limb and android-to-gynoid ratios) were measured by dual-energy X-ray absorptiometry. Inverse probability of treatment weighting regression was used to explore the association between fat and BMD. Traditional regression of covariate adjustment was applied as sensitivity analysis. Regression with inverse probability weighting suggested BF% and android-to-gynoid ratio were negatively associated with BMD in boys (β = − 0.12 and − 0.16, respectively; P < 0.05). Android-to-gynoid ratio was also inversely associated with BMD in girls (β = − 0.08, P < 0.05). When stratified by age, the negative associations were retained in boys aged 12–17 years (β = − 0.23 and − 0.25, respectively; P < 0.001). But for girls, it showed a positive association of FMI with BMD in the 6–9 years group (β = 0.33, P < 0.001) and a negative association between the android-to-gynoid ratio and BMD in the 10–17 years group (β = − 0.10, P < 0.05). Traditional regression supported the robustness of the results. Conclusion: Total body fat is positively associated with BMD in younger girls but inversely associated in older boys. As for abdominal adipose, it is associated with lower BMD in both older boys and girls. What is Known: • The lean mass has been consistently positively associated with bone mineral density (BMD) among children and adolescents. However, the impact of fat mass on BMD remained controversial. • Beyond total body fat, site-specific fat mass, especially abdominal adiposity, might impede bone formation. What is New: • The associations of total body fat and fat distribution with BMD in children and adolescents were gender- and age-specific. • More attention should be paid to the abdominal fat accumulation to promote bone health in older children. [ABSTRACT FROM AUTHOR]

Background: Central obesity is closely related to comorbidity, while the relationship between fat accumulation pattern and abnormal distribution in different parts of the central region of obese people and comorbidity is not clear. This study aimed to explore the relationship between fat distribution in central region and comorbidity among obese participants. Methods: We used observational data of NHANES 2011–2018 to identify 12 obesity-related comorbidities in 7 categories based on questionnaire responses from participants. Fat distribution is expressed by fat ratio, including Android, Gynoid, visceral, subcutaneous, visceral/subcutaneous (V/S), and total abdominal fat ratio. Logistic regression analysis were utilized to elucidate the association between fat distribution and comorbidity. Results: The comorbidity rate was about 54.1% among 4899 obese participants (weighted 60,180,984, 41.35 ± 11.16 years, 57.5% female). There were differences in fat distribution across the sexes and ages. Among men, Android fat ratio (OR, 4.21, 95% CI, 1.54–11.50, Ptrend=0.007), visceral fat ratio (OR, 2.16, 95% CI, 1.42– 3.29, Ptrend<0.001) and V/S (OR, 2.07, 95% CI, 1.43–2.99, Ptrend<0.001) were independent risk factors for comorbidity. Among these, there was a “J” shape correlation between Android fat ratio and comorbidity risk, while visceral fat ratio and V/S exhibited linear relationships with comorbidity risk. The Gynoid fat ratio (OR, 0.87, 95%CI, 0.80–0.95, Ptrend=0.001) and subcutaneous fat ratio (OR, 0.81, 95%CI, 0.67–0.98, Ptrend=0.016) both performed a protective role in the risk of comorbidity. In women, Android fat ratio (OR, 4.65, 95% CI, 2.11–10.24, Ptrend=0.020), visceral fat ratio (OR, 1.83, 95% CI, 1.31–2.56, Ptrend=0.001), and V/ S (OR, 1.80, 95% CI, 1.32–2.45, Ptrend=0.020) were also independent risk factors for comorbidity, with a dose-response relationship similar to that of men. Only the Gynoid fat ratio (OR, 0.93, 95% CI, 0.87–0.99, Ptrend=0.016) had a protective effect on female comorbidity. This association was also seen in obese participants of different age groups, comorbidity numbers, and comorbidity types, although it was more statistically significant in older, complex comorbidity, cardiovascular, cerebrovascular, and metabolic diseases. Conclusions: In the obese population, there were strong correlation between fat distribution in central region and comorbidity, which was affected by sex, age, number of comorbidities, and type of comorbidity. [ABSTRACT FROM AUTHOR]

Background: The onset of menarche is influenced by various factors, including genetic, morphological and socioeconomic factors. Objectives: The study aimed to examine the differences in adiposity levels and fat distribution between early, average, and late maturing girls from Kolkata, India. Sample and Methods: 936 Bengali girls included in a cross-sectional study were categorized as early, average or late maturing. The examination was school-based and conducted from 2005 to 2011. Six skinfolds (biceps, triceps, subscapular, suprailiac, abdominal and calf) were measured. Trunk-to-limbs, trunk-to-total, abdominal-to-trunk skinfold ratios, and total adiposity were calculated. Statistical differences between all menarche categories were assessed using Student t-test or Mann-Whitney test. Results: Early maturing girls were characterized by greater overall (% BF: early=24.3; average=24.0; late=23.8; p>0.05) and abdominal adiposity (as represented by skinfold thicknesses and values of studied indicators), compared to those with late or average age at menarche. Conclusions: Early menarche was associated with a tendency towards central adiposity and thus, increased risk of abdominal obesity. Future research should explore the association between the age at menarche and metabolic characteristics in ethnically diverse populations. Longitudinal studies and studies conducted on large cohorts are particularly valuable. It would be beneficial to adjust the results for factors such as diet or physical activity, as well as for ethnic characteristics in relation to the body's tissue composition.

Background & Aims: No prospective studies have examined the association between thigh subcutaneous fat distribution and non-alcoholic fatty liver disease (NAFLD). We investigated the associations of thigh subcutaneous fat distribution with incidence and remission of NAFLD in a community-based prospective cohort. Methods: We followed 1,787 subjects, who underwent abdominal ultrasonography, abdominal and femoral magnetic resonance imaging scans, and anthropometric assessments. Associations of thigh subcutaneous fat area/abdominal fat area ratio and thigh circumference/waist circumference ratio with incidence and remission of NAFLD were estimated using the modified Poisson regression model. Results: Over a mean 3.6-year follow-up, 239 incident cases of NAFLD and 207 regressed cases of NAFLD were identified. Increasing thigh subcutaneous fat area/abdominal fat area ratio was associated with a lower risk of incident NAFLD and a higher likelihood of remission of NAFLD [risk ratio (RR) per SD: 0.69, 95% CI 0.59-0.81; 1.20, 95% CI 1.07-1.34, respectively). Each one SD increase in thigh circumference/waist circumference ratio was associated with a 16% lower risk of incident NAFLD (RR 0.84, 95% CI 0.76-0.94) and a 22% higher likelihood of remission of NAFLD (RR 1.22, 95% CI 1.11-1.34). Additionally, the effects of thigh subcutaneous fat area/abdominal fat area ratio on the incidence and remission of NAFLD were mediated through adiponectin (14.9% and 26.6%), homeostasis model assessment of insulin resistance (9.5% and 23.9%), and triglyceride (7.5% and 19.1%). Conclusions: These results demonstrated that a favourable fat distribution, characterised by a greater ratio of thigh subcutaneous fat to abdominal fat, had a protective role against NAFLD. Impact and implications: The associations of thigh subcutaneous fat distribution with NAFLD incidence and remission have not been prospectively examined in a community-based cohort. Our findings suggest that greater thigh subcutaneous fat relative to a given amount of abdominal fat has a protective effect against NAFLD among the middle-aged and older Chinese populations.

BackgroundAdiposity has been previously associated with cognitive impairment and Alzheimer’s disease and related disorders (ADRD). Body mass index (BMI) is the most common measure of global adiposity, but inconsistent results were found since it is a global measurement. BMI does not represent regional fat distribution which differs between sexes, race, and age. Regional fat distribution may contribute differently to cognitive decline and Alzheimer’s disease (AD)-related brain changes. Fat-specific targeted therapies could lead to personalized improvement of cognition. The goal of this systematic review is to explore whether regional fat depots, rather than central obesity, should be used to understand the mechanism underlying the association between adiposity and brain.MethodsThis systematic review included 33 studies in the English language, conducted in humans aged 18 years and over with assessment of regional adiposity, cognitive function, dementia, and brain measures. We included only studies that have assessed regional adiposity using imaging technics and excluded studies that were review articles, abstract only or letters to editor. Studies on children and adolescents, animal studies, and studies of patients with gastrointestinal diseases were excluded. PubMed, PsychInfo and web of science were used as electronic databases for literature search until November 2022.ResultsBased on the currently available literature, the findings suggest that different regional fat depots are likely associated with increased risk of cognitive impairment, brain changes and dementia, especially AD. However, different regional fat depots can have different cognitive outcomes and affect the brain differently. Visceral adipose tissue (VAT) was the most studied regional fat, along with liver fat through non-alcoholic fatty liver disease (NAFLD). Pancreatic fat was the least studied regional fat.ConclusionRegional adiposity, which is modifiable, may explain discrepancies in associations of global adiposity, brain, and cognition. Specific regional fat depots lead to abnormal secretion of adipose factors which in turn may penetrate the blood brain barrier leading to brain damage and to cognitive decline.

Determining the mechanism driving body fat distribution will provide insights into obesity-related health risks. We used functional genomics tools to profile the epigenomic landscape to help infer the differential transcriptional potential of apple- and pear-shaped women’s subcutaneous adipose-derived stem cells (ADSCs). We found that CCCTC-binding factor (CTCF) expression and its chromatin binding were increased in ADSCs from pear donors compared to those from apple donors. Interestingly, the pear enriched CTCF binding sites were located predominantly at the active transcription start sites (TSSs) of genes with active histone marks and YY1 motifs and were also associated with pear enriched RNAPII binding. In contrast, apple enriched CTCF binding sites were mainly found at intergenic regions and when identified at TSS, they were enriched with the bivalent chromatin signatures. Altogether, we provide evidence that CTCF plays an important role in differential regulation of subcutaneous ADSCs gene expression and may influence the development of apple vs. pear body shape.

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the PEMT gene, including the waist–hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. PEMT expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, PEMT expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro Pemt knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in PEMT mRNA expression across the three studied tissues. Specifically, vis PEMT mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc PEMT expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT PEMT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of PEMT on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that PEMT plays a role in regulating FD and has implications in metabolic diseases.

ABSTRACT Aims/Introduction Glucagon‐like peptide‐1 receptor agonists (GLP‐1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP‐1Ras on fat distribution. Materials and Methods PubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP‐1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis. Results A total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP‐1Ras groups showed reductions in VAT (standard mean difference −0.54, 95% confidence interval [CI] −0.92, −0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference −0.44, 95% CI −0.60, −0.27, I2 = 44%, P

Abstract Objective To investigate the association between different body fat distribution and different sites of BMD in male and female populations. Methods Use the National Health and Nutrition Examination Survey (NHANES) datasets to select participants. The weighted linear regression model investigated the difference in body fat and Bone Mineral Density (BMD) in different gender. Multivariate adjusted smoothing curve-fitting and multiple linear regression models were used to explore whether an association existed between body fat distribution and BMD. Last, a subgroup analysis was performed according to age and gender group. Results Overall, 2881 participants were included in this study. Compared to males, female participants had lower BMD (P

Abstract Background Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. Methods Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses. Results Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr. Conclusions These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.

Simple Summary: Urothelial carcinoma is a highly aggressive cancer. In addition to the further development and innovation of therapeutic strategies, research into risk and prognostic factors plays a major role. Comparatively little is known about the physical constitution of patients and its impact on the prognosis of the disease. The aim of this retrospective study was to assess specific parameters of the body composition of patients undergoing nephroureterectomy due to urothelial carcinoma of the upper urinary tract, in addition to the usual criteria with regard to commonly used ones. Computed tomography-based measurements were used to determine muscle mass and fat distribution. The cohort included 142 patients. We were able to demonstrate that loss of skeletal muscle mass is a significant comorbidity-independent risk factor. Visceral fat, on the other hand, seems to be protective. In conclusion, specific parameters of body composition can contribute to patient-specific risk stratification. Radical nephroureterectomy (NUE) is the gold standard treatment for high-risk urothelial cancer of the upper urinary tract (UTUC). Besides sarcopenia and frailty, fat distribution is moving increasingly into focus. Components of body composition were assessed in patients undergoing NUE due to UTUC. The study cohort included 142 patients. By using CT-based measurements, the skeletal muscle index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured at the height of the third lumbar vertebra. Overall survival (OS) and cancer-specific survival (CSS) were estimated using univariable und multivariable Cox regression models. The prevalence of sarcopenia in the study population (n = 142) was 37%. OS and CSS were significantly reduced in sarcopenic patients. In the multivariable cox regression analysis, including age, ACE-27, T-stage, R-stage, LVI and necrosis, sarcopenia remained a significant risk factor of OS (HR, 1.77; 95% CI 1.02–3.07; p = 0.042) and CSS (HR, 2.17; 95% CI 1.18–3.99; p = 0.012). High visceral adipose tissue seems to be protective, although not statistically significant. Sarcopenia is a comorbidity-independent risk factor in patients who underwent NUE due to UTUC. Visceral fat represents a potentially protective factor. These results suggest that specific factors of body composition can be used for better risk stratification. [ABSTRACT FROM AUTHOR]

Obesity and upper-body fat distribution are independent, cardiometabolic risk factors but whether they also display comparable associations with cancer risk is unknown. We investigated the causal relationships between body mass index (BMI) and BMI-adjusted waist-to-hip ratio (WHRadjBMI) and cancer risk and searched for potential drivers linking these traits to carcinogenesis using two-sample and multivariable Mendelian randomisation. In women, genetically instrumented higher BMI was associated with lower breast (OR = 0.87, 95% CI 0.81–0.93) and higher endometrial (OR = 1.75, 95% CI 1.55–1.96) cancer risk whilst WHRadjBMI was associated with higher colon cancer risk (OR = 1.22, 95% CI 1.07–1.42). In men, elevated BMI was associated with lower prostate cancer risk (OR = 0.91, 95% CI 0.85–0.98). Mechanistically, testosterone and insulin mediated 21% and 35%, respectively of the total, genetically determined association of BMI with endometrial cancer risk whilst HDL cholesterol and IGF-1 mediated 40% and 22%, respectively of the association between BMI and breast cancer risk. In men, testosterone mediated 21% of the association between BMI and prostate cancer risk. Colon cancer aside, the total amount of body fat might be more important than its location in modulating cancer susceptibility due to differential effects of obesity and fat distribution on adiposity-associated cancer drivers. [ABSTRACT FROM AUTHOR]

Human voice is an extremely important biological signal which contains information about sex, age, emotional state, health and physical features of a speaker. Estimating a physical appearance from a vocal cue can be an important asset for sciences including forensics and dietetics. Although there have been several studies focused on the relationships between vocal parameters and ratings of height, weight, age and musculature of a speaker, to our knowledge, there has not been a study examining the assessment of one's BMI based on voice alone. The purpose of the current study was to determine the ability of female "Judges" to evaluate speakers' (men and women) obesity and body fat distribution from their vocal cues. It has also been checked which voice parameters are key vocal cues in this assessment. The study material consisted of 12 adult speakers' (6 women) voice recordings assessed by 87 "Judges" based on a 5-point graphic scale presenting body fat level and distribution (separately for men and women). For each speaker body height, weight, BMI, Visceral Fat Level (VFL, InBody 270) and acoustic parameters were measured. In addition, the accuracy of BMI category was verified. This study also aimed to determine which vocal parameters were cues for the assessment for men and women. To achieve it, two independent experiments were conducted: I: "Judges" had to choose one (obese) speaker from 3 voices (in 4 series); II: they were asked to rate body fat level of the same 12 speakers based on 5-point graphic scale. Obese speakers (i.e., BMI above 30) were selected correctly with the accuracy greater than predicted by chance (experiment I). By using a graphic scale, our study found that speakers exhibiting higher BMI were rated as fatter (experiment II). For male speakers the most important vocal predictors of the BMI were harmonics-to-noise ratio (HNR) and formant dispersion (Df); for women: formant spacing (Pf) and intensity (loudness). Human voice contains information about one's increased BMI level which are hidden in some vocal cues. [ABSTRACT FROM AUTHOR]

Background & Aims: Non‐alcoholic fatty liver disease (NAFLD) is a heterogeneous disorder, but the factors that determine this heterogeneity remain poorly understood. Adipose tissue dysfunction is causally linked to NAFLD since it causes intrahepatic triglyceride (IHTG) accumulation through increased hepatic lipid flow, due to insulin resistance and pro‐inflammatory adipokines release. While many studies in NAFLD have looked at total adiposity (i.e. mainly subcutaneous fat, SC‐AT), it is still unclear the possible impact of visceral fat (VF). Thus, we investigated how VF versus SC‐AT was related to NAFLD severity in lean, overweight and obese individuals versus lean controls. Methods: Thirty‐two non‐diabetic NAFLD with liver biopsy (BMI 21.4–34.7 kg/m2) and eight lean individuals (BMI 19.6–22.8 kg/m2) were characterized for fat distribution (VF, SC‐AT and IHTG by magnetic resonance imaging), lipolysis and insulin resistance by tracer infusion, free fatty acids (FFAs) and triglyceride (TAG) concentration and composition (by mass spectrometry). Results: Intrahepatic triglyceride was positively associated with lipolysis, adipose tissue insulin resistance (Adipo‐IR), TAG concentrations, and increased saturated/unsaturated FFA ratio. Compared to controls VF was higher in NAFLD (including lean individuals), increased with fibrosis stage and associated with insulin resistance in liver, muscle and adipose tissue, increased lipolysis and decreased adiponectin levels. Collectively, our results suggest that VF accumulation, given its location close to the liver, is one of the major risk factors for NAFLD. Conclusions: These findings propose VF as an early indicator of NAFLD progression independently of BMI, which may allow for evidence‐based prevention and intervention strategies. [ABSTRACT FROM AUTHOR]

Abstract Background and objectives Disorders of adipose tissue distribution in people living with the human immunodeficiency virus (HIV) have been associated with significant metabolic derangements that increase their risk of cardiometabolic and other chronic diseases. Systematic reviews focusing on supervised laboratory-based exercise interventions demonstrate that these interventions improve adipose tissue distribution and related health outcomes in people living with HIV (PLWH). However, there is a need to examine the effectiveness of more pragmatic home or community exercise programmes. The aim of this review will be to synthesize existing evidence on the effectiveness of self-managed home or community exercise interventions to improve physical activity levels, adipose tissue distribution and associated health indices in PLWH. Methods This review will encompass interventional studies that evaluate the effect of prescribed exercise programmes performed in the home or community with minimal supervision, by adults living with HIV. The following will be searched from inception: PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database, SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Clinicaltrials.gov. Screening of studies and data extraction will be conducted by two independent reviewers. The risk of bias in included studies will be assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the Risk of Bias In Non-Randomized Studies-of Interventions (ROBINS-I) tool for non-randomized concurrently controlled and single-arm interventional studies. A random effects meta-analysis will be used to pool effect estimates for outcomes of interest (measures of physical activity and body adiposity). However, if pooling is deemed inappropriate due to substantial differences between studies, a narrative synthesis will be performed. This protocol is written according to the Preferred Reporting Items for Systematic reviews and Meta-analysis Protocols 2015 statement (see Additional file 1). Discussion This review shall provide evidence to support or disapprove the prescription of self-managed exercise interventions in a particularly vulnerable population. We will equally explore the potential impact of technology in improving physical activity outcomes. Our findings could help guide clinicians involved in the care of PLWH in prescribing exercise and inform the design of future trials and research. Systematic review registration PROSPERO CRD42021223357 .

Abstract Background The comorbidity between polycystic ovary syndrome (PCOS) and obesity has long been observed in clinical settings, but their shared genetic basis remains unclear. Methods Leveraging summary statistics of large-scale GWAS(s) conducted in European-ancestry populations on body mass index (adult BMI, N female=434,794; childhood BMI, N=39,620), waist-to-hip ratio (WHR, N female=381,152), WHR adjusted for BMI (WHRadjBMI, N female=379,501), and PCOS (N case=10,074, N control=103,164), we performed a large-scale genome-wide cross-trait analysis to quantify overall and local genetic correlation, to identify shared loci, and to infer causal relationship. Results We found positive genetic correlations between PCOS and adult BMI (r g =0.47, P=2.19×10−16), childhood BMI (r g =0.31, P=6.72×10−5), and WHR (r g =0.32, P=1.34×10−10), all withstanding Bonferroni correction. A suggestive significant genetic correlation was found between PCOS and WHRadjBMI (r g =0.09, P=0.04). Partitioning the whole genome into 1703 nearly independent regions, we observed a significant local genetic correlation for adult BMI and PCOS at chromosome 18: 57630483–59020751. We identified 16 shared loci underlying PCOS and obesity-related traits via cross-trait meta-analysis including 9 loci shared between BMI and PCOS (adult BMI and PCOS: 5 loci; childhood BMI and PCOS: 4 loci), 6 loci shared between WHR and PCOS, and 5 loci shared between WHRadjBMI and PCOS. Mendelian randomization (MR) supported the causal roles of both adult BMI (OR=2.92, 95% CI=2.33–3.67) and childhood BMI (OR=2.76, 95% CI=2.09–3.66) in PCOS, but not WHR (OR=1.19, 95% CI=0.93–1.52) or WHRadjBMI (OR=1.03, 95% CI=0.87–1.22). Genetic predisposition to PCOS did not seem to influence the risk of obesity-related traits. Conclusions Our cross-trait analysis suggests a shared genetic basis underlying obesity and PCOS and provides novel insights into the biological mechanisms underlying these complex traits. Our work informs public health intervention by confirming the important role of weight management in PCOS prevention.

Abstract Background Body composition alterations may participate in the pathophysiological processes of type 2 diabetes (T2D). A sedentary lifestyle may be responsible for alterations of body composition and adverse consequences, but on which body composition of patients with T2D and to what extent the sedentary lifestyle has an effect have been poorly investigated. Methods We recruited 402 patients with T2D for this cross-sectional study. All patients received questionnaires to evaluate sedentary time and were further divided into three subgroups: low sedentary time (LST, 8 h, n = 164). Each patient underwent a dual energy X-ray absorptiometry (DXA) scan to detect body composition, which included body fat percentage (B-FAT), trunk fat percentage (T-FAT), appendicular skeletal muscle index (ASMI), lumbar spine bone mineral density (BMD) (LS-BMD), femoral neck BMD (FN-BMD), hip BMD (H-BMD) and total BMD (T-BMD). Other relevant clinical data were also collected. Results With increasing sedentary time (from the LST to HST group), B-FAT and T-FAT were notably increased, while ASMI, LS-BMD, FN-BMD, H-BMD and T-BMD were decreased (p for trend

Abstract Background It has been reported that dietary fats and genetic factors in individuals are associated with the pattern of fat distribution. This study aimed to evaluate the interaction between dietary fats intake and Caveolin1 (CAV-1) rs 3807s992 polymorphism with fat distribution in overweight and obese women. Methods A total of 221 participants were included in the current cross-sectional study. Body composition, biochemical parameters were evaluated by body composition analyzer and Pars Azmoon kits and genotypes determination was performed by PCR–RFLP, dietary fats were measured using a validated semi-quantitative food frequency questionnaire (FAQ). Results The frequency of GG, AA and AG genotypes were 53.1, 24.6, and 22.3%, respectively, and the mean intake of total dietary fat intake was 97.47 ± 36.87 g. There was positive significant interaction between total fat intake and AA genotype on visceral fat level (p = 0.001), trunk fat (p = 0.01) and waist circumference (p = 0.05), positive significant interaction between total fat intake and AG genotype on the waist to hip ratio (WHR) (p = 0.02) and visceral fat level (p = 0.05), positive borderline significant interaction between saturated fatty acid and AA genotype on the trunk fat (p = 0.06), and between trans-fatty acids and AG genotype on WHR (p = 0.04), visceral fat level (p = 0.01), and between monounsaturated fatty acid and AG genotype on WHR (p = 0.04), and a borderline interaction between polyunsaturated fatty acid and AA genotypes on visceral fat level (p = 0.06), negative significant interaction between AG genotypes and linolenic acid on WHR (p = 0.04), borderline significant interaction between ALA and AG genotype on WHR (p = 0.06). Conclusions Our findings showed that CAV-1 rs 3807992 polymorphism and dietary fats were associated with fat distributions in individuals.

Objective: The observational studies indicate an association between obesity and epilepsy, but it is unclear whether such an association responds to causality. The objective of this study was to determine the causal relationship between obesity and fat distribution and epilepsy subtypes based on waist circumference, hip circumference (HP), waist-hip ratio (WHR), and body mass index (BMI). Methods: A two-sample Mendelian randomization study was conducted separately for the four indicators of obesity and epilepsy and its seven subtypes, with reverse Mendelian randomization and multivariate Mendelian randomization for significant outcomes. Results: A two-sample Mendelian randomized analysis informed us that waist circumference was a risk factor for juvenilemyoclonic epilepsy (beta = 0.0299, P = 4.60 × 10-3). The increase in hip circumference increased the risk of juvenile myoclonic epilepsy and epilepsy, with effect values of 0.0283 (P = 2.01 × 10-3) and 0.0928 (P = 1.40 × 10-2), respectively. Furthermore, children with a higher BMI exhibit a higher risk of epilepsy (beta = 0.0148 P = 1.05 × 10-3). The reverse Mendelian randomization study revealed that childhood absence epilepsy increased its BMI (beta = 0.8980, P = 7.52 × 10-7), and juvenile myoclonic epilepsy increased its waist circumference (beta = 0.7322, P = 3.26 × 10-2). Multivariate Mendelian randomization revealed that an increase in hip circumference and waist-hip ratio increased the risk of juvenile myoclonic epilepsy, with an effect value of 0.1051 (P = 9.75 × 10-4) and 0.1430 (P = 3.99 × 10-3), respectively, while an increase in BMI and waist circumference instead decreased their risk, with effect values of -0.0951 (P = 3.14×10-2) and-0.0541 (P=1.71×10-2). In contrast, multivariateMendelian randomization for childhood absence epilepsy and epilepsy did not identify any independent risk factors. Significance: Our findings provide novel evidence in favor of obesity as a risk factor for epilepsy and waist circumference as a risk factor for juvenile myoclonic epilepsy. Increased hip circumference confers an elevated risk of juvenile myoclonic epilepsy and epilepsy (all documented cases), and a high BMI increases the risk of childhood absence epilepsy. With this, new insights are provided into the energy metabolism of epilepsy, which supports further nutritional interventions and the search for new therapeutic targets. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the relationship between the proportion of Android to Gynoid ratio and the incidence of kidney stones among US adults. Methods: Participants aged 20-59 years from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database were selected to assess the association between Android to Gynoid ratio and kidney stone prevalence using logistic regression analysis, subgroup analysis and calculation of doseresponse curves. Results: This study ultimately included 10858 participants, of whom 859 selfreported a history of kidney stones. And after adjusting for all confounders, an increased Android to Gynoid ratiowas associated with an increased prevalence of kidney stones (OR=2.75, 95% CI:1.62-4.88). And subgroup analysis showed an increased prevalence of kidney stones in women (OR=3.55, 95% CI: 1.54-8.22), non-diabetic (OR=2.59, 95% CI: 1.45-4.60), 60 > age = 40 years (OR=3.51, 95% CI: 1.83-6.71), Mexican-American (OR=4.35, 95% CI: 1.40-13.53) and white (OR=3.86, 95% CI: 1.82-8.18) groups, there was a significant positive association between A/G ratio and kidney stones. In contrast, in the hypertensive subgroup, the A/G ratio was associated with kidney stones in all groups. Conclusions: Higher Android to Gynoid ratio is associated with a high prevalence of kidney stone disease. [ABSTRACT FROM AUTHOR]

Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma. We sought to endotype childhood obesity–related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. Multiomics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and T H -cell transcriptome and DNA methylome data sets. Two clusters (n = 28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio [WHR], and body mass index [BMI] z score), metabolic, nutrient, and T H -cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different data set combinations. Metabolic measures attenuated the association of neck, WHR, and BMI z score with FEV 1 /forced vital capacity (FVC) ratio and expiratory reserve volume (ERV), of neck, midarm, and BMI z score with functional residual capacity, but only of WHR with inspiratory capacity. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z score with functional residual capacity, and of WHR with FEV 1 /FVC ratio, ERV, and inspiratory capacity. T H -cell transcriptome attenuated the association of all 4 anthropometric measures with FEV 1 /FVC ratio, but only of WHR with ERV and inspiratory capacity. The DNA methylome attenuated the association of all 4 anthropometric measures with FEV 1 /FVC ratio and ERV, but only of WHR with inspiratory capacity. Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity–related asthma. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Online Turkish Journal of Health Sciences (OTJHS) / Online Türk Sağlık Bilimleri Dergisi is the property of Oguz KARABAY and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Eating speed has been reported to be associated with energy intake, body weight, waist circumference (WC), and total body fat. However, no study has explored the association between eating speed and body fat distribution, especially its difference among different age or body mass index (BMI) groups. Methods: 4770 participants aged 18–80 years were recruited from the baseline survey of the Lanxi Cohort Study. They were categorized into three groups according to meal duration. Linear regression analyses were performed among all participants and separately by age group and obesity status to evaluate the associations of WC and total and regional fat mass percentages (FM%) with eating speed. Results: After adjusting for confounding factors, eating slowly was significantly related to lower WC, lower total, trunk, and android FM%, lower android-to-gynoid fat mass ratio, and higher leg and gynoid FM%. After stratification by age or obesity status, the associations were especially prominent among participants aged 18–44 years or those with BMI < 24 kg/m2. No significant trends were found for participants aged 65–80 years or those who were overweight/obese. Conclusions: Eating slowly is closely related with better fat distribution among Chinese adults, especially for those aged 18–44 years and those with BMI < 24 kg/m2. If confirmed prospectively, it might be a potential efficient approach to improve fat distribution. [ABSTRACT FROM AUTHOR]

Background: Increased waist-to-hip ratio (WHR) is associated with increased mortality and risk of type 2 diabetes and cardiovascular disease. The TBX15-WARS2 locus has consistently been associated with increased WHR. Previous study of the hypomorphic Wars2V117L/V117L mouse model found phenotypes including severely reduced fat mass, and white adipose tissue (WAT) browning, suggesting Wars2 could be a potential modulator of fat distribution and WAT browning. Methods: To test for differences in browning induction across different adipose depots of Wars2V117L/V117L mice, we measured multiple browning markers of a 4-month old chow-fed cohort in subcutaneous and visceral WAT and brown adipose tissue (BAT). To explain previously observed fat mass loss, we also tested for the upregulation of plasma mitokines FGF21 and GDF15 and for differences in food intake in the same cohort. Finally, to test for diet-associated differences in fat distribution, we placed Wars2V117L/V117L mice on low-fat or highfat diet (LFD, HFD) and assessed their body composition by Echo-MRI and compared terminal adipose depot weights at 6 months of age. Results: The chow-fed Wars2V117L/V117L mice showedmore changes inWAT browning marker gene expression in the subcutaneous inguinal WAT depot (iWAT) than in the visceral gonadal WAT depot (gWAT). These mice also demonstrated reduced food intake and elevated plasma FGF21 and GDF15, and mRNA from heart and BAT. When exposed to HFD, the Wars2V117L/V117L mice showed resistance to diet-induced obesity and a male and HFD-specific reduction of gWAT: iWAT ratio. Conclusion: Severe reduction of Wars2 gene function causes a systemic phenotype which leads to upregulation of FGF21 and GDF15, resulting in reduced food intake and depot-specific changes in browning and fat mass. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that at a similar body mass index, Middle Eastern immigrants are more insulin resistant and at higher risk for type 2 diabetes (T2D) than native Europeans. Insulin resistance is strongly associated with disturbed fat metabolism and cardiovascular disease (CVD). However, fat metabolism is poorly investigated comparing Middle Eastern and European ethnicities. Methods: This observational study included 26 Iraqi and 16 Swedish-born men without T2D or clinical risk factors for CVD. An oral fat tolerance test (OFTT) was performed, where plasma triglycerides (p-TG) were measured for 6 h. mRNA expression and adipocyte size were measured in subcutaneous adipose tissue biopsies collected prior to OFTT, and magnetic resonance imaging was conducted to assess body fat distribution. Results: The median p-TG accumulation was higher and the clearance slower among Iraqis than Swedes. None of the groups reached their fasting p-TG (Iraqis 1.55 mmol/l; Swedes 0.95 mmol/l) after 6 h (Iraqis p-TG 3.10 mmol/l; Swedes p-TG 1.50 mmol/l). Adipocyte size, mRNA expression, and fat accumulation in the liver, muscle and abdomen were similar in both groups. Conclusion: Postprandial p-TG levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants without CVD risk factors. [ABSTRACT FROM AUTHOR]

Aim: Perirenal fat (PRF) is an independent predictor for chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) patients. Previous studies speculated that PRF may promote renal dysfunction through affecting renal hemodynamics. To verify this hypothesis, we studied the relationship between PRF and renal hemodynamics in T2DM., Methods: 91 T2DM patients were included. PRF thickness (PRFT) was measured by magnetic resonance imaging. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by renal dynamic imaging. Renal vascular resistance (RVR), glomerular hydrostatic pressure (P GLO ), afferent (R A ) and efferent (R E ) arteriolar resistance were calculated by Gomez equations. Multiple linear regression was used to determine the relationship between PRFT and renal hemodynamics. Mediation analysis was conducted to estimate the mediation effects of renal hemodynamics on the relationship between PRF and CKD., Results: All patients were divided into three groups according to the tertiles of PRFT. Compared with patients in tertile 1, GFR and ERPF were significantly decreased in patients in tertile 3, while RVR and R A were significantly increased. PRFT was negatively correlated with GFR, ERPF and P GLO , and positively correlated with RVR and R A after adjustment for sex, age, visceral adipose tissue and treatments with ACE inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter protein-2 inhibitors. Moreover, RVR and R A mediated the effect of PRF on GFR, with a mediated proportion of 29.1% and 41.4% respectively., Conclusion: In T2DM patients, PRF was negatively correlated with GFR, and positively correlated with R A . R A mediated the relationship between PRF and CKD., 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. Published by Elsevier Masson SAS.)

Background: Cardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life., Methods: We followed 364,240 participants from UK Biobank aged 40-73 years from 2006 - 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders., Results: During a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction <0.001), and increase with polygenic risk for cardiovascular disease (P for interaction <0.001). Consistently, breastfeeding in infancy was associated with cardiovascular disease risk factors including lower body mass index 0.92 (95% CI: 0.89, 0.95), body fat percentage 0.85 (95% CI: 0.83, 0.87), android to gynoid fat ratio 0.89 (95% CI: 0.83, 0.96), visceral adipose tissue 0.92 (95% CI: 0.84, 1.01), as well as lower C-reactive protein level 0.95 (95% CI: 0.94, 0.97) and a lower risk of metabolic syndrome 0.89 (95% CI: 0.85, 0.92)., Conclusions: Breastfeeding in infancy was associated with a lower risk of cardiovascular disease in middle-aged and older adulthood. Promoting breastfeeding is vital not only for promoting child health, but also for halting the increasing trend of cardiovascular disease in adults., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Heterogenous deposition and homeostasis roles of physiologic and ectopic adipose tissues underscore the impact of fat compartmentalization on cardiometabolic risk. We aimed to characterize the distribution of abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT), and liver fat on magnetic resonance imaging (MRI), and evaluate their associations with anthropometric indices and adverse cardiac remodeling., Methods: In this cross-sectional observational study, 149 Asian adults (57.0 ± 12.8 years; 65% males) with at least one cardiometabolic risk factor underwent multiparametric fat and cardiovascular MRI. Anthropometric indices included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and bioimpedance body fat mass (BFM). Associations between fat depots and anthropometric measures as well as cardiac remodeling features were examined as a single cohort and stratified by type 2 diabetes mellitus (T2DM) status., Results: VAT and SAT had opposing associations with liver fat and EAT. Therefore the VAT/SAT ratio was explored as an integrated marker of visceral adiposity. VAT/SAT was positively associated with EAT (β=0.35, P<0.001) and liver fat (β=0.32, P=0.003) independent of confounders. Of the anthropometric measurements assessed, only WHR was independently associated with VAT/SAT (β=0.17, P=0.021). Individuals with T2DM had higher VAT and lower SAT compared to those without T2DM, translating to a significantly higher VAT/SAT ratio. EAT volume was independently associated with adverse features of cardiac remodeling: increased left ventricular (LV) mass (β=0.24, P=0.005), larger myocyte volume (β=0.26, P=0.001), increased myocardial fibrosis (β=0.19, P=0.023), higher concentricity (β=0.18, P=0.035), and elevated wall stress (β=-0.18, P=0.023)., Conclusion: Multiparametric MRI revealed abdominal VAT and SAT have differential associations with anthropometric indices and ectopic fats in a single cohort of Asians at risk of cardiometabolic disease. People with T2DM have expanded VAT and diminished SAT, endorsing the VAT/SAT ratio beyond usual anthropometric measurements as a marker for multiorgan visceral fat composition. Among the fat depots examined, EAT is uniquely associated with adverse cardiac remodeling, suggesting its distinctive cardiometabolic properties and implications., 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 Lee, Han, Toh, Bryant, Boubertakh, Le and Chin.)

Background: Increased waist-to-hip ratio (WHR) is associated with increased mortality and risk of type 2 diabetes and cardiovascular disease. The TBX15-WARS2 locus has consistently been associated with increased WHR. Previous study of the hypomorphic Wars2V117L/V117L mouse model found phenotypes including severely reduced fat mass, and white adipose tissue (WAT) browning, suggesting Wars2 could be a potential modulator of fat distribution and WAT browning.Methods: To test for differences in browning induction across different adipose depots of Wars2V117L/V117L mice, we measured multiple browning markers of a 4-month old chow-fed cohort in subcutaneous and visceral WAT and brown adipose tissue (BAT). To explain previously observed fat mass loss, we also tested for the upregulation of plasma mitokines FGF21 and GDF15 and for differences in food intake in the same cohort. Finally, to test for diet-associated differences in fat distribution, we placed Wars2V117L/V117L mice on low-fat or high-fat diet (LFD, HFD) and assessed their body composition by Echo-MRI and compared terminal adipose depot weights at 6 months of age.Results: The chow-fed Wars2V117L/V117L mice showed more changes in WAT browning marker gene expression in the subcutaneous inguinal WAT depot (iWAT) than in the visceral gonadal WAT depot (gWAT). These mice also demonstrated reduced food intake and elevated plasma FGF21 and GDF15, and mRNA from heart and BAT. When exposed to HFD, the Wars2V117L/V117L mice showed resistance to diet-induced obesity and a male and HFD-specific reduction of gWAT: iWAT ratio.Conclusion: Severe reduction of Wars2 gene function causes a systemic phenotype which leads to upregulation of FGF21 and GDF15, resulting in reduced food intake and depot-specific changes in browning and fat mass.

Knee osteoarthritis (KOA) is one of the most common joint diseases, especially in individuals with obesity. Another condition within this population, and which presents frequently, is sarcopenic obesity (SO), defined as an increase in body fat and a decrease in muscle mass and strength. The current paper aims to describe recent nutritional strategies which can generally improve KOA clinical severity and, at the same time, ameliorate SO indices. Searches were carried out in the PubMed and Science Direct databases and data were summarized using a narrative approach. Certain key findings have been revealed. Firstly, the screening and identification of SO in patients with KOA is important, and to this end, simple physical performance tests and anthropometric measures are available in the literature. Secondly, adherence to a Mediterranean diet and the achievement of significant body weight loss by means of low-calorie diets (LCDs) remain the cornerstone nutritional treatment in this population. Thirdly, supplementation with certain micronutrients such as vitamin D, essential and non-essential amino acids, as well as whey protein, also appear to be beneficial. In conclusion, in the current review, we presented a detailed flowchart of three different nutritional tracks that can be adopted to improve both KOA and SO based on joint disease clinical severity.

Objective: To investigate the association between different body fat distribution and different sites of BMD in male and female populations. Methods: Use the National Health and Nutrition Examination Survey (NHANES) datasets to select participants. The weighted linear regression model investigated the difference in body fat and Bone Mineral Density (BMD) in different gender. Multivariate adjusted smoothing curve-fitting and multiple linear regression models were used to explore whether an association existed between body fat distribution and BMD. Last, a subgroup analysis was performed according to age and gender group. Results: Overall, 2881 participants were included in this study. Compared to males, female participants had lower BMD (P < 0.05) and higher Gynoid fat mass (P < 0.00001), while there was no difference between Android fat mass (P = 0.91). Android fat mass was positively associated with Total femur BMD (Males, β = 0.044, 95% CI = 0.037, 0.051, P < 0.00001; Females, β = 0.044, 95% CI = 0.039, 0.049, P < 0.00001), Femoral neck BMD (Males, β = 0.034, 95% CI = 0.027, 0.041, P < 0.00001; Females, β = 0.032, 95% CI = 0.027, 0.037, P < 0.00001), and Total spine BMD (Males, β = 0.036, 95% CI = 0.029, 0.044, P < 0.00001; Females, β = 0.025, 95% CI = 0.019, 0.031, P < 0.00001). The Gynoid fat mass, subgroup analysis of age and ethnicity reached similar results. Conclusion: Body fat in different regions was positively associated with BMD in different sites, and this association persisted in subgroup analyses across age and race in different gender. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Glucagon‐like peptide‐1 receptor agonists (GLP‐1Ras) are widely used to treat type 2 diabetes. They not only reduce glucose, but also have a positive effect on weight loss. However, few studies have reported the effect of GLP‐1Ras on fat distribution. Materials and Methods: PubMed, Cochrane, Embase and ClinicalTrials.gov were searched for randomized controlled trials on GLP‐1Ras and type 2 diabetes, published from inception to June 2021. Our main outcomes were the reductions of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Other anthropometric outcomes were also assessed. We used the Cochrane Collaboration tools to assess the risk of bias in the included studies. The quality of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation profiler version 3.6. Review Manager 5.4.1 and Stata 16.0 were used for data analysis. Results: A total of 10 studies involving 541 patients were included. Compared with the control groups, the GLP‐1Ras groups showed reductions in VAT (standard mean difference −0.54, 95% confidence interval [CI] −0.92, −0.17, I2 = 79%, P = 0.005) and SAT (standard mean difference −0.44, 95% CI −0.60, −0.27, I2 = 44%, P < 0.00001). In addition, bodyweight (weighted mean difference −3.59, 95% CI −4.30, −2.88, I2 = 0%, P < 0.00001), waist circumference (weighted mean difference −3.09, 95% CI −4.66, −1.52, I2 = 70%, P = 0.0001) and body mass index (weighted mean difference −1.11, 95% CI −1.35, −0.86, I2 = 47%, P < 0.00001) were significantly decreased. According to the Grades of Recommendation, Assessment, Development and Evaluation approach, the level of evidence was low or moderate. Conclusion: This study highlights that GLP‐1Ras, especially liraglutide and exenatide, might play an active role in fat distribution in patients with type 2 diabetes. After treatment with GLP‐1Ras, both VAT and SAT decreased, and the decrease of VAT was numerically greater than that of SAT. [ABSTRACT FROM AUTHOR]

• The fat distribution in children with CP seems to be gynoid distributed. • The FMI in children with CP seems to be under average. To evaluate the body fat distribution in children with cerebral palsy (CP). The present study focusses on a monocentric retrospective analysis of body fat distribution from children diagnosed with CP. The children participated in a rehabilitation program. Reference centiles were calculated based on data from the National Health and Nutrition Examination Survey (NHANES, 1999–2004). Z-scores for trunk-to-leg fat ratio were calculated. Further, fat mass index (FMI) was evaluated based on percentiles that have already been published. 237 males and 194 females with CP were considered (mean age: 11 years and 11 months [SD 3 years]). These were compared to 1059 males and 796 females from the NHANES (mean age: 14 years and 7 months [SD 3 years and 4 months]). The z-scores for trunk-to-leg fat ratio showed the following values: mean –0.47 (SD 1.50) for males, –0.49 (SD 1.11), for females, –0.48 (SD 1.34) for all. The z-scores for FMI showed the following values: mean –0.29 (SD 0.70) for males, –0.88 (SD 2.0) for females, –0.55 (SD 1.46) for all. The results showed rather a gynoid fat distribution and a lower FMI in children with CP than in the reference population (NHANES 1999–2004). [ABSTRACT FROM AUTHOR]

Background: Urinary stones usually start at a young age and tend to recur. Therefore, preventing stone occurrence and recurrence in young people is crucial. We aimed to investigate the association between subcutaneous adipose tissue, visceral adipose tissue, and stone episodes in young people. Methods: We retrospectively studied patients aged below 40 years with kidney or ureteral stones. Data on demographic and metabolic characteristics, urolithiasis history, subcutaneous fat area (SFA), and visceral fat area (VFA) were collected. We evaluated the association between SFA or VFA and the occurrence or recurrence of stone episodes using binary logistic regression and Poisson regression analyses. Results: In total, 120 patients were included. Abdominal obesity, overweight or obesity, dyslipidemia, metabolic syndrome, SFA, and VFA increased with the number of stone episodes (all p < 0.05). The increase in SFA was independently associated with episode occurrence (p = 0.015). Patients with an SFA > 97 cm2 had a higher risk of episode occurrence. SFA and VFA accumulation were independently associated with episode recurrence (all p < 0.05), and SFA had a stronger association than VFA did. Conclusions: In young people, SFA accumulation is an independent and early risk factor for the occurrence and recurrence of stone episodes. Subcutaneous fat could be a convenient and effective indicator to assess the risk of stone episodes before the development of metabolic disorders. [ABSTRACT FROM AUTHOR]

Central obesity is genetically complex, and its exponential increase in the last decades have made it a critical public health issue. The Lyon Hypertensive (LH) rat is a well-characterized hypertensive model that also exhibits spontaneous and profound differences in body weight and adiposity, relative to its metabolically healthy control, the Lyon Normotensive (LN) rat. The mechanisms underlying the body weight differences between these strains are not well-understood, thus a congenic model (LH17LNa) was developed where a portion of the proximal arm of LN chromosome 17 is introgressed on the LH genomic background to assess the contribution of LN alleles on obesity features. Male and female LH17LNa rats were studied, but male congenics did not significantly differ from LH in this study. Female LH17LNa rats exhibited decreases in total body growth, as well as major alterations to their body composition and adiposity. The LH17LNa female rats also showed decreases in metabolic rate, and a reduction in food intake. The increased adiposity in the female LH17LNa rats was specific to abdominal white adipose tissue, and this phenomenon was further explained by significant hypertrophy in those adipocytes, with no evidence of adipocyte hyperplasia. Sequencing of the parental strains identified a novel frameshift mutation in the candidate gene Ercc6l2 , which is involved in transcription-coupled DNA repair, and is implicated in premature aging. The discovery of the significance of Ercc6l2 in the context of female-specific adipocyte biology could represent a novel role of DNA repair failure syndromes in obesity pathogenesis. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for canine health but there has been no study on the tendency of body fat accumulation naturally occurring in obese dogs. This retrospective observational study aims to evaluate the tendency to accumulate visceral and subcutaneous fat using computed tomography (CT) in naturally occurring obese dogs. The study included 15 dogs with a body condition score of 8 or 9 that underwent abdominal CT scans. Total fat area (TA), visceral fat area (VA), subcutaneous fat area (SA) and body area (BA) were measured by non-contrast transverse image at the third lumbar vertebra (L3) and the sixth lumbar vertebra (L6). TA, VA and SA were divided by the length of the L6 body to account for different body size. The ratio (rTA, rVA, and rSA) was then calculated. rTA and rVA were significantly higher at L3 and rSA was significantly higher at L6. TA/BA and VA/SA were analyzed at L3 and L6, respectively. No difference in TA/BA between L3 and L6 was shown while the VA/SA was significantly higher at L3 than at L6 (P = 0.001). There was no difference of visceral and subcutaneous fat distribution between the male and female groups. The findings of the present study suggested that visceral and subcutaneous fat are accumulated at L3 and L6, respectively, and obese dogs tend to accumulate more visceral than subcutaneous fat. [ABSTRACT FROM AUTHOR]

Aims: To examine whether changes in objectively measured physical activity (PA) are associated with weight loss and changes in body composition and fat distribution in response to weight‐loss diet interventions. Methods: This study included 535 participants with overweight/ obesity, who were randomly assigned to four weight‐loss diets varying in macronutrients. PA was measured objectively with pedometers, and body composition and fat distribution were measured using dual‐energy X‐ray absorptiometry and computed tomography scans at baseline, 6 months and 24 months. Results: From baseline to 6 months, when the maximum weight loss was achieved, each 1000‐steps/d increment in PA was associated with a greater reduction in body weight (β[SE] = −0.48[0.11]) and waist circumference (β[SE] = −0.49[0.12]). Similar inverse associations were found in changes in body composition and fat distribution (P < 0.05 and false discovery rate qvalue < 0.1 for all). The trajectory of the above adiposity measures across the 24‐month intervention period differed between the patterns of PA change. Participants with the largest increase in PA maintained their weight loss from 6 months to 24 months, while those with a smaller increase in PA regained their weight. In addition, dietary fat or protein intake significantly modified the associations between changes in PA and changes in body weight and waist circumference over 24 months (P∆PA*diet < 0.05). Conclusions: Changes in objectively measured PA were inversely related to changes in body weight, body composition and fat distribution in response to weight‐loss diets, and such associations were more evident in people on a high‐fat or average‐protein diet compared with a low‐fat or high‐protein diet. [ABSTRACT FROM AUTHOR]

Background: Adiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females. Methods: Thirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses. Results: Mitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = − 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = − 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr. Conclusions: These novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Emerging evidence suggests a fat depot-specific relationship with bone mineral density (BMD) in children, particularly in those who are overweight/obese. However, this has not yet been investigated in detail in children with Prader–Willi syndrome (PWS), a genetic syndrome characterized by a decreased lean mass (LM) and increased fat mass (FM). The objective of this study is to investigate the relationships of LM and FM, particularly fat distribution, with bone mineral parameters. This is a retrospective and cross-sectional study. Forty-seven prepubertal Japanese children with PWS (22 males, mean age: 6.86 years) were included. No subjects had type 2 diabetes mellitus or osteoporotic medications. LM, FM, and BMD and bone mineral content in the total body less head and the lumbar spine were measured using dual-energy x-ray absorptiometry, in addition to subcutaneous/visceral adipose tissue (SAT/VAT), and the ratio of VAT to SAT (V/S) by computed tomography at the umbilical level. Bone mineral apparent density was calculated to correct for bone size. LM positively correlated with bone mineral parameters after controlling for age, sex, growth hormone (GH) treatment, and FM. Although FM did not correlate with bone mineral parameters, compartment-specific analysis revealed that SAT positively and V/S negatively correlated with bone mineral parameters after controlling for age, sex, GH treatment and LM. A compartment-specific effect of FM on bone mineral parameters was noted such that SAT was a positive predictor for BMD independent of LM in prepubertal children with PWS. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to assess the associations between adiposity distribution and cardiometabolic risk factors among overweight and obese adults in China, and to demonstrate the sex differences in these associations. Methods A total of 1221 participants (455 males and 766 females) were included in this study. Percentage of body fat (PBF) of the whole body and regional areas, including arm, thigh, trunk, android, and gynoid, were measured by the dual-energy X-ray absorptiometry method. Central adiposity was measured by waist circumference. Clustered cardiometabolic risk was defined as the presence of two or more of the six cardiometabolic risk factors, namely, high triglyceride, low high density lipoprotein, elevated glucose, elevated blood pressure, elevated high sensitivity C-reactive protein, and low adiponectin. Linear regression models and multivariate logistic regression models were used to assess the associations between whole body or regional PBF and cardiometabolic risk factors. Results In females, except arm adiposity, other regional fat (thigh, trunk, android, gynoid) and whole-body PBF are significantly associated with clustered cardiometabolic risk, adjusting for age, smoking, alcohol drinking, physical activity, and whole-body PBF. One-SD increase in Z scores of the thigh and gynoid PBF were significantly associated with 80 and 78% lower odds of clustered cardiometabolic risk (OR: 0.20, 95%CI: 0.12–0.35 and OR: 0.22, 95%CI: 0.12–0.41). Trunk, android and whole-body PBF were significantly associated with higher odds of clustered risk with OR of 1.90 (95%CI:1.02–3.55), 2.91 (95%CI: 1.75–4.85), and 2.01 (95%CI: 1.47–2.76), respectively. While in males, one-SD increase in the thigh and gynoid PBF are associated with 94% (OR: 0.06, 95%CI: 0.02–0.23) and 83% lower odds (OR: 0.17, 95%CI: 0.05–0.57) of clustered cardiometabolic risk, respectively. Android and whole-body PBF were associated with higher odds of clustered cardiometabolic risk (OR: 3.39, 95%CI: 1.42–8.09 and OR: 2.45, 95%CI: 1.53–3.92), but the association for trunk PBF was not statistically significant (OR: 1.16, 95%CI: 0.42–3.19). Conclusions Adiposity distribution plays an important role in the clustered cardiometabolic risk in participants with overweight and obese and sex differences were observed in these associations. In general, central obesity (measured by android PBF) could be the best anthropometric measurement for screening people at risk for CVD risk factors for both men and women. Upper body fat tends to be more detrimental to cardiometabolic health in women than in men, whereas lower body fat is relatively more protective in men than in women.

Summary: Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.

Central obesity is genetically complex, and its exponential increase in the last decades have made it a critical public health issue. The Lyon Hypertensive (LH) rat is a well-characterized hypertensive model that also exhibits spontaneous and profound differences in body weight and adiposity, relative to its metabolically healthy control, the Lyon Normotensive (LN) rat. The mechanisms underlying the body weight differences between these strains are not well-understood, thus a congenic model (LH17LNa) was developed where a portion of the proximal arm of LN chromosome 17 is introgressed on the LH genomic background to assess the contribution of LN alleles on obesity features. Male and female LH17LNa rats were studied, but male congenics did not significantly differ from LH in this study. Female LH17LNa rats exhibited decreases in total body growth, as well as major alterations to their body composition and adiposity. The LH17LNa female rats also showed decreases in metabolic rate, and a reduction in food intake. The increased adiposity in the female LH17LNa rats was specific to abdominal white adipose tissue, and this phenomenon was further explained by significant hypertrophy in those adipocytes, with no evidence of adipocyte hyperplasia. Sequencing of the parental strains identified a novel frameshift mutation in the candidate gene Ercc6l2, which is involved in transcription-coupled DNA repair, and is implicated in premature aging. The discovery of the significance of Ercc6l2 in the context of female-specific adipocyte biology could represent a novel role of DNA repair failure syndromes in obesity pathogenesis.

BackgroundUrinary stones usually start at a young age and tend to recur. Therefore, preventing stone occurrence and recurrence in young people is crucial. We aimed to investigate the association between subcutaneous adipose tissue, visceral adipose tissue, and stone episodes in young people.MethodsWe retrospectively studied patients aged below 40 years with kidney or ureteral stones. Data on demographic and metabolic characteristics, urolithiasis history, subcutaneous fat area (SFA), and visceral fat area (VFA) were collected. We evaluated the association between SFA or VFA and the occurrence or recurrence of stone episodes using binary logistic regression and Poisson regression analyses.ResultsIn total, 120 patients were included. Abdominal obesity, overweight or obesity, dyslipidemia, metabolic syndrome, SFA, and VFA increased with the number of stone episodes (all p < 0.05). The increase in SFA was independently associated with episode occurrence (p = 0.015). Patients with an SFA > 97 cm2 had a higher risk of episode occurrence. SFA and VFA accumulation were independently associated with episode recurrence (all p < 0.05), and SFA had a stronger association than VFA did.ConclusionsIn young people, SFA accumulation is an independent and early risk factor for the occurrence and recurrence of stone episodes. Subcutaneous fat could be a convenient and effective indicator to assess the risk of stone episodes before the development of metabolic disorders.

Belly is a very popular pork cut composed of different layers of fat and muscle tissue. This work aims to investigate the effect of belly fatness on the morphological, mechanical (firmness) and compositional characteristics of fresh pork bellies and the distribution of the fat within the belly slice. A total of 182 bellies, selected to ensure variability of fatness, sexes and genotypes, were scanned by computed tomography (CT) to determine the fat content which, together with the genotype, led to the formation of 5 classes: F1 class below 26%, F2 class from 26% to 33.9%, and F3 class above 33.9% of fat content from common commercial crossbred pigs; F4 class with an average fatness of 47.3% from pure Duroc pigs; and last, F5 class with 62.6% average fat content from Iberian×Duroc pigs. The distribution of the fat in the central belly slice obtained by CT revealed important differences by region although the fat content was proportional to the overall fatness of the belly. Both belly weight and belly firmness increased with higher fatness. In bellies from common commercial pigs, an increase of SFA and MUFA and a decrease of PUFA as fatness increased was observed. This study highlights variations in belly characteristics among different fat classes, indicating considerable differences in the quality of bellies currently available in the market. This may influence producers and consumers acceptability such that fat content could be considered as a quality criterion to pre-classify bellies and better match the raw product with its final destination. • Skin tension as an indicator of cohesiveness between skin and fat (firmness). • Belly firmness increases and skin thickness decreases with belly fatness. • Fat distribution along the slice is variable but proportional to belly fatness. • In common pigs fatter bellies are thicker, firmer, longer and with more SFA. • Fatness could be used as a criterion to select bellies with the required quality. [ABSTRACT FROM AUTHOR]

In this study, we examined the impact of adding Lactobacillus to the diet on fat distribution and meat quality of Sunit lambs. For 90 days, twenty-four lambs (19.31 ± 0.47 kg) were fed diets that contained 0 (NP), 6 (P1), 12 (P2), or 24 (P3) g of Lactobacillus casei /d. The results suggested that dietary supplementation with Lactobacillus decreased serum triglyceride in Sunit lambs (P < 0.001). The loin muscle area displayed notable increases in the P1 group (P < 0.05). Meanwhile, tail and visceral fat deposition of lambs were reduced when Lactobacillus was added to the diet (P < 0.05). Compared with the NP group, the values of shear force and cooking loss of in the P1 group exhibited a significant reduction, and intramuscular fat content increased significantly (P < 0.05). Additionally, the P1 group showed an increase in polyunsaturated fatty acids and a decrease in saturated fatty acids in the longissimus thoracis and biceps femoris muscles (P < 0.05). The P1 group showed downregulation of protein kinase AMP-activated catalytic subunit alpha 2 (AMPKα2) and carnitine palmitoyltransferase 1B expression in the longissimus thoracis muscle (P < 0.05). However, there was an upregulation of acetyl-CoA carboxylase (ACC), sterol regulatory element binding transcription factor 1 (SREBF1), and fatty acid synthase (FASN) expression (P < 0.05). In conclusion, feeding Sunit lambs 6 g/d of Lactobacillus as a dietary supplement may be a valuable way to improve fat distribution and meat quality. The AMPK/ACC and AMPK/SREBF1/FASN signaling pathways may be involved in this outcome. • Lactobacillus supplementation improved the lipid metabolism in Sunit lamb. • Supplementing with 6 g/d of Lactobacillus increased intramuscular fat accumulation. • Adding 6 g/d of Lactobacillus improved the fatty acid composition of Sunit lamb. • AMPK signaling pathway has a critical role in improved fat deposition in Sunit lamb. [ABSTRACT FROM AUTHOR]

[Display omitted] Upper-body adiposity is adversely associated with metabolic health whereas the opposite is observed for the lower-body. The neck is a unique upper-body fat depot in adult humans, housing thermogenic brown adipose tissue (BAT), which is increasingly recognised to influence whole-body metabolic health. Loss of BAT, concurrent with replacement by white adipose tissue (WAT), may contribute to metabolic disease, and specific accumulation of neck fat is seen in certain conditions accompanied by adverse metabolic consequences. Yet, few studies have investigated the relationships between neck fat mass (NFM) and cardiometabolic risk, and the influence of sex and metabolic status. Typically, neck circumference (NC) is used as a proxy for neck fat, without considering other determinants of NC, including variability in neck lean mass. In this study we develop and validate novel methods to quantify NFM using dual x-ray absorptiometry (DEXA) imaging, and subsequently investigate the associations of NFM with metabolic biomarkers across approximately 7000 subjects from the Oxford BioBank. NFM correlated with systemic insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR), low-grade inflammation (plasma high-sensitivity C-Reactive Protein; hsCRP), and metabolic markers of adipose tissue function (plasma triglycerides and non-esterified fatty acids; NEFA). NFM was higher in men than women, higher in type 2 diabetes mellitus compared with non-diabetes, after adjustment for total body fat, and also associated with overall cardiovascular disease risk (calculated QRISK3 score). This study describes the development of methods for accurate determination of NFM at scale and suggests a specific relationship between NFM and adverse metabolic health. [ABSTRACT FROM AUTHOR]

Background and Aims: Cardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.Methods and Results: We conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574-456,823). Multiple loci reached genome-wide levels of significance (N = 145-333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10-8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP.Conclusions: Our analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets. [ABSTRACT FROM AUTHOR]

Context: Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking predominantly noncoding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss of function (LoF) would be of most therapeutic benefit. Objective: This work aimed to identify genes/proteins involved in determining fat distribution. Methods: We combined the power of genome-wide analysis of array-based rare, nonsynonymous variants in 450 562 individuals in the UK Biobank with exome-sequence-based rare LoF gene burden testing in 184 246 individuals. Results: The data indicate that the LoF of 4 genes (PLIN1 [LoF variants, P = 5.86 × 10–7], INSR [LoF variants, P = 6.21 × 10–7], ACVR1C [LoF + moderate impact variants, P = 1.68 × 10–7; moderate impact variants, P = 4.57 × 10–7], and PDE3B [LoF variants, P = 1.41 × 10–6]) is associated with a beneficial effect on body mass index–adjusted waist-to-hip ratio and increased gluteofemoral fat mass, whereas LoF of PLIN4 (LoF variants, P = 5.86 × 10–7 adversely affects these parameters. Phenotypic follow-up suggests that LoF of PLIN1, PDE3B, and ACVR1C favorably affects metabolic phenotypes (eg, triglycerides [TGs] and high-density lipoprotein [HDL] cholesterol concentrations) and reduces the risk of cardiovascular disease, whereas PLIN4 LoF has adverse health consequences. INSR LoF is associated with lower TG and HDL levels but may increase the risk of type 2 diabetes. Conclusion: This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counterintuitive insight into the potential consequences of targeting these molecules therapeutically. [ABSTRACT FROM AUTHOR]