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Myositis-specific antibodies (MSAs) facilitate grouping children with juvenile dermatomyositis (DM) into distinct phenotypes. The first aim of this study was to investigate the link between anti-p155/140 and lipodystrophy as determined by dual x-ray absorptiometry (DXA) assessment of fat distribution. The second aim was to examine the relationship between anti-p155/140 and damage to the nailfold capillary system.Children with juvenile DM followed for a minimum of 5 years were included. The study population was divided into 3 groups (anti-p155/140, other MSA, and MSA negative). Lipodystrophy was assessed by physician assessment and DXA fat distribution (trunk-to-leg fat ratio). Documentation of nailfold capillary end row loops (ERLs) was obtained at diagnosis.A total of 96 subjects (44% anti-p155/140, 23% other MSA, 33% MSA negative) were included. There was no significant difference in age, disease activity scores, or lipodystrophy between the 3 groups. The trunk-to-leg fat ratios were similar among the 3 groups at different time points. However, the anti-p155/140 group had significantly decreased ERL counts (P = 0.006) at baseline as well as a prolonged duration of untreated disease at diagnosis (P = 0.027). Also, the anti-p155/140 group had fewer patients with a monophasic disease course than the other 2 groups (P = 0.008).Generalized lipodystrophy frequency was equivalent in all 3 groups based on physician assessments and trunk-to-leg fat ratios. The anti-p155/140 group had a greater loss of ERLs, suggesting that this MSA may impact the vascular component of juvenile DM.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference and waist-to-hip ratio adjusted for body mass index (WCadjBMI, WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at eight-to-ten weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at one year in 5 lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One standard deviation higher PS related to smaller one-year change in WCadjBMI in the lifestyle intervention arms at year 1, and thus predicted poorer response (beta=0.007, SE=0.003, p=0.03) among White participants overall and in White men (beta=0.01, SE=0.004, p=0.01). At average weight loss, this amounted to 0.20-0.28 cm per standard deviation. No significant findings emerged in White women, African American men, for the 8-10 week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk relates to change in WCadjBMI with lifestyle intervention but the effects are small and not of sufficient magnitude to be clinically significant.

Rationale and Objectives Molecular studies have shown the changes in bone marrow fat in relation to altered hematopoiesis. This study aims to investigate the changes in the bone marrow fat in patients affected by β-thalassemia by using chemical shift-encoded (CSE)–MRI. Materials and Methods Twenty-three subjects, comprising of six healthy (17-31 years old) and 17 β-thalassemia subjects (19-39 years old), were scanned using a multiecho fast low angle shot sequence (0.94 × 0.94 × 3.00 mm3) and a stimulated echo acquisition mode sequence using 3T MRI. Bone marrow proton density fat fraction (PDFF) was quantified in the left femur of each subject. Regression and Bland-Altman analysis were used to analyze agreement between CSE-MRI and 1H-MRS. PDFF distribution was analyzed using Hartigan's dip test and the computed Wasserstein distances. Jonckheere-Terpstra trend analysis was performed to evaluate the effect of disease severity on PDFF distribution. Results An excellent agreement was found between PDFF measured using CSE-MRI with 1H-MRS (R2 = 0.91; bias =-1.41%). Healthy subjects showed left-skewed or bimodal PDFF distribution while β-thalassemia subjects showed bimodal, normal or right-skewed distribution. Jonckheere-Terpstra test shows that PDFF distribution was increasingly different from the norm as disease severity increased (TJT = 166.0, z = 3.806, p Conclusion CSE-MRI is a promising tool to demonstrate spatial changes and variability in marrow fat distribution, resulting from ineffective erythropoiesis.

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.

We investigated the prospective associations of body composition with cardiac structure and function and explored effect modification by sex and whether inflammation was a mediator in these associations. Total body (BF), trunk (TF) and leg fat (LF), and total lean mass (LM) were measured at baseline by a whole body DXA scan. Inflammatory biomarkers and echocardiographic measures were determined both at baseline and follow-up in the Hoorn Study (n = 321). We performed linear regression analyses with body composition measures as determinant and left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) or left atrial volume index (LAVI) at follow-up as outcome. Additionally, we performed mediation analysis using inflammation at follow-up as mediator. The study population was 67.7 ± 5.2 years and 50% were female. After adjustment, BF, TF and LF, and LM were associated with LVMI with regression coefficients of 2.9 (0.8; 5.1)g/m2.7, 2.3 (0.6; 4.0)g/m2.7, 2.0 (0.04; 4.0)g/m2.7 and − 2.9 (− 5.1; − 0.7)g/m2.7. Body composition measures were not associated with LVEF or LAVI. These associations were not modified by sex or mediated by inflammation. Body composition could play a role in the pathophysiology of LV hypertrophy. Future research should focus on sex differences in regional adiposity in relation with diastolic dysfunction.

Objective We aim to investigate a possible relationship between acute pancreatitis (AP) and body fat and muscle parameters in computed tomography (CT). Methods Computed tomography images of 107 patients with AP were scored in terms of AP severity using the modified CT severity index. Muscle mass, muscle mass index, visceral and subcutaneous adipose tissue area, multifidus muscle/fat attenuation ratio, total psoas index (TPI) and Hounsfield units average calculation (HUAC) values were performed. Results Total psoas index and HUAC of mild AP cases were significantly higher than those with moderate and severe AP. The TPI of patients with severe pancreatic necrosis were found to be significantly lower than those without necrosis. Hounsfield units average calculation of cases without necrosis were significantly higher than those with severe necrosis in the pancreas. Conclusions Our study indicated that lower volume and density of psoas muscle associated with worse CT severity score and larger pancreatic necrosis in patients with AP.

The influence of milk-banking processes on nutrients in donor human milk (DHM) is largely unknown. Previous studies have measured nutrients between pools of DHM, but within-pool nutrient differences (between bottles from the same pool) have yet to be elucidated. The objective of this study was to gain a better understanding of the effect of different mixing characteristics on the distribution of fat, protein, IgA, and lysozyme in bottled, raw DHM. Pools of DHM were created in a laboratory setting according to published human milk-banking guidelines and assigned to a mixing treatment (mixing during bottling method, pooling container material, and refrigerated hold time). Four mixing protocols using glass pooling containers and a 1-h refrigerated hold time were tested: control (no mixing during bottling); manual-A (Man-A, hand swirl after pouring 3 bottles); manual-B (Man-B, hand swirl after pouring every bottle); and mechanical-G (Mech-G, continuous stirring with a magnet). As secondary objectives, we compared the effect of a glass and a plastic pooling container with mechanical mixing (mechanical-P, Mech-P), and compared refrigerated delays of 1 and 24 h before bottling with manual mixing (manual-A24, Man-A24). To control for differences in nutrient content, comparisons between treatments were made using absolute percent difference from the treatment-specific mean; and comparisons within a treatment were made using the ratio of fat content in a bottle to fat content in the first bottle of the same pool. We did not observe differences in nutrient distribution between Man-A, Man-B, and Mech-G in pools held for 1 h, but all were significantly different from the control for fat. There were no differences between glass or plastic pooling containers when mechanical mixing was used. Holding a pool in the refrigerator for 24 h before bottling created significantly greater fat distribution than holding a pool for 1 h. Outcomes were the result of controlled experiments. In summary, manual and mechanical mixing of 1,700-mL DHM pools produces similar fat and protein distributions when DHM is pooled and bottled after a 1-h hold time. When DHM is held for 24 h before bottling, more research is needed to determine the duration of initial mixing needed to reduce fat variability between bottles.

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.Thirty-two non-diabetic NAFLD with liver biopsy (BMI 21.4-34.7 kg/mIntrahepatic 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.These findings propose VF as an early indicator of NAFLD progression independently of BMI, which may allow for evidence-based prevention and intervention strategies.

Background: Bariatric surgery leads to long-term remission and reduced incidence of diabetes, hypertension, and dyslipidemia. Short-term studies suggest reduction in specific fat depots may be more predictive of health improvement than reduced body mass index (BMI). Visceral, subcutaneous, epicardial, and liver fat, measured 11 years after bariatric surgery, were associated with long-term remission and incidence of diabetes, dyslipidemia, and hypertension. Methods: Fat depots an average of 11 (maximum 14) years after surgery were quantified by noncontrast computed tomography in subjects who did (N = 261; 86% gastric bypass) or did not (N = 243) have bariatric surgery. Multiple regression related fat depots to disease endpoints with and without adjustment for change in BMI and surgical status. Results: Visceral fat was 42% lower, subcutaneous fat 20% lower, epicardial fat 30% lower, and liver-to-spleen density ratio 9% higher at follow-up in the bariatric surgery group compared with the nonsurgery group (all P

Summary Background & Aims The rise in the prevalence of childhood obesity has increased the demand for accurately evaluating body fatness in pediatric population. The aim of this study was to provide a series of sex- and age-specific body fat reference centiles for evaluating total body fat development and fat distribution in Chinese children and adolescents using dual-energy x-ray absorptiometry (DXA). Methods A nationwide sample of Chinese children and adolescents aged 3-18 years (n=12,790) was drawn from a cross-sectional survey of the China Child and Adolescent Cardiovascular Health study (2013-2019). Fat measurements, including total fat mass index (FMI), total body fat percentage (BF%), regional FMI, trunk to leg (T/L) fat ratio and android to gynoid (A/G) fat ratio, were derived from whole body DXA scans. Sex- and age-specific centiles were estimated using the lambda-mu-sigma method and then compared with values derived from the US National Health and Nutrition Examination Survey (1999-2004) and Korean National Health and Nutrition Examination Survey (2008-2011). Results During early childhood, almost all body fat parameters decreased with age, except an increase in A/G ratio. After 7 years onward, drastic upward trends of total FMI and BF% were exhibited in boys till 10 years, followed by opposite downward trends during 11-14 years; while sustained increase of FMI was shown in girls across ages accompanied by relatively constant BF% levels. Meanwhile, steady increases were noticed for A/G ratio and T/L ratio, which were more pronounced in boys. In addition, the proposed body fat references were much lower than the US but similar to Koreans despite of subtle differences. Conclusions This is the first study to present a set of DXA-based body fat reference for Chinese children and adolescents aged 3-18 years. The new reference provides clinicians and researchers a useful tool for assessing body fat development and distribution patterns across the periods from early childhood to adolescence.

Objective: Menopause increases the risk of cardiovascular disease (CVD) which in part has been attributed to the rises in cholesterol and blood pressure (BP). This study examined the hypothesis that menopausal changes in body composition and regional fat depots relate to the change in CVD risk factors. Methods: A prospective recall study was designed to capture premenopausal women to be reexamined soon after menopause. A total of 97 women from the Oxford Biobank underwent dual x-ray absorptiometry, blood biochemistry and BP readings pre- and post-menopause. Results: Despite minimal changes in body weight over the 5.1±0.9 year follow-up period, there was an increase in total fat mass and a decline in lean mass, where the proportional change of regional fat mass was the greatest for the visceral fat depot (+22%, p Conclusion: The increase in CVD risk factor burden across menopause may not be driven by changes in body composition, rather by functional changes in end organs such as adipose tissue and liver.

Objective: The aim of this study was to identify the effects of menopausal and body composition statuses on measures of total and regional body composition and dyslipidemia in women. Methods: Sedentary, non-smoking women (N = 212), not currently treated for dyslipidemia were grouped based on 2 categories: (1) menstrual status: premenopausal or postmenopausal and (2) body composition status: normal weight (NW; BMI < 25 kg/m2 and body fat (BF) < 36%), normal weight obese (NWO; BMI < 25 kg/m2 and BF > 36%), or obese (BMI > 25 kg/m2 and BF > 36%), to determine differences in total and regional body composition and measures of lipid and lipoprotein-cholesterol concentrations. Results: Overall, a greater prevalence of NWO was observed in postmenopausal versus premenopausal women. Being postmenopausal was associated with higher TC, LDL-C, non-HDL-C, HDL-C, and HDL3-C. Premenopausal NWO women had elevated LDL-C and VLDL-C comparable to obese women. Postmenopausal NWO women had elevated Tg and VLDL-C and lower HDL-C similar to obese women. Conclusions: Menopausal status was not associated with differences in fat distribution, however, the age-related differences in lipids and lipoproteins appear to be due to a difference in menopausal status exacerbated in women who are NWO.

Obesity-associated metabolic illnesses are increasing at an alarming rate in Asian countries. A common feature observed in the Asian population is a higher incidence of abdominal obesity—the “skinny-fat” Asian syndrome. In this review, we critically evaluate the relative roles of genetics and environmental factors on fat distribution in Asian populations. While there is an upward trend in obesity among most Asian countries, it appears particularly conspicuous in Malaysia. We propose a novel theory, the Malaysian gene-environment multiplier hypothesis, which explains how ancestral variations in feast-and-famine cycles contribute to inherited genetic predispositions that, when acted on by modern-day stressors—most notably, urbanization, westernization, lifestyle changes, dietary transitions, cultural pressures, and stress—contribute to increased visceral adiposity in Asian populations. At present, the major determinants contributing to visceral adiposity in Asians are far from conclusive, but we seek to highlight critical areas for further research.

Background: Fat distribution is associated with chronic diseases and birth weight may influence fat distribution throughout life. Our aim was to compare fat distribution in children born extremely ...

Obesity is associated with chronic low back pain (CLBP), but the association between fat distribution and CLBP is unclear. This cross-sectional study evaluated the relationship using the Korean National Health and Nutrition Examination Survey data. A total of 10,606 adults (average age: 45.4, female: 57.1%) were included. We estimated the regional fat distribution, waist circumference, and body fat proportion, compared the values in people with and without CLBP, and stratified the estimates by sex and obesity status using a multivariable linear model. There were no statistically significant differences in the average waist circumference between the people with and without CLBP (p = 0.731) and the average fat proportion between those with and without CLBP (p = 0.731). The average regional fat distribution was significantly higher in the people with CLBP than in those without CLBP, in the upper limbs (11.4%, 95% confidence interval [CI]: [11.3, 11.5] vs. 11.2%, 95% CI: [11.1, 11.3], p < 0.05) and in the lower limbs (31.9%, 95% CI: [31.6, 32.2] vs. 31.4%, 95% CI: [31.2, 31.6], p < 0.01). More obvious among men, fat distribution in the lower limbs is higher than in people without obesity (p < 0.001). People with CLBP tend to have a higher fat distribution in the limbs than those without it and obese people with CLBP would need to reduce the fat in the lower limbs.

Background The aim of the study was to assess changes in body composition in patients subjected to laparoscopic sleeve gastrectomy (LSG). Methods Changes in body composition following LSG were determined in a group of 155 patients with obesity (117 women and 38 men), with dual-energy X-ray absorptiometry (DXA). Whole body fat mass (FM) and lean body mass (LBM) were determined, and abdominal fat mass (AbdF) was assessed within the region extending from the top of the pubic bone up to the line between 12th thoracic and 1st lumbar vertebras. Results Over the period of 12 months following LSG, body mass index decreased by 28.2 ± 9.0% (p p p p p p Conclusions Over the period of 12 months following LSG, the reduction of FM was more than twice as much as decrease of LBM. The loss of AbdF was slower than a loss of peripheral subcutaneous fat.

Aims We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO2) in male patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) 25 kg/m2 with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO2 was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio 0.55 to be independently associated with reduced peak VO2 adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030–14.730, P = 0.045). Conclusions Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.

Background Increasing attention has been drawn on the assessment of body composition phenotypes, since the distribution of soft tissue influences cardio-metabolic risk. Dual-energy X-ray absorptiometry (DXA) is a validated technique to assess body composition. European reference values from population-based cohorts are rare. Aims To provide age- and sex-related reference values of body composition parameters and visceral adipose tissue (VAT) mass, and for lean mass index (LMI) with regard to fat mass index (FMI) quantities and BMI categories. Methods GE-Lunar Prodigy DXA scans of 10.894 participants, aged 18–81 years, recruited from 2011 to 2019 by the Austrian LEAD study, a population-based cohort study, have been used to construct reference curves using the LMS method. Parameters assessed are FMI, LMI, appendicular LMI, fat mass ratios android/gynoid and trunk/limbs, and VAT. Results All lean mass and fat mass parameters indicating central fat accumulation were higher in men, whereas other fat mass indices were higher in women. LMI differed between each FMI subgroup (low vs. normal, low vs. high, normal vs. high), and BMI category in all ages and LMI increased with FMI and BMI classes. VAT mass was higher in men compared with women and increased across all age groups within both sexes. Conclusion The present study provides age- and sex-related reference values for European adults aged 18–81 years for body composition parameters and VAT mass for Lunar Prodigy DXA. In addition, this study reports LMI reference values with regard to fat mass quantities, showing a positive association with increasing FMI percentiles and BMI categories., European Journal of Clinical Nutrition, 74 (8), ISSN:0954-3007, ISSN:1476-5640

Introduction Hip fractures can be divided into intra-capsular and extra-capsular fracture based on fracture location; these two types of fracture have different pathogeneses, treatments and prognoses. Many factors influence the patterns of hip fractures, including the injury mechanism, areal bone mineral density and the geometry of the hip. However, the relationship between body composition and hip fracture pattern has not yet been discussed. In this investigation, an analysis of the body compositions of geriatric patients with hip fractures were conducted to identify differences between fat and muscle distributions between patients with intra- and extra-capsular hip fractures. Material and methods From December 2017 to February 2019, 139 patients with a hip fracture were prospectively enrolled in this study. The groups of patients that were diagnosed as having intra- and extra-capsular hip fractures were compared in terms of patient demographics, pre-operative laboratory data, bone mineral density (BMD) and body composition including muscle and fat distributions obtained using dual-energy X-ray absorptiometry (DXA) . Results Eighty-six and 53 patients were diagnosed with intra-capsular and extra-capsular hip fractures, respectively. A significantly higher serum glucose level, a lower hemoglobin level, a lower T-score level in the proximal femur region, a lower T-score of all parts of interest, and a lower percentage fat content on the region of bilateral proximal hips (gynoid region) and in the lower limb region, were observed in patients with an extra-capsular hip fracture than in those with an intra-capsular hip fracture. However, with all confounding factors controlled for, only the T-score at the proximal femur, percentage fat content in the region of bilateral proximal hips and the ratio of android fat content to gynoid fat content (A/G ratio) are the most relevant factors in predicting the patterns of hip fracture in geriatric patients after falling. Conclusion This work demonstrates that lower fat content in the region of bilateral proximal hips and a lower BMD on the proximal femur may predict greater vulnerability of geriatric patients to extra-capsular rather than intra-capsular hip fracture after a falling accident.

BackgroundBone mineral density (BMD) loss is a major complication of menopause, and this loss is closely associated with Fat mass (FM). The relationship between FM, fat distribution (FD), and BMD in postmenopausal women, however, remains incompletely understood. The present study was thus developed to explore these associations between body fat accumulation, FD, and BMD among non-obese postmenopausal women over the age of 60.MethodsThis was a cross-sectional analysis of 357 healthy postmenopausal women between the ages of 60.2 and 86.7 years. Dual-energy X-ray absorptiometry (DXA) was utilized to measure total and regional BMD as well as fat-related parameters including total FM, android and gynoid fat, body fat percentage (BF%), and total lean mass (LM) for all subjects. The android-to-gynoid fat ratio (AOI) was used to assess FD. Pearson’s correlation testing and multiple regression analyses were used to explore relationships among AOI, LM, FM, and BMD.ResultsBoth LM and FM were positively correlated with total and regional BMD in univariate analysis (all P < 0.01), whereas BMD was not significantly associated with AOI in any analyzed site other than the head. Multivariate linear regression models corrected for age, height, and years post-menopause, revealed a sustained independent positive relationship between FM and BMD (standard β range: 0.141 – 0.343, P < 0.01). The relationship between FM and BMD was unaffected by adjustment for LM (standard β range: 0.132 – 0.258, P < 0.01), whereas AOI had an adverse impact on BMD at most analyzed skeletal sites (total body, hip, femoral neck, arm, leg, and head) (standard β range: −0.093 to −0.232, P < 0.05). These findings were unaffected by using BF% in place of FM (standard β range: −0.100 to −0.232, P < 0.05).ConclusionsIn this cohort of non-obese postmenopausal women over the age of 60 from China, total FM was positively associated with BMD, while AOI was negatively correlated with BMD. As such, a combination of proper weight gain and the control of central obesity may benefit the overall bone health of women after menopause.

BackgroundN6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications on mRNA influencing mRNA metabolism. There is emerging evidence for its implication in metabolic disease. No comprehensive analyses on gene expression of m6A regulators in human adipose tissue, especially in paired adipose tissue depots, and its correlation with clinical variables were reported so far. We hypothesized that inter-depot specific gene expression of m6A regulators may differentially correlate with clinical variables related to obesity and fat distribution.MethodsWe extracted intra-individually paired gene expression data (omental visceral adipose tissue (OVAT) N=48; subcutaneous adipose tissue (SAT) N=56) of m6A regulators from an existing microarray dataset. We also measured gene expression in another sample set of paired OVAT and SAT (N=46) using RT-qPCR. Finally, we extracted existing gene expression data from peripheral mononuclear blood cells (PBMCs) and single nucleotide polymorphisms (SNPs) in METTL3 and YTHDF3 from genome wide data from the Sorbs population (N=1049). The data were analysed for differential gene expression between OVAT and SAT; and for association with obesity and clinical variables. We further tested for association of SNP markers with gene expression and clinical traits.ResultsIn adipose tissue we observed that several m6A regulators (WTAP, VIRMA, YTHDC1 and ALKBH5) correlate with obesity and clinical variables. Moreover, we found adipose tissue depot specific gene expression for METTL3, WTAP, VIRMA, FTO and YTHDC1. In PBMCs, we identified ALKBH5 and YTHDF3 correlated with obesity. Genetic markers in METTL3 associate with BMI whilst SNPs in YTHDF3 are associated with its gene expression.ConclusionsOur data show that expression of m6A regulators correlates with obesity, is adipose tissue depot-specific and related to clinical traits. Genetic variation in m6A regulators adds an additional layer of variability to the functional consequences.

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.

Background Obesity predisposes individuals to multiple cardiometabolic disorders, including type 2 diabetes (T2D). As body mass index (BMI) cannot reliably differentiate fat from lean mass, the metabolically detrimental abdominal obesity has been estimated using waist-hip ratio (WHR). Waist-hip ratio adjusted for body mass index (WHRadjBMI) in turn is a well-established sex-specific marker for abdominal fat and adiposity, and a predictor of adverse metabolic outcomes, such as T2D. However, the underlying genes and regulatory mechanisms orchestrating the sex differences in obesity and body fat distribution in humans are not well understood. Methods We searched for genetic master regulators of WHRadjBMI by employing integrative genomics approaches on human subcutaneous adipose RNA sequencing (RNA-seq) data (n ~ 1400) and WHRadjBMI GWAS data (n ~ 700,000) from the WHRadjBMI GWAS cohorts and the UK Biobank (UKB), using co-expression network, transcriptome-wide association study (TWAS), and polygenic risk score (PRS) approaches. Finally, we functionally verified our genomic results using gene knockdown experiments in a human primary cell type that is critical for adipose tissue function. Results Here, we identified an adipose gene co-expression network that contains 35 obesity GWAS genes and explains a significant amount of polygenic risk for abdominal obesity and T2D in the UKB (n = 392,551) in a sex-dependent way. We showed that this network is preserved in the adipose tissue data from the Finnish Kuopio Obesity Study and Mexican Obesity Study. The network is controlled by a novel adipose master transcription factor (TF), TBX15, a WHRadjBMI GWAS gene that regulates the network in trans. Knockdown of TBX15 in human primary preadipocytes resulted in changes in expression of 130 network genes, including the key adipose TFs, PPARG and KLF15, which were significantly impacted (FDR < 0.05), thus functionally verifying the trans regulatory effect of TBX15 on the WHRadjBMI co-expression network. Conclusions Our study discovers a novel key function for the TBX15 TF in trans regulating an adipose co-expression network of 347 adipose, mitochondrial, and metabolically important genes, including PPARG, KLF15, PPARA, ADIPOQ, and 35 obesity GWAS genes. Thus, based on our converging genomic, transcriptional, and functional evidence, we interpret the role of TBX15 to be a main transcriptional regulator in the adipose tissue and discover its importance in human abdominal obesity.

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, Nfemale=434,794; childhood BMI, N=39,620), waist-to-hip ratio (WHR, Nfemale=381,152), WHR adjusted for BMI (WHRadjBMI, Nfemale=379,501), and PCOS (Ncase=10,074, Ncontrol=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 (rg=0.47, P=2.19×10−16), childhood BMI (rg=0.31, P=6.72×10−5), and WHR (rg=0.32, P=1.34×10−10), all withstanding Bonferroni correction. A suggestive significant genetic correlation was found between PCOS and WHRadjBMI (rg=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.

Brown adipose tissue (BAT) is an emerging target against obesity and its related metabolic diseases. Wibmer et al.1 recently reported that human BAT is associated with a healthier fat distribution and improved cardiometabolic health independent of adiposity and fat distribution., Brown adipose tissue (BAT) is an emerging target against obesity and its related metabolic diseases. Wibmer et al. recently reported that human BAT is associated with a healthier fat distribution and improved cardiometabolic health independent of adiposity and fat distribution.

Purpose To quantify the complete dimensions of the retro-orbicularis oculi fat (ROOF) pad and to determine its relationship to other fat compartments of the forehead. Methods The entire forehead of 14 hemifaces of seven fresh frozen human cadavers (four female, three male) was dissected in the subcutaneous and submuscular planes. For each plane, a ruler was placed at the facial midline, and images of the dissection plane were taken at 90° and 45°. Images were analyzed for vertical height, horizontal length, the distance to midline from the point of maximal height, and area for each hemiface of the ROOF and for the entire fat compartment contiguous with the ROOF. A two-tailed t test was conducted between ROOF and ROOF plus the extended fat plane across all measurements. A Wilcoxon nonparametric signed rank test was performed to determine equivalent fat distribution of the extended fat plane over each cadaver's respective eye. Results The deep fat originating from the ROOF consistently extended laterally and superiorly in each specimen, distinctly separated via septae from the deep central, deep lateral, and the deep temporal fat compartments. The color, composition, and distribution of this contiguous deep fat did not differ phenotypically from the traditional ROOF. The extended deep fat plane possessed an average vertical height of 3.09 ± 0.68 cm, average distance to midline from point of maximal height of 3.56 ± 0.53 cm, an average horizontal length of 5.37 ± 0.82 cm, and an average area of 13.40 ± 2.69 cm. The extended deep fat demonstrated a statistically significant increase in maximal height, length, and total area compared with the ROOF. A Wilcoxon nonparametric signed rank test was nonsignificant (α = 0.01) across all measurements, demonstrating that the extended fat plane was similarly distributed over each eye. Conclusions A layer of deep fat originating from the traditionally defined ROOF extends superiorly and laterally beneath the frontalis muscle, separate from the deep lateral, deep central, and deep temporal fat pads. This is the first study to clearly demonstrate a contiguous superficial musculoaponeurotic system layer of fat extending under both the orbicularis oculi and frontalis muscles. This plane of fat is more appropriately described as the retro-orbicularis oculi and frontalis fat.

Summary: Objective: To explore the quantitative measurements and evaluation of intra-peritoneal fat distribution by MDCT and its significance in predicting intra-operative bleeding volume during D2 lymphadenectomy in gastric cancer (GC) patients. Methods: From June 2016 to September 2017, GC patients scheduled for open gastrectomy with D2 lymph-node dissection were enrolled. According to the BMI, the subjects were then classified as normal BMI(BMI

This cross-sectional study was designed to determine what role race plays in the relationship between obesity and child maltreatment (CM), which is currently unknown. One hundred fifteen participants successfully completed the study, including Whites (n=60) and Blacks (n=55) of both sexes. CM was assessed using the Childhood Trauma Questionnaire. Total fat, trunk/total fat ratio, visceral adipose tissue (VAT) and VAT/trunk ratio, were measured through Dual Energy X-ray Absorptiometry (DXA) and Corescan software estimation. A significant interaction between identifying as White and having a history of CM was found to predict body mass index (BMI) (β=5.02, p=0.025), total fat (kg) (β=9.81, p=0.036), and VAT (kg) (β=0.542, p=0.025), whereas race by itself was an insignificant predictor. An interaction between having history of physical abuse and identifying as White was found to predict BMI (β=6.993, p=0.003), total fat (β=12.683, p=0.010), and VAT (β=0.591, p=0.018). An interaction between having multiple CM subtypes and identifying as White predicts increased total fat (β=5.667, p=0.034) and VAT (β=0.335, p=0.014). Our findings indicate that the relationship between CM and obesity, measured through BMI, total body fat, and VAT, is seen in Whites but not in Blacks. Future research should investigate the nature of this racial influence to guide obesity prevention and target at-risk populations.

Aims To study the associations between fat distribution and lung functions in healthy subjects of young adults and to explore potential gender difference in these correlations. Methods A total of 2101 adult participants were recruited. Height, weight, and vital capacity index (VCI) were measured and recorded according to the national physical fitness test standard. Body compositions, including body mass index (BMI), body fat percentage (BFP), waist-to-hip ratio (WHR), fat-free mass (FFM), trunk muscle mass (TMM), fat mass (FM), visceral fat area (VFA), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT), were conducted using body composition analyzer. Data were analyzed by SPSS 20.0 software. Results We found that male participants showed significantly higher BMI, WHR, FFM, TMM, VFA, and VCI, but lower FM, BFP, and SAT in comparison with women. However, there was no significant difference in VAT between the male and female. Lung functions represented by VCI were negatively correlated with FM, VAT, SAT, and VFA for both men and women (r

The aim of this pilot study was to assess how metformin, associated with a contraceptive vaginal ring, may influence lipid and carbohydrate metabolism, fat distribution, and surrogate markers of arterial function. Among 62 patients, 25 were treated with vaginal ring plus metformin and 37 women with only vaginal ring. The effects were assessed after 6 months. The patients were submitted to evaluation of lipid and carbohydrate metabolism; extended view ultrasonographic evaluation of fat distribution; Doppler analysis of ophthalmic artery; brachial artery flow-mediated vasodilatation; oral glucose tolerance test. After 6 months, the body mass index and waist/hip ratio resulted significantly better in patients who associated metformin to vaginal ring. The fasting glucose, insulin, and glucose/insulin ratio, HOMA-IR, glucose, and insulin AUC 120 were significantly improved in metformin group. The ultrasonographic fat analysis resulted significantly better after metformin. The ophthalmic artery PI significantly improved in metformin group. The brachial artery vasodilation was better in metformin treated patients. In conclusion, metformin, associated with vaginal ring, improves the insulin and carbohydrate metabolism, reduces the body weight and android fat distribution. This, associated with the significant improvements of surrogate markers of arterial function, may be responsible of possible cardiovascular and cerebrovascular protective effects.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a global health issue and is associated with obesity and oropharyngeal crowding. Global data are limited on the effect of ethnicity and sex on these relationships. We compare associations between the apnea-hypopnea index (AHI) and these risk factors across ethnicities and sexes within sleep clinics. METHODS: This is a cross-sectional, multicenter study of patients with OSA from eight sleep centers representing the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Four distinct ethnic groups were analyzed, using a structured questionnaire: Caucasians (Australia, Iceland, Germany, United States), African Americans (United States), Asians (Taiwan), and South Americans (Brazil). Regression analyses and interaction tests were used to assess ethnic and sex differences in relationships between AHI and anthropometric measures (body mass index [BMI], neck circumference, waist circumference) or Mallampati score. RESULTS: Analyses included 1,585 individuals from four ethnic groups: Caucasian (60.6%), African American (17.5%), Asian (13.1%), and South American (8.9%). BMI was most strongly associated with AHI in South Americans (7.8% increase in AHI per 1 kg/m(2) increase in BMI; P < .0001) and most weakly in African Americans (1.9% increase in AHI per 1 kg/m(2) increase in BMI; P = .002). In Caucasians and South Americans, associations were stronger in males than females. Mallampati score differed between ethnicities but did not influence AHI differently across groups. CONCLUSIONS: We demonstrate ethnic and sex variations in associations between obesity and OSA. For similar BMI increases, South American patients show greatest AHI increases compared to African Americans. Findings highlight the importance of considering ethnicity and sex in clinical assessments of OSA risk. CITATION: Sutherland K, Keenan BT, Bittencourt L, Chen NH, Gislason T, Leinwand S, Magalang UJ, Maislin G, Mazzotti DR, McArdle N, Mindel J, Pack AI, Penzel T, Singh B, Tufik S, Schwab RJ, Cistulli PA; for the SAGIC Investigators. A global comparison of anatomic risk factors and their relationship to obstructive sleep apnea severity in clinical samples. J Clin Sleep Med. 2019;15(4):629–639.

Background Increased lower body fat is associated with reduced cardiometabolic risk. The molecular basis for depot-specific differences in gluteofemoral (GF) compared with abdominal (A) subcutaneous adipocyte function is poorly understood. In the current report, we used a combination of Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq), RNA-seq, and chromatin immunoprecipitation (ChIP)-qPCR analyses that provide evidence that depot-specific gene expression patterns are associated with differential epigenetic chromatin signatures. Methods Preadipocytes cultured from A and GF adipose tissue obtained from premenopausal apple-shaped women were used to perform transcriptome analysis by RNA-seq and assess accessible chromatin regions by ATAC-seq. We measured mRNA expression and performed ChIP-qPCR experiments for histone modifications of active (H3K4me3) and repressed chromatin (H3K27me3) regions respectively on the promoter regions of differentially expressed genes. Results RNA-seq experiments revealed an A-fat and GF-fat selective gene expression signature, with 126 genes upregulated in abdominal preadipocytes and 90 genes upregulated in GF cells. ATAC-seq identified almost 10-times more A-specific chromatin-accessible regions. Using a combined analysis of ATAC-seq and global gene expression data, we identified 74 of the 126 abdominal-specific genes (59%) with A-specific accessible chromatin sites within 200 kb of the transcription start site (TSS), including HOXA3, HOXA5, IL8, IL1b, and IL6. Interestingly, only 14 of the 90 GF-specific genes (15%) had GF-specific accessible chromatin sites within 200 kb of the corresponding TSS, including HOXC13 and HOTAIR, whereas 25 of them (28%) had abdominal-specific accessible chromatin sites. ChIP-qPCR experiments confirmed that the active H3K4me3 chromatin mark was significantly enriched at the promoter regions of HOXA5 and HOXA3 genes in abdominal preadipocytes, while H3K27me3 was less abundant relative to chromatin from GF. This is consistent with their A-fat specific gene expression pattern. Conversely, analysis of the promoter regions of the GF specific HOTAIR and HOXC13 genes exhibited high H3K4me3 and low H3K27me3 levels in GF chromatin compared to A chromatin. Conclusions Global transcriptome and open chromatin analyses of depot-specific preadipocytes identified their gene expression signature and differential open chromatin profile. Interestingly, A-fat-specific open chromatin regions can be observed in the proximity of GF-fat genes, but not vice versa. Trial registration Clinicaltrials.gov, NCT01745471. Registered 5 December 2012. Electronic supplementary material The online version of this article (10.1186/s13148-018-0582-0) contains supplementary material, which is available to authorized users.

*Sezgin, ‪Erdem Aras ( Aksaray, Yazar ), Introduction: Obesity is thought to lead to increased failure rates following total hip arthroplasty (THA). Site-specific fat distribution has been suggested to be a better indicator of risk, compared to body mass index. Fat thickness measurement methods were developed for total knee arthroplasty, however, there is limited data on the methods for THA. The aim of this study was to assess the interobserver and intraobserver reliability of a newly defined radiographic subcutaneous fat thickness ratio and investigate the correlation of this ratio with early failure following THA. Methods: 321 patients who underwent primary THA at a single institution between 2014 and 2017, with at least 1-year of follow-up and a preoperative pelvis anteroposterior x-ray radiograph were included in this study. A high hip fat thickness ratio (HFTR) was arbitrarily defined as ⩾2. Early failure was defined as revision or re-operation for any reason and death related to operation first year following THA. Results: The HFTR was shown to have excellent intraobserver and interobserver reliability. High HFTR was associated with higher risk of early failure following THA (odds ratio 3.8, [95% confidence interval, 1.2–12.1], p < 0.05). The same association persisted when HFTR was analysed as a continuous variable (p < 0.01) and in multivariate analysis (p < 0.05). Conclusions: HFTR can be used to assess periarticular soft tissue distribution and may be regarded as a useful and reproducible tool for assessing risk of early failure following THA.

Context Subcutaneous adipose tissue (SAT) is not homogeneous, as the fascia scarpa separates the deep SAT (dSAT) from the superficial SAT (sSAT). Objective The aim of this study is to evaluate the sex-specific associations of sSAT and dSAT with hepatic steatosis and metabolic syndrome in overweight individuals. Methods We recruited 285 individuals with a body mass index (BMI) greater than or equal to 27 and aged 55 to 81 years. Abdominal magnetic resonance imaging was performed around level L4 to L5 to measure visceral adipose tissue (VAT), dSAT, and sSAT volumes. The amount of hepatic fat was quantified by MR spectroscopy. Results Men had significantly higher volumes of VAT (122.6 cm3 vs 98.7 cm3, P Conclusion In men, dSAT is associated with hepatic steatosis and adverse metabolic traits, such as lower HDL cholesterol levels, whereas in women with obesity sSAT shows a beneficial relation with respect to hepatic fat content.

Context The relation between the menopause transition (MT) and changes in regional fat distribution is uncertain. Objective To determine whether the MT is associated with the development of central adiposity. Design Longitudinal analysis from the Study of Women’s Health Across the Nation, spanning 1996-2013 (median follow-up 11.8 years). Setting Community-based. Participants 380 women with regional body composition measures by dual energy X-ray absorptiometry. Mean baseline age was 45.7 years; racial/ethnic composition was 16% Black, 41% Japanese and 43% White. Outcomes Changes in android, gynoid and visceral fat and waist and hip circumferences. Results Android fat increased by 1.21% per year (py) and 5.54% py during premenopause and the MT, respectively (each P Conclusions The MT is associated with the development of central adiposity. Waist or hip circumferences are less sensitive to changes in fat distribution.

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.

Rationale & Objectives Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. Study Design Prospective cohort study. Setting & Participants Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). Predictors VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). Outcomes Markers of inflammation (interleukin 1β [IL-1β], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). Analytical Approach Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. Results Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2 ± 14.6 (SD) mL/min/1.73 m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. Limitations Lack of longitudinal data and dietary details. Conclusions Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.

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.

Neck fat distribution plays an important role in aging, yet how fat distribution changes with age is largely unknown. This study used volumetric computed tomography in live patients to characterize neck fat volume and distribution in young and elderly women.A retrospective analysis was conducted of head and neck computed tomographic angiographs of 20 young (aged 20 to 35 years) and 20 old (aged 65 to 89 years) women. Fat volume in the supraplatysmal and subplatysmal planes was quantified. Distribution of fat volume was assessed by dividing each supraplatysmal and subplatysmal compartment into upper, middle, and lower thirds.Total supraplatysmal fat volume was greater than subplatysmal in all patients. Young patients had more total supraplatysmal fat than old patients (p0.0001). No difference was found between age groups in subplatysmal fat (p0.05). No difference was found between upper/middle/lower third supraplatysmal fat volumes in young patients. When comparing supraplatysmal thirds within the elderly population, the middle third fat volume (28.58 ± 20.01 cm3) was greater than both upper (18.93 ± 10.35 cm3) and lower thirds (15.46 ± 11.57 cm3) (p0.01).This study suggests that total supraplatysmal fat volume decreases with age. Older patients had more fat volume in the upper and middle thirds compared with the lower third of the supraplatysmal fat compartment, whereas young patients had more evenly distributed fat. These results suggest that fat deposition and redistribution in the neck occur with age and may be a contributing factor to the obtuse cervicomandibular angle of the elderly.

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids., The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

OBJECTIVES To investigate associations between androgens (testosterone, dehydroepiandrosterone sulphate [DHEAS] and androstenedione), adiposity, fat distribution and insulin resistance (IR) during childhood and adolescence. METHODS Three hundred and seven children (170 [55.4%] boys; 137 [44.6%] girls) recruited at age 5 and studied annually until age 16: androgens (liquid chromatography tandem-mass spectrometry), anthropometry, body composition (dual-energy x-ray absorptiometry) and IR (homeostasis model assessment). RESULTS Early adiposity was associated with earlier detection of androstenedione in both sexes, and DHEAS in boys. At puberty, higher androgen levels were associated with favourable metabolic changes in boys, but adverse metabolic effects in girls. In boys, higher free testosterone (FT) was associated with lower body fat and android/gynoid fat ratio (AGR) (both P

Objective This study aimed to investigate the relationships among physical activity (PA), diet quality, body composition, and fat distribution in a representative sample of US adults. Methods A cross-sectional analysis was conducted using publicly accessible data from the 2011 to 2016 National Health and Nutrition Examination Survey and the Food Patterns Equivalents Database (n = 7,423). Variables from the data sets were analyzed for this study, including PA, two 24-hour dietary recalls, and dual-energy x-ray absorptiometry outputs. Results For men, PA and diet quality were inversely associated with the percentage of body fat (β = -0.0042, 95% CI: -0.0084 to -0.0001; β = -0.28, 95% CI: -0.42 to -0.14) and fat mass index (β = -0.0125, 95% CI: -0.0209 to -0.0041; β = -0.56, 95% CI: -0.81 to -0.32); meeting the PA recommendation and having good diet quality provided an additive effect on body fat. A similar pattern was observed in women. Additionally, diet quality was inversely associated with all fat distribution measures in both sexes, whereas PA was positively associated with lean mass measures in men only. Conclusions Increased PA and/or better diet quality were associated with reduced body fat, a healthier fat distribution, and increased lean mass. Further research examining how changes in PA or diet quality influence body composition and fat distribution in adults is warranted.

Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two independent GWAS signals at RSPO3, which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase RSPO3 expression in subcutaneous adipocytes. These variants are also associated with reduced lower-body fat, enlarged gluteal adipocytes and insulin resistance. Based on human cellular studies RSPO3 may limit gluteofemoral adipose tissue (AT) expansion by suppressing adipogenesis and increasing gluteal adipocyte susceptibility to apoptosis. RSPO3 may also promote upper-body fat distribution by stimulating abdominal adipose progenitor (AP) proliferation. The distinct biological responses elicited by RSPO3 in abdominal versus gluteal APs in vitro are associated with differential changes in WNT signalling. Zebrafish carrying a nonsense rspo3 mutation display altered fat distribution. Our study identifies RSPO3 as an important determinant of peripheral AT storage capacity., Genetic variants at the RSPO3 locus are associated with waist-to-hip ratio (adjusted for BMI). Here, Loh et al. describe two independent RSPO3 signals that associate with body fat distribution, perform fine-mapping and explore the function of RSPO3 in human adipocyte biology and body fat distribution in zebrafish

ObjectivesThis study was an attempt to investigate the variation trend of body composition with ageing and explore the association between regional body composition and bone mineral density (BMD).DesignCross-sectional study.Setting and participantsA total of 5749 healthy adults aged 20–95 years was recruited from 2004 to 2017.Primary outcome measuresWhole-body lean mass (LM), fat mass (FM), android FM, gynoid FM, appendicular lean mass (ALM) and BMD in the lumbar spine, femoral neck and total hip were obtained by dual-energy X-ray absorptiometry (DXA). The android/gynoid fat mass ratio (A/G FMR) based on DXA scan was calculated as an indicator of adipose distribution. Pearson correlation and multiple linear regression analyses were used to determine the associations between body composition, adipose distribution, and BMD of each skeletal site.ResultsWhole-body FM, percentage of whole-body FM, Android FM and A/G FMR consistently increased with age in both genders, especially in women, and ALM began to decrease in the fifth decade for both men and women. In multivariable linear regression models with age, body mass index, A/G FMR and ALM as predictor variables, ALM was associated with the most BMD variance of all skeletal sites in men (standard β ranged from 0.207 to 0.405, pConclusionsIn this large cohort of Chinese adults, ALM had a strong positive association with BMD in both genders. A/G FMR as an indicator of central adipose accumulation was inversely associated with BMD in women but not in men.

IntroductionRegional fat distribution strongly relates to metabolic comorbidities. We identified the DNA repair genes H2AX and HMGB1 to be differentially expressed between human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) depots. As increased DNA damage is linked to metabolic disease, we here sought to analyze whether depot-specific H2AX and HMGB1 expression is related to anthropometric and metabolic profiles of obesity. We further tested for different H2AX mRNA regulatory mechanisms by analyzing promoter DNA methylation and genotyped rs7350 in the H2AX locus.Research design and methodsGene expression (OVAT n=48; SAT n=55) and DNA promoter methylation data (OVAT and SAT n=77) were extracted from an existing dataset as described elsewhere. Genotype data for the 3’untranslated region (3’UTR) H2AX variant rs7350 were generated by using the TaqMan genotyping system in 243 subjects of the same cohort. Statistical analyses were done using SPSS statistics software 24 and GraphPad Prism 6.ResultsWe identified H2AX being higher (p=0.002) and HMGB1 being less expressed (p=0.0001) in OVAT compared with SAT. Further, we observed positive interdepot correlations of OVAT and SAT for both HMGB1 (p=1×10–6) and H2AX mRNA levels (p=0.024). Depot-specific associations were observed for both genes’ methylation levels with either high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides and/or with OVAT/SAT-ratio (all pHMGB1 expression level (p=0.030).ConclusionOur results suggest a fat depot-specific regulation of H2AX and HMGB1 potentially mediated by both DNA methylation and genetic variation. Rs7350, DNA methylation and/or mRNA levels of H2AX and HMGB1 are related to lipid parameters. Further studies are warranted to evaluate the functional role of the DNA repair genes H2AX and HMGB1 in obesity and fat distribution.

Background Children born small for gestational age (SGA) with catch-up growth are at high risk for developing obesity; however, the characteristics of body composition, especially fat distribution, before and after growth hormone (GH) treatment in SGA children without catch-up growth remains largely unknown. Methods Anthropometric characteristics, body composition by dual-energy X-ray absorption, and fat distribution by computed tomography at the umbilical level were examined in 27 prepubertal short-stature children born SGA before and 1 year after GH treatment. Results Before GH treatment, short-stature SGA children had lean phenotypes, and both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were significantly lower than the age- and sex-matched Japanese reference values. Growth hormone treatment significantly increased height standard deviation scores (SDS), without affecting body mass index SDS. Percentage fat mass decreased with GH treatment; however, fat mass was not altered. Both VAT and SAT were significantly lower than the reference values after GH treatment. The ratio of VAT over SAT significantly increased by GH treatment. Conclusions Both VAT and SAT were within or below the age- and sex-matched Japanese reference values in short-stature children born SGA before and after GH treatment, indicating that GH treatment may not have unfavorable effects on adiposity in short-stature children born SGA, although it may alter fat distribution.

Although obesity is considered osteoprotective, the effects of body fat and fat distribution on bone tissue after adjusting for the effects of body weight remain uncertain. This study evaluated the relationships between fat mass, fat distribution, and bone mineral status beyond its weight-bearing effect. We recruited 466 children aged 6&ndash, 10 years in China. Dual-energy X-ray absorptiometry was used to determine the bone mineral density (BMD) and bone mineral content (BMC) in the total body and total body less head (TBLH), as well as the fat mass (FM) and percentage fat mass (%FM) of the total and segmental body. Weight-adjusted measures of FM and %FM were derived using the residual method. After adjusting for the effects of covariates, we observed statistically significant, dose-dependent negative relationships between the TBLH&middot, BMD/BMC and various weight-adjusted measures of body fat (p for trend: &lt, 0.001&ndash, 0.038). For each standard deviation increment in the weight-adjusted total body, TBLH, trunk and limbs, the size-adjusted BMC decreased approximately 9.44, 9.28, 8.13, and 6.65 g in boys, respectively, and by approximately 13.74, 13.71, 7.84, and 12.95 g in girls, respectively. Significant inverse associations between FM accumulation in the total body and most body parts with the BMD/BMC were observed in both boys and girls after adjusting for weight and potential confounders.

Background Altered fat distribution and chronic inflammation are found in both persons living with HIV (PLWH) and persons with diabetes mellitus type 2 (DM2) and are known risk factors for cardiovascular diseases (CVD). We aimed to investigate if a synergistic effect of HIV infection and DM2 was found on fat distribution and inflammation. Methods A cross-sectional study was performed including PLWH with HIV RNA α) and soluble CD14 (sCD14) was measured using snap-frozen plasma. Results HIV + DM2+ and HIV + DM2- had comparable trunk/limb fat ratio. In contrast, HIV + DM2+ had a higher trunk/ limb fat ratio than controls with DM2 and healthy controls (p = 0.013 and p p = 0.254). A lower concentration of plasma adiponectin and higher concentration of IL-6 was found in HIV + DM2+ than in HIV + DM2-(p = 0.037 and p = 0.039) and in healthy controls (p = 0.001 and p = 0.012). In contrast, plasma adiponectin and IL-6 concentrations were comparable in HIV + DM2+ and controls with DM2 (p = 0.345 and p = 0.825). Concentration of sCD14 was comparable in HIV + DM2+ and HIV + DM2–(p = 0.850), but elevated in HIV + DM2+ compared to controls with DM2 (p p = 0.007). No statistical interactions were found between HIV infection and DM2 for any of the depending variables. Conclusion A synergistic effect of HIV and DM2 was not found for any of the outcomes. However, HIV + DM2+ had features related to both HIV infection and DM2 with a high trunk/limb ratio, high trunk fat mass, low concentration of plasma adiponectin and elevated concentrations of IL-6 and sCD14. This could contribute to elevated risk of CVD.