scholarly journals Sexual dimorphisms in genetic loci linked to body fat distribution

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Sara L. Pulit ◽  
Tugce Karaderi ◽  
Cecilia M. Lindgren

Obesity is a chronic condition associated with increased morbidity and mortality and is a risk factor for a number of other diseases including type 2 diabetes and cardiovascular disease. Obesity confers an enormous, costly burden on both individuals and public health more broadly. Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes. Body fat distribution is distinct from overall obesity in measurement, but studies of body fat distribution can yield insights into the risk factors for and causes of overall obesity. Sexual dimorphism in body fat distribution is present throughout life. Though sexual dimorphism is subtle in early stages of life, it is attenuated in puberty and during menopause. This phenomenon could be, at least in part, due to the influence of sex hormones on the trait. Findings from recent large genome-wide association studies (GWAS) for various measures of body fat distribution (including waist-to-hip ratio, hip or waist circumference, trunk fat percentage and the ratio of android and gynoid fat percentage) emphasize the strong sexual dimorphism in the genetic regulation of fat distribution traits. Importantly, sexual dimorphism is not observed for overall obesity (as assessed by body mass index or total fat percentage). Notably, the genetic loci associated with body fat distribution, which show sexual dimorphism, are located near genes that are expressed in adipose tissues and/or adipose cells. Considering the epidemiological and genetic evidence, sexual dimorphism is a prominent feature of body fat distribution. Research that specifically focuses on sexual dimorphism in fat distribution can provide novel insights into human physiology and into the development of obesity and its comorbidities, as well as yield biological clues that will aid in the improvement of disease prevention and treatment.

2018 ◽  
Vol 28 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Sara L Pulit ◽  
Charli Stoneman ◽  
Andrew P Morris ◽  
Andrew R Wood ◽  
Craig A Glastonbury ◽  
...  

Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.


2017 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Torgny Karlsson ◽  
Weronica E Ek ◽  
Åsa Johansson

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested as more pathogenic compared to fat stored in other compartments of the body. In this study, we performed genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. A total of 97 loci, were identified to be associated with body fat distribution, 40 of which have not previously been associated with an anthropometric trait. A high degree of sex-heterogeneity was observed and associations were primarily observed in females, particularly for distribution of fat to the legs or trunk. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues a well as several enzymatically active members of the ADAMTS family of metalloproteinases, which are involved in extracellular matrix maintenance and remodeling.


Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 841
Author(s):  
Chang Sun ◽  
Peter Kovacs ◽  
Esther Guiu-Jurado

Preferential fat accumulation in visceral vs. subcutaneous depots makes obese individuals more prone to metabolic complications. Body fat distribution (FD) is regulated by genetics. FD patterns vary across ethnic groups independent of obesity. Asians have more and Africans have less visceral fat compared with Europeans. Consequently, Asians tend to be more susceptible to type 2 diabetes even with lower BMIs when compared with Europeans. To date, genome-wide association studies (GWAS) have identified more than 460 loci related to FD traits. However, the majority of these data were generated in European populations. In this review, we aimed to summarize recent advances in FD genetics with a focus on comparisons between European and non-European populations (Asians and Africans). We therefore not only compared FD-related susceptibility loci identified in three ethnicities but also discussed whether known genetic variants might explain the FD pattern heterogeneity across different ancestries. Moreover, we describe several novel candidate genes potentially regulating FD, including NID2, HECTD4 and GNAS, identified in studies with Asian populations. It is of note that in agreement with current knowledge, most of the proposed FD candidate genes found in Asians belong to the group of developmental genes.


2021 ◽  
Vol 10 (23) ◽  
pp. 5713
Author(s):  
Dolores Escrivá ◽  
Jordi Caplliure-Llopis ◽  
Inmaculada Benet ◽  
Gonzalo Mariscal ◽  
Juan Vicente Mampel ◽  
...  

The purpose of this study was to analyze the adiposity profile and the body fat distribution in 56 sub-elite female rugby union players involved in the Spanish National Women’s Rugby Union Championships. The participants included in this study, which was the first to analyze sub-elite players, show thinner skinfolds, lower fat mass, and lesser fat percentage than previously reported for elite female rugby union players. Forwards were heavier and had higher body mass index (BMI) and fat mass, thicker skinfolds, and higher fat percentage than back players. Forwards also possessed significantly greater total fat-free mass than backs. All these differences were applicable only to players under 25 years of age. A negative correlation between age and both abdominal and lower extremity fat was found in forward players but not in the backs. Both Yuhasz and Faulkner equations tended to underestimate fat percentage in comparison to Reilly equation. Although Yuhasz equation provided higher systematic error, random error was lower in comparison to Faulkner equation. This study shows the relevance of analyzing and monitoring adiposity in female rugby union players to optimize adaptation to the sports requirements of different playing positions and age.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristin L Young ◽  
David Hadley ◽  
Anne Justice ◽  
Thomas Winkler ◽  
Misa Graff ◽  
...  

Visceral fat and smoking are important risk factors for CVD and other long-term poor health outcomes. Central adiposity is frequently assessed in population studies using waist-to-hip ratio adjusted for BMI (WHRadjBMI). Genome-wide association studies (GWAS) have discovered loci that influence WHRadjBMI, sometimes with sex-specific effects. However, we do not know whether and how smoking behavior influences the association between genetic variants and WHRadjBMI. Our study investigates the influence of smoking and genetic variants on WHRadjBMI, with particular consideration for differential effects by sex. Forty-one GIANT GWAS (108,397 participants) were used to investigate the influence of smoking on SNP WHRadjBMI associations using sex-stratified models considering SNP main effects adjusted for smoking status, and SNP main effects stratified by smoking status. Results from each study were meta-analyzed using an inverse-variance weighted fixed-effects model for men and women separately as well as combined. A total of 19 SNPs reached genome-wide significance (p<5x10-8) having adjusted the SNP effect for smoking across strata (women, men, and combined), including 11 previously reported WHRadjBMI loci. For known WHRadjBMI loci, the influence of smoking varied by sex. In women, four known WHRadjBMI SNPs (TBX15, DNM3, RSPO3, and ADAMTS9) had a greater effect in smokers vs. nonsmokers (TBX15: β(SE) = 0.0506 (0.014), p = 3.84x10-4) vs. β(SE) = 0.0382 (0.0072), p = 1.14x10-7). Three of these (TBX15, DNM3, RSPO3) have been previously associated with tobacco use disorder (TUD). In men, three known WHRadjBMI loci (ADAMTS9, DNM3, ZNRF3) had a greater effect among smokers vs nonsmokers (ZNRF3: β(SE) = 0.0365 (0.0148), p = 1.37x10-2) vs β(SE) = 0.0192 (0.0088), p = 12.87x10-2). Eight of our 19 top SNPs have not been previously associated with WHRadjBMI (within 500 kb). Of these eight loci, distinct patterns of association by smoking and sex were again noted. In addition, one locus (ABCA1) has been previously associated with TUD. In addition to identifying novel loci associated with body fat distribution, these findings underscore the importance of considering the effect of smoking when investigating the genetics of obesity related phenotypes and emphasize the need to consider sex separately when studying the effects of smoking on body fat distribution.


2018 ◽  
Author(s):  
Sara L. Pulit ◽  
Charli Stoneman ◽  
Andrew P. Morris ◽  
Andrew R. Wood ◽  
Craig A. Glastonbury ◽  
...  

AbstractOne in four adults worldwide are either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, is most informative for predicting risk of obesity sequellae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio adjusted for BMI (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.


2018 ◽  
Vol 104 (3) ◽  
pp. 900-905 ◽  
Author(s):  
Juan Tiraboschi ◽  
Antonio Navarro-Alcaraz ◽  
Dolors Giralt ◽  
Carmen Gomez-Vaquero ◽  
Maria Saumoy ◽  
...  

Abstract Objectives To describe the changes in body fat distribution (BFD) occurring over 60 months in a group of antiretroviral therapy (ART)-naive individuals starting different antiretroviral regimens. Methods A prospective ongoing fat change assessment including clinical evaluation and dual X-ray absorptiometry scan is being conducted in all consecutive patients initiating ART from January 2008. Arm, leg, trunk, and total fat as well as fat mass ratio were determined. Results A total of 146 patients were included (80% male, 40% MSM). Mean age was 44 years, HIV-1 RNA was 4.98 log10 copies/mL, and CD4 count was 254 cells/μL. The most common initial antiretroviral combination included non-nucleoside reverse transcription inhibitor (NNRTI) drugs followed by protease inhibitor (PI) and integrase strand transfer inhibitor (INSTI)-based regimens. At month 36, an increase was seen in the body mass index (BMI), total fat, trunk fat, and limb fat. The fat mass ratio (FMR) also showed a significant increase in both men and women (P = 0.001). In patients receiving NNRTI- or INSTI-based regimens (but not PIs), there was a marginal but statistically significant increase in the FMR (0.10 and 0.07, respectively; P = 0.01). Sixty-two subjects completed 60 months of follow-up. FMR showed a significant increase even in the PI group at this time point (P &lt; 0.03). Conclusions We observed a significant increase in the fat and lean body mass in all compartments and treatment groups over 36 and 60 months. Clinically irrelevant differences were found in fat distribution regardless of the treatment group and baseline characteristics. The data suggest that current antiretroviral regimens have little impact on BFD during the first years of treatment.


BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e022465
Author(s):  
Chen Wei ◽  
Sunyue Ye ◽  
Jessica Ruolin Sheng ◽  
Xiaoguang Ma ◽  
Yuan Ru ◽  
...  

IntroductionPrevious studies have showed association between smoking and central fat distribution. However, the impact of smoking on whole body fat distribution, particularly peripheral fat distribution remains unclear.MethodsNicotine dependence was assessed in a total of 1264 male adults aged 18–80 years using the Fagerström Test for Nicotine Dependence (FTND). Smoking status was categorised as non-smokers, former and current smokers with very low, low/moderate, or high FTND scores. Body fat distribution was determined using the dual energy X-ray absorptiometry and anthropometric measurements. Multivariable linear regression models were applied to examine the adjusted associations between body fat distribution and smoking in all participants, and its association with FTND scores in the current smokers.ResultsGreater waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), trunk fat percentage (%TF), android fat percentage (%AF) and android-to-gynoid fat mass ratio (AOI); but lower legs fat percentage (%LegF), limb fat percentage (%LimbF) and gynoid fat percentage (%GF) were found in current smokers with high FTND scores compared with non-smokers. In current smokers aged 60 years or older, FTND scores had positive associations with WC, WHR, WHtR, %TF, %AF and AOI, and negative associations with %LegF, %LimbF and %GF.ConclusionsNicotine dependence was positively associated with central fat distribution and negatively associated with peripheral fat distribution in Chinese male adults, particularly in those older or heavy smokers, and these associations were independent from body mass index, which might be due to long exposure to smoking.


2015 ◽  
Vol 113 (S2) ◽  
pp. S11-S18 ◽  
Author(s):  
Yaakov Henkin ◽  
Julia Kovsan ◽  
Yftach Gepner ◽  
Iris Shai

Body fat distribution, especially visceral fat accumulation, may contribute more than total fat mass per se to the development of metabolic and cardiovascular disorders. Early prevention highly improves health outcomes later in life, especially when considering such cumulative conditions as atherosclerosis. However, as these processes emerge to be partly reversible, dietary and lifestyle interventions at any age and health condition are greatly beneficial. Given the worldwide abundance of metabolic and cardiovascular disorders, the identification and implementation of strategies for preventing or reducing the accumulation of morbid fat tissues is of great importance for preventing and regressing atherosclerosis. This review focuses on dietary strategies and specific food components that were demonstrated to alter body fat distribution and regression of atherosclerosis. Different properties of various adipose depots (superficial subcutaneous, deep subcutaneous and visceral fat depots) and their contribution to metabolic and cardiovascular disorders are briefly discussed. Visceral obesity and atherosclerosis should be approached as modifiable rather than ineluctable conditions.


Sign in / Sign up

Export Citation Format

Share Document