scholarly journals Shared Genetic Loci For Body Fat Storage And Adipocyte Lipolysis In Humans

2021 ◽  
Author(s):  
Agné Kulyté ◽  
Veroniqa Lundbäck ◽  
Peter Arner ◽  
Rona J. Strawbridge ◽  
Ingrid Dahlman
Keyword(s):  
Candidate Genes ◽  
Body Fat ◽  
Genetic Variants ◽  
Association Studies ◽  
Fat Distribution ◽  
Functional Evaluation ◽  
Genome Wide Association Studies ◽  
Fat Storage ◽  
Total Body Fat ◽  
Total Body

Abstract Background. Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis.Methods. We utilized data from the recent GWAS of spontaneous and isoprenaline-stimulated lipolysis in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort. GENiAL consists of 939 participants who have undergone abdominal subcutaneous adipose biopsy for the determination of spontaneous and isoprenaline-stimulated lipolysis in adipocytes. Results. We report 11 BMI and 15 WHRadjBMI loci with SNPs displaying nominal association with lipolysis and allele-dependent gene expression in adipose tissue according to in silico analysis. Functional evaluation of candidate genes in these loci by small interfering RNAs (siRNA)-mediated knock-down in adipose-derived stem cells identified ZNF436 and NUP85 as intrinsic regulators of lipolysis consistent with the associations observed in the clinical cohorts. Furthermore, candidate genes in another BMI-locus (STX17) and two more WHRadjBMI loci (NID2, GGA3, GRB2) control lipolysis alone, or in conjunction with lipid storage, and may hereby be involved in genetic control of body fat.Conclusions. The findings expand our understanding of how genetic variants mediate their impact on the complex traits of fat storage and distribution.

scholarly journals Genetics of Body Fat Distribution: Comparative Analyses in Populations with European, Asian and African Ancestries

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 841
Author(s):  
Chang Sun ◽  
Peter Kovacs ◽  
Esther Guiu-Jurado
Keyword(s):  
Candidate Genes ◽  
Body Fat ◽  
Current Knowledge ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association Studies ◽  
Metabolic Complications ◽  
Asian Populations ◽  
European Populations

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.

Abstract 22: Influence of Smoking and Sex on Genetic Associations of Body Fat Distribution: The Giant (Genetic Investigation of ANthropometric Traits) Consortium

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Kristin L Young ◽  
David Hadley ◽  
Anne Justice ◽  
Thomas Winkler ◽  
Misa Graff ◽  
...  
Keyword(s):  
Body Fat ◽  
Genetic Variants ◽  
Fixed Effects ◽  
Smoking Status ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Main Effects

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.

scholarly journals Total body fat, abdominal fat, body fat distribution and surrogate markers for health related to adipocyte fatty acid-binding protein (FABP4) in children

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Magnus Dencker ◽  
Anton Danielson ◽  
Magnus K. Karlsson ◽  
Per Wollmer ◽  
Lars B. Andersen ◽  
...  
Keyword(s):  
Body Fat ◽  
Fatty Acid Binding Protein ◽  
Fat Body ◽  
Community Sample ◽  
Fat Distribution ◽  
Abdominal Fat ◽  
Body Fat Distribution ◽  
Fatty Acid Binding ◽  
Total Body Fat ◽  
Total Body

AbstractBackground:The aim of the study was to assess possible relationships between adipocyte fatty acid-binding protein (FABP4) and total body fat (TBF), abdominal fat, body fat distribution, aerobic fitness, blood pressure, cardiac dimensions and the increase in body fat over 2 years in a community sample of children.Methods:A cross-sectional study was used in a community sample of 170 (92 boys and 78 girls) children aged 8–11 years. TBF and abdominal fat (AFM) were measured by dual-energy X-ray absorptiometry (DXA). TBF was also expressed as percentage of total body mass (BF%), and body fat distribution was calculated as AFM/TBF. Maximal oxygen uptake (VOResults:Partial correlations, with adjustment for sex, between FABP4 vs. ln TBF, ln BF%, ln AFM, AFM/TBF and VOConclusions:Findings from this community-based cohort of young children show that increased body fat and abdominal fat, more abdominal body fat distribution, low fitness, more LVM and increased LA, increased SBP and PP were all associated with increased levels of FABP4. Increase in TBF and abdominal fat over 2 years were also associated with increased levels of FABP4.

scholarly journals Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

2018 ◽  
Vol 28 (1) ◽  
pp. 166-174 ◽  
Author(s):  
Sara L Pulit ◽  
Charli Stoneman ◽  
Andrew P Morris ◽  
Andrew R Wood ◽  
Craig A Glastonbury ◽  
...  
Keyword(s):  
Body Fat ◽  
Association Studies ◽  
Meta Analysis ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

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.

Dietary fat composition, total body fat and regional body fat distribution in two Caucasian populations of middle-aged and older adult women

2017 ◽  
Vol 36 (5) ◽  
pp. 1411-1419 ◽  
Author(s):  
Taulant Muka ◽  
Lauren C. Blekkenhorst ◽  
Joshua R. Lewis ◽  
Richar L. Prince ◽  
Nicole S. Erler ◽  
...  
Keyword(s):  
Older Adult ◽  
Body Fat ◽  
Dietary Fat ◽  
Fat Distribution ◽  
Adult Women ◽  
Middle Aged ◽  
Total Body Fat ◽  
Fat Composition ◽  
Regional Body Fat ◽  
Total Body

scholarly journals Fetal alleles predisposing to metabolically favourable adiposity are associated with higher birth weight

2020 ◽  
Author(s):  
WD Thompson ◽  
RN Beaumont ◽  
A Kuang ◽  
NM Warrington ◽  
Y Ji ◽  
...  
Keyword(s):  
Birth Weight ◽  
Cord Blood ◽  
Body Fat ◽  
Genetic Predisposition ◽  
Genetic Variants ◽  
Fat Distribution ◽  
Genome Wide Association Studies ◽  
Genetic Score ◽  
Maternal Genotype ◽  
Adult Body

AbstractBackgroundHigher birth weight is associated with higher adult body mass index (BMI). If genetic variants can be identified with alleles that predispose to both greater fetal growth and to greater adult adiposity, such shared genetic effects might indicate biological processes important in the early patterning of adiposity. However, variants identified in genome-wide association studies of adult BMI have overall been only weakly associated with birth weight. Genetic variants have recently been identified where one allele is associated with higher adult body fat percentage, but lower risk of metabolic disease, likely due to a favourable body fat distribution. The effect of these adult metabolically favourable adiposity alleles on an individual’s own birth weight is unknown.AimWe aimed to test the effect on birth weight of a fetal genetic predisposition to higher metabolically favourable adult adiposity and to compare this with the effects of a fetal genetic predisposition to higher adult BMI. We also aimed to examine the effects of a genetic predisposition to higher metabolically favourable adult adiposity or BMI on other birth anthropometric traits (length, ponderal index, head circumference and skinfold thickness) and on cord-blood insulin, leptin and adiponectin.MethodsWe used published GWAS data from up to 406,063 individuals to estimate the fetal effects on birth weight of alleles that are robustly associated with higher metabolically favourable adult adiposity or BMI. We additionally used 9,350 mother-child pairs from four cohorts to test the effects of the same alleles on other birth anthropometric traits and cord-blood markers. In all analyses, we adjusted for potential confounding due to the maternal genotype. We used inverse-variance weighted meta-analyses to combine summary data across SNPs.ResultsFetal genetic predisposition to higher metabolically favourable adult adiposity was associated with higher birth weight (10 grams (95% CI: 7 to 13) higher mean birth weight per 1 SD pooled “genetic score”). Fetal genetic predisposition to higher adult BMI was also associated with higher birth weight, but with a smaller magnitude of effect (4 grams (95% CI: 0 to 8) higher mean birth weight per 1 SD pooled “genetic score”) and with higher heterogeneity across SNPs. Effects on other birth anthropometric outcomes were consistent with the effect on birth weight but with wider confidence intervals. There was no strong evidence for an effect on cord-blood markers.ConclusionsSome genetic variants previously linked to adult adiposity influence birth weight. Alleles that predispose to higher metabolically favourable adult adiposity collectively have a stronger effect on birth weight than those predisposing to higher BMI. This suggests that the early accumulation of a metabolically favourable fat distribution might underlie part of the observed association between higher birth weight and higher adult BMI. Larger samples are needed to clarify the effects on other birth anthropometric measures and cord-blood markers.

scholarly journals Genome-Wide Association Study of Body Fat Distribution identifies Novel Adiposity Loci and Sex-Specific Genetic Effects

2017 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Torgny Karlsson ◽  
Weronica E Ek ◽  
Åsa Johansson
Keyword(s):  
Body Fat ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

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.

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