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Derek Klarin - One of the best experts on this subject based on the ideXlab platform.

  • dna sequence variation in acvr1c encoding the activin receptor like kinase 7 influences Body Fat Distribution and protects against type 2 diabetes
    Diabetes, 2019
    Co-Authors: Connor A Emdin, Amit Khera, Krishna G Aragam, Mary E Haas, Mark Chaffin, Derek Klarin
    Abstract:

    A genetic predisposition to higher waist-to-hip ratio adjusted for Body mass index (WHRadjBMI), a measure of Body Fat Distribution, associates with increased risk for type 2 diabetes. We conducted an exome-wide association study of coding variation in UK Biobank (405569 individuals) to identify variants that lower WHRadjBMI and protect against type 2 diabetes. We identified four variants in the gene ACVR1C, encoding the activin-receptor like kinase 7 receptor expressed on adipocytes and pancreatic beta cells, which independently associated with reduced WHRadjBMI: Asn150His (-0.09 standard deviations, p=3.4*10-17), Ile195Thr (-0.15 SD, p=1.0*10-9), Ile482Val (-0.019 SD, p=1.6*10-5) and rs72927479 (-0.035 SD, p=2.6*10-12). Carriers of these variants exhibited reduced percent abdominal Fat in dual energy X-ray imaging. Pooling across all four variants, a 0.2 SD decrease in WHRadjBMI through ACVR1C was associated with a 30% lower risk of type 2 diabetes (OR 0.70, CI 0.63, 0.77; p = 5.6*10-13). In an analysis of exome sequences from 55516 individuals, carriers of predicted damaging variants in ACVR1C were at 54% lower risk of type 2 diabetes (OR 0.46 CI 0.27, 0.81; p=0.006). These findings indicate that variants predicted to lead to loss of ACVR1C gene function influence Body Fat Distribution and protect from type 2 diabetes.

  • dna sequence variation in acvr1c encoding the activin receptor like kinase 7 influences Body Fat Distribution and protects against type 2 diabetes
    Diabetes, 2019
    Co-Authors: Connor A Emdin, Amit Khera, Krishna G Aragam, Mary E Haas, Mark Chaffin, Derek Klarin
    Abstract:

    A genetic predisposition to higher waist-to-hip ratio adjusted for BMI (WHRadjBMI), a measure of Body Fat Distribution, associates with increased risk for type 2 diabetes. We conducted an exome-wide association study of coding variation in UK Biobank (405,569 individuals) to identify variants that lower WHRadjBMI and protect against type 2 diabetes. We identified four variants in the gene ACVR1C (encoding the activin receptor-like kinase 7 receptor expressed on adipocytes and pancreatic β-cells), which independently associated with reduced WHRadjBMI: Asn150His (-0.09 SD, P = 3.4 × 10-17), Ile195Thr (-0.15 SD, P = 1.0 × 10-9), Ile482Val (-0.019 SD, P = 1.6 × 10-5), and rs72927479 (-0.035 SD, P = 2.6 × 10-12). Carriers of these variants exhibited reduced percent abdominal Fat in DEXA imaging. Pooling across all four variants, a 0.2 SD decrease in WHRadjBMI through ACVR1C was associated with a 30% lower risk of type 2 diabetes (odds ratio [OR] 0.70, 95% CI 0.63, 0.77; P = 5.6 × 10-13). In an analysis of exome sequences from 55,516 individuals, carriers of predicted damaging variants in ACVR1C were at 54% lower risk of type 2 diabetes (OR 0.46, 95% CI 0.27, 0.81; P = 0.006). These findings indicate that variants predicted to lead to loss of ACVR1C gene function influence Body Fat Distribution and protect from type 2 diabetes.

V W V Jaddoe - One of the best experts on this subject based on the ideXlab platform.

  • Body Fat Distribution overweight and cardiac structures in school age children a population based cardiac magnetic resonance imaging study
    Journal of the American Heart Association, 2020
    Co-Authors: Liza Toemen, A A Roest, G Jelic, J F Felix, W A Helbing, R Gaillard, Susana Santos, Aad Van Der Lugt, V W V Jaddoe
    Abstract:

    Background Adiposity is associated with larger left ventricular mass in children and adults. The role of Body Fat Distribution in these associations is not clear. We examined the associations of Body Fat Distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. Methods and Results In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on Body mass index, lean mass index, Fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All Body Fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14-0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on Body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher Fat mass measures were inversely associated with these cardiac measures (all P<0.05). Conclusions Higher childhood Body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than Fat mass. Fat mass may influence cardiac structures at older ages.

  • Body Fat Distribution overweight and cardiac structures in school age children a population based cardiac magnetic resonance imaging study
    Stroke, 2020
    Co-Authors: Liza Toemen, S M S Santos, A A Roest, G Jelic, A Van Delugt, J F Felix, W A Helbing, R Gaillard, V W V Jaddoe
    Abstract:

    BACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of Body Fat Distribution in these associations is not clear. We examined the associations of Body Fat Distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. METHODS AND RESULTS: In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on Body mass index, lean mass index, Fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All Body Fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94–1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14–0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on Body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher Fat mass measures were inversely associated with these cardiac measures (all P<0.05). CONCLUSIONS: Higher c

Sara L Pulit - One of the best experts on this subject based on the ideXlab platform.

  • microrna 196a links human Body Fat Distribution to adipose tissue extracellular matrix composition
    EBioMedicine, 2019
    Co-Authors: Catriona Hilton, Sara L Pulit, Matt J Neville, Katherine E Pinnick, Laura B L Wittemans, Marijana Todorcevic, Jianan Luan
    Abstract:

    Abstract Background Abdominal Fat mass is associated with metabolic risk whilst gluteal femoral Fat is paradoxically protective. MicroRNAs are known to be necessary for adipose tissue formation and function but their role in regulating human Fat Distribution remains largely unexplored. Methods An initial microarray screen of abdominal subcutaneous and gluteal adipose tissue, with validatory qPCR, identified microRNA-196a as being strongly differentially expressed between gluteal and abdominal subcutaneous adipose tissue. Findings We found that rs11614913, a SNP within pre-miR-196a-2 at the HOXC locus, is an eQTL for miR-196a expression in abdominal subcutaneous adipose tissue (ASAT). Observations in large cohorts showed that rs11614913 increased waist-to-hip ratio, which was driven specifically by an expansion in ASAT. In further experiments, rs11614913 was associated with adipocyte size. Functional studies and transcriptomic profiling of miR-196a knock-down pre-adipocytes revealed a role for miR-196a in regulating pre-adipocyte proliferation and extracellular matrix pathways. Interpretation These data identify a role for miR-196a in regulating human Body Fat Distribution. Fund This work was supported by the Medical Research Council and Novo Nordisk UK Research Foundation ( G1001959 ) and Swedish Research Council . We acknowledge the OBB-NIHR Oxford Biomedical Research Centre and the British Heart Foundation (BHF) ( RG/17/1/32663 ). Work performed at the MRC Epidemiology Unit was funded by the United Kingdom's Medical Research Council through grants MC_UU_12015/1 , MC_PC_13046 , MC_PC_1304 8 and MR/L00002/1 .

  • meta analysis of genome wide association studies for Body Fat Distribution in 694 649 individuals of european ancestry
    Human Molecular Genetics, 2019
    Co-Authors: Sara L Pulit, Charli Stoneman, Andrew P Morris, Andrew R Wood, Craig A Glastonbury, Jessica Tyrrell, Loic Yengo
    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.

  • meta analysis of genome wide association studies for Body Fat Distribution in 694 649 individuals of european ancestry
    bioRxiv, 2018
    Co-Authors: Sara L Pulit, Teresa Ferreira, Charli Stoneman, Andrew P Morris, Andrew R Wood, Craig A Glastonbury, Jessica Tyrrell, Loic Yengo, Eirini Marouli, Jian Yang
    Abstract:

    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 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 publically available, will inform the biology of Body Fat Distribution and its relationship with disease.

  • sexual dimorphisms in genetic loci linked to Body Fat Distribution
    Bioscience Reports, 2017
    Co-Authors: Sara L Pulit, T Karaderi, Cecilia M Lindgren
    Abstract:

    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.

Liza Toemen - One of the best experts on this subject based on the ideXlab platform.

  • Body Fat Distribution overweight and cardiac structures in school age children a population based cardiac magnetic resonance imaging study
    Journal of the American Heart Association, 2020
    Co-Authors: Liza Toemen, A A Roest, G Jelic, J F Felix, W A Helbing, R Gaillard, Susana Santos, Aad Van Der Lugt, V W V Jaddoe
    Abstract:

    Background Adiposity is associated with larger left ventricular mass in children and adults. The role of Body Fat Distribution in these associations is not clear. We examined the associations of Body Fat Distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. Methods and Results In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on Body mass index, lean mass index, Fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All Body Fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94-1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14-0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on Body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher Fat mass measures were inversely associated with these cardiac measures (all P<0.05). Conclusions Higher childhood Body mass index is associated with a larger right and left ventricular size. This association is influenced by higher lean mass. In childhood, lean mass may be a stronger determinant of heart growth than Fat mass. Fat mass may influence cardiac structures at older ages.

  • Body Fat Distribution overweight and cardiac structures in school age children a population based cardiac magnetic resonance imaging study
    Stroke, 2020
    Co-Authors: Liza Toemen, S M S Santos, A A Roest, G Jelic, A Van Delugt, J F Felix, W A Helbing, R Gaillard, V W V Jaddoe
    Abstract:

    BACKGROUND: Adiposity is associated with larger left ventricular mass in children and adults. The role of Body Fat Distribution in these associations is not clear. We examined the associations of Body Fat Distribution and overweight with cardiac measures obtained by cardiac magnetic resonance imaging in school-age children. METHODS AND RESULTS: In a population-based cohort study including 2836 children, 10 years of age, we used anthropometric measures, dual-energy X-ray absorptiometry, and magnetic resonance imaging to collect information on Body mass index, lean mass index, Fat mass index, and abdominal visceral adipose tissue index. Indexes were standardized by height. Cardiac measures included right and left ventricular end-diastolic volume, left ventricular mass, and mass-to-volume ratio as a marker for concentricity. All Body Fat measures were positively associated with right and left ventricular end-diastolic volumes and left ventricular mass, with the strongest associations for lean mass index (all P<0.05). Obese children had a 1.12 standard deviation score (95% CI, 0.94–1.30) larger left ventricular mass and a 0.35 standard deviation score (95% CI, 0.14–0.57) higher left ventricular mass-to-volume ratio than normal weight children. Conditional on Body mass index, higher lean mass index was associated with higher right and left ventricular end-diastolic volume and left ventricular mass, whereas higher Fat mass measures were inversely associated with these cardiac measures (all P<0.05). CONCLUSIONS: Higher c

A R Genazzani - One of the best experts on this subject based on the ideXlab platform.

  • prospective evaluation of Body weight and Body Fat Distribution in early postmenopausal women with and without hormonal replacement therapy
    Maturitas, 2001
    Co-Authors: M Gambacciani, M Ciaponi, Barbara Cappagli, L De Simone, R Orlandi, A R Genazzani
    Abstract:

    Aims: In order to assess the effects of menopause and hormonal replacement therapy (HRT) on Body weight and Body Fat Distribution (determined by dual energy X-ray), early postmenopausal women were given either oral calcium (500 mg/day, control group, n=13) or HRT, a combination of estradiol valerate (EV, 2 mg/day for 21 days) with cyproterone acetate (CPA, 1 mg/day in the last 10 days of the treatment cycle, n=18; Climen®, Schering). Results: There were no differences in basal Body weight and Body Fat Distribution in the two groups before the study. In control group, a significant (P<0.05) increase in Body weight (from 63.5±2.0 to 68.7±2.0 kg after 36 months) paralleled a shift to a prevalent central, android Fat Distribution with a slight but significant (P<0.05) increase in total Body Fat mass (from 23.4±2.1 to 29.1±2.1 kg), an increase in trunk (from 10.1±0.4 to 12.7±0.4 kg, P<0.05), arms (from 2.4±0.2 to 2.9±0.2 kg, P<0.05) and legs (from 6.5±0.4 to 7.8±0.4 kg, P<0.05) Fat. In the HRT group total Body bone mineral showed a significant increase (from 1086±21 to 1128±19 mg/cm2, P<0.05) increase after 36 months, with no significant increase in Body weight (from 62.6±1.8 to 65.0±1.9 kg), and no modifications in trunk (from 10.0±0.2 to 10.1±0.2 kg) and arms (from 2.4±0.1 to 2.6±0.1 kg) Fat, but a significant increase in legs Fat (from 6.9±0.3 to 9.9±0.4 kg, P<0.05). Conclusion: Present results demonstrate that menopause is associated with an accelerated increase in Body weight and Body Fat, with a prevalent central, android Fat Distribution, that can be counteracted at least in part by oral HRT.

  • Body weight Body Fat Distribution and hormonal replacement therapy in early postmenopausal women
    The Journal of Clinical Endocrinology and Metabolism, 1997
    Co-Authors: M Gambacciani, M Ciaponi, Barbara Cappagli, L Piaggesi, L De Simone, R Orlandi, A R Genazzani
    Abstract:

    Body weight was measured, and Body Fat Distribution was determined by dual energy x-ray in early postmenopausal women given either oral calcium (500 mg/day; control group; n = 12) or hormonal replacement therapy (HRT), a combination of estradiol valerate (2 mg/day for 21 days) with cyproterone acetate (1 mg/day in the last 10 days of the treatment cycle; n = 15). There were no differences in basal Body weight or Body Fat Distribution in the two groups before the study. In the control group, a significant (P < 0.05) increase in Body weight (from 63.6 +/- 2.2 to 65.2 +/- 1.9 kg [corrected] after 12 months) paralleled a slight, but significant (P < 0.05), increase in total Body Fat mass (from 23.8 +/- 2.2 to 24.7 +/- 2.2 kg), with an increase in Fat in the trunk (from 10.2 +/- 0.4 to 11.3 +/- 0.4 kg; P < 0.01) and arms (from 2.4 +/- 0.5 to 2.7 +/- 0.2 kg; P < 0.05). These findings demonstrate a shift to a prevalent central android Fat Distribution after 12 months of observation in untreated postmenopausal women. Conversely, in the HRT group, total Body bone mineral showed a significant (from 1089 +/- 28 to 1106 +/- 29 mg/cm2; P < 0.05) increase after 12 months, with no significant increase in Body weight (from 62.2 +/- 1.6 to 62.7 +/- 1.6 kg), and no modifications in trunk (from 10.0 +/- 0.2 to 9.8 +/- 0.3 kg) and arm (from 2.43 +/- 0.2 to 2.5 +/- 0.1 kg) Fat, but a significant increase in leg Fat (from 7.1 +/- 0.3 to 8.3 +/- 0.4 kg; P < 0.05). The present results suggest that HRT can counteract at least in part the postmenopausal increase in Body weight and Body Fat and prevent central Body Fat Distribution after menopause.