Genetics of sexually dimorphic adipose distribution in humans.
Grace T HansenDébora R SobreiraZachary T WeberAlexis G ThornburgIvy AneasLi ZhangNoboru J SakabeAmelia C JoslinGabriela A HaddadSophie M StrobelSamantha LaberFarhath SultanaFaezeh SahebdelKohinoor KhanYang I LiMelina ClaussnitzerLiang YeRicardo A BattaglinoMarcelo Aguiar NobregaPublished in: Nature genetics (2023)
Obesity-associated morbidity is exacerbated by abdominal obesity, which can be measured as the waist-to-hip ratio adjusted for the body mass index (WHRadjBMI). Here we identify genes associated with obesity and WHRadjBMI and characterize allele-sensitive enhancers that are predicted to regulate WHRadjBMI genes in women. We found that several waist-to-hip ratio-associated variants map within primate-specific Alu retrotransposons harboring a DNA motif associated with adipocyte differentiation. This suggests that a genetic component of adipose distribution in humans may involve co-option of retrotransposons as adipose enhancers. We evaluated the role of the strongest female WHRadjBMI-associated gene, SNX10, in adipose biology. We determined that it is required for human adipocyte differentiation and function and participates in diet-induced adipose expansion in female mice, but not males. Our data identify genes and regulatory mechanisms that underlie female-specific adipose distribution and mediate metabolic dysfunction in women.
Keyphrases
- insulin resistance
- polycystic ovary syndrome
- high fat diet induced
- adipose tissue
- body mass index
- metabolic syndrome
- skeletal muscle
- type diabetes
- genome wide
- weight gain
- copy number
- endothelial cells
- physical activity
- oxidative stress
- gene expression
- big data
- pregnant women
- total hip arthroplasty
- bioinformatics analysis
- high density
- deep learning