학술논문
Genetics of sexually dimorphic adipose distribution in humans
Document Type
Article
Author
Hansen, Grace T.; Sobreira, Débora R.; Weber, Zachary T.; Thornburg, Alexis G.; Aneas, Ivy; Zhang, Li; Sakabe, Noboru J.; Joslin, Amelia C.; Haddad, Gabriela A.; Strobel, Sophie M.; Laber, Samantha; Sultana, Farhath; Sahebdel, Faezeh; Khan, Kohinoor; Li, Yang I.; Claussnitzer, Melina; Ye, Liang; Battaglino, Ricardo A.; Nóbrega, Marcelo A.
Source
Nature Genetics; March 2023, Vol. 55 Issue: 3 p461-470, 10p
Subject
Language
ISSN
10614036; 15461718
Abstract
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 Aluretrotransposons 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.