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 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.
Original language | English (US) |
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Pages (from-to) | 461-470 |
Number of pages | 10 |
Journal | Nature Genetics |
Volume | 55 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't