| First Author | Hansen GT | Year | 2023 |
| Journal | Nat Genet | Volume | 55 |
| Issue | 3 | Pages | 461-470 |
| PubMed ID | 36797366 | Mgi Jnum | J:339877 |
| Mgi Id | MGI:7524481 | Doi | 10.1038/s41588-023-01306-0 |
| Citation | Hansen GT, et al. (2023) Genetics of sexually dimorphic adipose distribution in humans. Nat Genet 55(3):461-470 |
| abstractText | 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. |
