Genetics of sexually dimorphic adipose distribution in humans.
Nat Genet
; 55(3): 461-470, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36797366
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Retroelementos
/
Obesidade
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article