Beta-arrestin-1 protein represses adipogenesis and inflammatory responses through its interaction with peroxisome proliferator-activated receptor-gamma (PPARgamma).
J Biol Chem
; 286(32): 28403-13, 2011 Aug 12.
Article
en En
| MEDLINE
| ID: mdl-21700709
ABSTRACT
One of the master regulators of adipogenesis and macrophage function is peroxisome proliferator-activated receptor-γ (PPARγ). Here, we report that a deficiency of ß-arrestin-1 expression affects PPARγ-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that ß-arrestin-1 interacts with PPARγ. ß-Arrestin-1 suppressed the formation of a complex between PPARγ and 9-cis-retinoic acid receptor-α through its direct interaction with PPARγ. The interaction of ß-arrestin-1 with PPARγ repressed PPARγ/9-cis-retinoic acid receptor-α function but promoted PPARγ/nuclear receptor corepressor function in PPARγ-mediated adipogenesis and inflammatory gene expression. Consistent with these results, a deficiency of ß-arrestin-1 binding to PPARγ abolished its suppression of PPARγ-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARγ by ß-arrestin-1 is critical. Furthermore, in vivo expression of ß-arrestin-1 (but not the binding-deficient mutant) significantly repressed adipogenesis, macrophage infiltration, and diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Therefore, our findings not only reveal a molecular mechanism for the modulation of obesity by ß-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Arrestinas
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PPAR gamma
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Adipogénesis
Límite:
Animals
Idioma:
En
Año:
2011
Tipo del documento:
Article