| First Author | Zhuang LN | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 32 | Pages | 28403-13 |
| PubMed ID | 21700709 | Mgi Jnum | J:175917 |
| Mgi Id | MGI:5287930 | Doi | 10.1074/jbc.M111.256099 |
| Citation | Zhuang LN, et al. (2011) 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 |
| abstractText | One of the master regulators of adipogenesis and macrophage function is peroxisome proliferator-activated receptor-gamma (PPARgamma). Here, we report that a deficiency of beta-arrestin-1 expression affects PPARgamma-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that beta-arrestin-1 interacts with PPARgamma. beta-Arrestin-1 suppressed the formation of a complex between PPARgamma and 9-cis-retinoic acid receptor-alpha through its direct interaction with PPARgamma. The interaction of beta-arrestin-1 with PPARgamma repressed PPARgamma/9-cis-retinoic acid receptor-alpha function but promoted PPARgamma/nuclear receptor corepressor function in PPARgamma-mediated adipogenesis and inflammatory gene expression. Consistent with these results, a deficiency of beta-arrestin-1 binding to PPARgamma abolished its suppression of PPARgamma-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARgamma by beta-arrestin-1 is critical. Furthermore, in vivo expression of beta-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 beta-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders. |
