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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 β-arrestin-1 expression affects PPARγ-mediated expression of lipid metabolic genes and
inflammatory genes. Further mechanistic studies revealed that β-arrestin-1 interacts with PPARγ. β-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 β-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 β-arrestin-1 binding to PPARγ abolished its
suppression of PPARγ-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARγ
by β-arrestin-1 is critical. Furthermore, in vivo expression of β-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 β-arrestin-1 but also suggest a potential tactical approach
against obesity and its associated metabolic disorders.
Journal of Biological Chemistry 08/2011; 286(32):28403-28413. · 4.77 Impact Factor
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[show abstract]
[hide abstract]
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 β-arrestin-1 expression affects PPARγ-mediated expression of lipid metabolic genes and inflammatory genes. Further mechanistic studies revealed that β-arrestin-1 interacts with PPARγ. β-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 β-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 β-arrestin-1 binding to PPARγ abolished its suppression of PPARγ-dependent adipogenesis and inflammatory responses. These results indicate that the regulation of PPARγ by β-arrestin-1 is critical. Furthermore, in vivo expression of β-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 β-arrestin-1 but also suggest a potential tactical approach against obesity and its associated metabolic disorders.
Journal of Biological Chemistry 06/2011; 286(32):28403-13. · 4.77 Impact Factor
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ABSTRACT: Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis, and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here, we report that β-arrestin-1 knock-out mice are susceptible to diet-induced obesity. Knock-out of the gene encoding β-arrestin-1 caused increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed a high-fat diet. In β-arrestin-1 knock-out mice, we observed disrupted food intake and energy expenditure and increased macrophage infiltration in white adipose tissue. At the molecular level, β-arrestin-1 deficiency affected the expression of many lipid metabolic genes and inflammatory genes in adipose tissue. Consistently, transgenic overexpression of β-arrestin-1 repressed diet-induced obesity and improved glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that β-arrestin-1 plays a role in metabolism regulation.
Journal of Biological Chemistry 05/2011; 286(32):28396-402. · 4.77 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Diet-related obesity is a major metabolic disorder. Excessive fat mass is associated with type 2 diabetes, hepatic steatosis
and arteriosclerosis. Dysregulation of lipid metabolism and adipose tissue function contributes to diet-induced obesity. Here,
we report that βarrestin1 knockout mice are susceptible to diet-induced obesity. Knockout of the gene encoding βarrestin1
causes increased fat mass accumulation and decreased whole-body insulin sensitivity in mice fed with a high fat diet. In βarrestin1
knockout mice, we find disrupted food intake and energy expenditure, and increased macrophages infiltration in white adipose
tissue. At the molecular level, βarrestin1 deficiency affects the expression of many lipid metabolic genes and inflammatory
genes in adipose tissue. Consistently, transgenic over expression of βarrestin1 represses diet-induced obesity and improves
glucose tolerance and systemic insulin sensitivity. Thus, our findings reveal that βarrestin1 plays a role in the metabolism
regulation.
Journal of Biological Chemistry 05/2011; · 4.77 Impact Factor
