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Am J Physiol Endocrinol Metab. 2013 Aug 15;305(4):E530-9. doi: 10.1152/ajpendo.00640.2012. Epub 2013 Jun 25.

Autophagy is involved in adipogenic differentiation by repressesing proteasome-dependent PPARγ2 degradation.

Author information

1
Departments of Medicine, Pharmacology, and Molecular Physiology and Biological Physics and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia;

Abstract

Animal studies have shown that autophagy is essential in the process of obesity. Here, we performed daily injection of the autophagy inhibitor chloroquine (CQ) in mice and found that systemic administration of CQ blocks high-fat diet-induced obesity. To investigate the potential underlying molecular mechanism, we employed genetic and pharmacological interventions in cultured preadipocytes to investigate the role of autophagy in the control of the expression of the adipogenic regulator peroxisome proliferatior-activated receptor-γ (PPARγ). We show that adipogenic differentiation of 3T3-L1 preadipocytes is associated with activation of autophagy and increased PPARγ2 protein level. Treatment with CQ, shRNA-mediated knockdown, or genetic engineering-induced deletion of autophagy-related gene 5 (Atg5) promoted proteasome-dependent PPARγ2 degradation and attenuated adipogenic differentiation. Therefore, activated autophagy increases PPARγ2 stability and promotes adipogenic differentiation, and inhibition of autophagy may prevent high-fat diet-induced obesity and the consequential type 2 diabetes.

KEYWORDS:

adipogenesis; adipogenic differentiation; autophagy; obesity; peroxisome proliferatior-activated receptor-γ2; proteasome-dependent protein degradation

PMID:
23800883
PMCID:
PMC5504416
DOI:
10.1152/ajpendo.00640.2012
[Indexed for MEDLINE]
Free PMC Article

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