期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 305, 期 4, 页码 E530-E539出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00640.2012
关键词
peroxisome proliferatior-activated receptor-gamma 2; obesity; adipogenesis; adipogenic differentiation; autophagy; proteasome-dependent protein degradation
资金
- American Diabetes Association Basic Science Award [7-06-RA-165]
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-gamma (PPAR gamma). We show that adipogenic differentiation of 3T3-L1 preadipocytes is associated with activation of autophagy and increased PPAR gamma 2 protein level. Treatment with CQ, shRNA-mediated knockdown, or genetic engineering-induced deletion of autophagy-related gene 5 (Atg5) promoted proteasome-dependent PPAR gamma 2 degradation and attenuated adipogenic differentiation. Therefore, activated autophagy increases PPAR gamma 2 stability and promotes adipogenic differentiation, and inhibition of autophagy may prevent high-fat diet-induced obesity and the consequential type 2 diabetes.
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