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J Hepatol. 2011 Aug;55(2):445-52. doi: 10.1016/j.jhep.2010.11.022. Epub 2010 Dec 22.

Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis.

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Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chongqing Road, Shanghai 200025, China.



Excess dietary fat can cause hepatic steatosis, which can progress into severe liver disorders including steatohepatitis and cirrhosis. Steroid receptor coactivator-3 (SRC-3), a member of the p160 coactivator family, is reported as a key regulator of adipogenesis and energy homeostasis. We sought to determine the influence of SRC-3 on hepatic steatosis and the mechanism beneath.


The influence of siRNA-mediated SRC-3 silencing on hepatic lipid accumulation was assessed in HepG2 cells. The molecular mechanism of SRC-3 regulation of hepatic lipid metabolism was also studied. Moreover, the effect of SRC-3 ablation on hepatic steatosis was examined in SRC-3 deficient mice.


In this study, we report that SRC-3 ablation reduces palmitic acid-induced lipid accumulation in HepG2 cells. Moreover, deletion of SRC-3 ameliorates hepatic steatosis and inflammation response in mice fed a high fat diet (HFD). These metabolic improvements can presumably be explained by the reduction in chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) expression and the subsequent elevation in peroxisome proliferator-activated receptor α (PPARα) level. At the molecular level, SRC-3 interacts with retinoic receptor α (RARα) to activate COUP-TFII expression under all-trans retinoic acid (ARTA) treatment.


These findings indicate a crucial role for SRC-3 in regulating hepatic lipid metabolism and provide the possible novel inner mechanisms.

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