title: Deletion of steroid receptor coactivator-3 gene ameliorates hepatic steatosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings indicate a crucial role for SRC-3 in regulating hepatic lipid metabolism and provide the possible novel inner mechanisms.
authors.affiliation: 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.
authors.forename: Xinran
authors.initials: X
authors.lastname: Ma
authors.forename: Lingyan
authors.initials: L
authors.lastname: Xu
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease; D056921:Nuclear Receptor Coactivator 3 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D051837:COUP Transcription Factor II; D004041:Dietary Fats; D047493:PPAR alpha; C000607071:RARA protein, human; D034741:RNA, Small Interfering; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; C538866:NCOA3 protein, human; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3