| Objective:Obesity is closely associated with non-alcoholic fatty liver disease(NAFLD),and elevated serum palmitate is the link between obesity and excessive hepatic lipid accumulation.Forkhead box O-1(FoxO1)is one of the FoxO family members of transcription factors and can stimulate adipose triglyceride lipase(ATGL)and suppress its inhibitor G0/G1 switch gene 2(G0S2)expression in the liver.However,previous researches have also shown conflicting results regarding the role of FoxO1 in hepatic lipid accumulation.We therefore examined the role of FoxO1 as a downstream suppressor to palmitate-stimulated hepatic steatosis.Methods:HepG2 hepatocytes were exposed to palmitate,palmitate in integration with pReceiver-M98-FoxO1 or G0S2 siRNA.The intracellular lipid accumulation was tested by Oil Red O stain.The lipolytic activity was demonstrated by the glycerol amount released into the media.The expression of concerning genes was determined through quantitative real-time PCR and Western blotting analysis.Results:Palmitate significantly promoted lipid accumulation and inhibited lipolysis in human HepG2 hepatoma cells.Palmitate also significantly reduced FoxO1,ATGL and its activator comparative gene identification-58(CGI-58)expression and increased peroxisome proliferator-activated receptor ?(PPAR?)and its target gene G0S2 expression.FoxO1 overexpression significantly increased palmitate-inhibited ATGL andCGI-58 expression and reduced palmitate-induced PPAR? and G0S2 expression.FoxO1 overexpression also inhibited lipid accumulation and promoted lipolysis in palmitate-treated hepatocytes.Moreover,G0S2 knockdown significantly inhibited lipid accumulation and promoted lipolysis in palmitate-treated hepatocytes,whereas G0S2 knockdown did not affect FoxO1,PPAR?,ATGL and CGI-58 expression.Conclusion:Palmitate suppresses FoxO1 expression in the liver,and FoxO1 can alleviate palmitate-induced hepatic fat accumulation through stimulating ATGL-dependent lipolysis. |
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