Signal transducer and activator of transcription 5 plays a crucial role in hepatic lipid metabolism through regulation of CD36 expression.

Aim Liver-specific signal transducer and activator of transcription (STAT)5-deficient mice (STAT5KO) show lipid accumulation in the liver. We investigated the role of hepatic STAT5 in lipid metabolism in vitro and in vivo. Methods and Results High expression of CD36, one of the receptors for free fatty acids, is associated with a high concentration of hepatic triglyceride (TG) in STAT5KO mice. Peroxisome proliferator-activated receptor (PPAR)γ, one of the regulatory factors of CD36, was upregulated and microRNA (miR)-20b was downregulated in STAT5KO mice. Reporter assays revealed direct regulation involving miR-20b and the 3′-untranslated region of CD36 mRNA. Treatment with free fatty acids enhanced accumulation of TG in STAT5-deleted hepatoma cells, and this was partially canceled by introduction of siRNA for PPARγ and/or pre-miR-20b through inhibition of CD36 expression. In vivo, STAT5/CD36 double knockout mice displayed hepatic TG was decreased compared to STAT5KO mice and it was also reduced by treatment with PPARγ antagonists, GW9662, and/or pre-miR-20b. Conclusions Signal transducer and activator of transcription 5 plays an important role in hepatic fat metabolism through regulation of CD36, and is a potential therapeutic candidate for liver steatosis. [ABSTRACT FROM AUTHOR]