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


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.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.|Division of Hepatobiliary and Pancreatic Diseases, Osaka-Rosai Hospital, Sakai, Japan.
Atsushi
A
Hosui
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Tomohide
T
Tatsumi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Hayato
http://orcid.org/0000-0003-2488-7315
H
Hikita
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Yoshinobu
Y
Saito
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.|Division of Hepatobiliary and Pancreatic Diseases, Osaka-Rosai Hospital, Sakai, Japan.
Naoki
N
Hiramatsu
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.|Division of Hepatobiliary and Pancreatic Diseases, Osaka-Rosai Hospital, Sakai, Japan.
Masahiko
M
Tsujii
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Lothar
L
Hennighausen
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Japan.
Tetsuo
T
Takehara
CD36; PPARγ; STAT5; fatty liver; triglyceride