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Pancreatic‐derived factor promotes lipogenesis in the mouse liver: Role of the Forkhead box 1 signaling pathway
Author(s) -
Li Jing,
Chi Yujing,
Wang Chunjiong,
Wu Jing,
Yang Hang,
Zhang Dongjuan,
Zhu Yi,
Wang Nanping,
Yang Jichun,
Guan Youfei
Publication year - 2011
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24295
Subject(s) - foxo1 , lipogenesis , endocrinology , medicine , gene knockdown , insulin resistance , gene silencing , insulin , steatosis , biology , small interfering rna , insulin receptor , chemistry , protein kinase b , cancer research , signal transduction , microbiology and biotechnology , apoptosis , lipid metabolism , cell culture , transfection , biochemistry , gene , genetics
Pancreatic‐derived factor (PANDER) is a pancreatic islet‐specific cytokine that cosecretes with insulin and is important for β cell function. Here, we show that PANDER is constitutively expressed in hepatocytes, and its expression is significantly increased in steatotic livers of diabetic insulin‐resistant db/db mice and mice fed a high‐fat diet. Overexpression of PANDER in the livers of C57Bl/6 mice promoted lipogenesis, with increased Forkhead box 1 (FOXO1) expression, whereas small interfering RNA–mediated knockdown of hepatic PANDER significantly attenuated steatosis, with reduced FOXO1 expression in db/db mice. Hepatic PANDER silencing also attenuated insulin resistance and hyperglycemia in db/db mice. In cultured hepatocytes, PANDER overexpression induced lipid deposition, increased FOXO1 expression, and suppressed insulin‐stimulated Akt activation and FOXO1 inactivation. Moreover, FOXO1 overexpression increased PANDER expression in cultured hepatocytes and mouse livers. Conclusion: PANDER promotes lipogenesis and compromises insulin signaling in the liver by increasing FOXO1 activity. PANDER may represent a potential therapeutic target for the treatment of fatty liver and insulin resistance. (H EPATOLOGY 2011;)