PTEN influences insulin and lipid metabolism in bovine hepatocytes in vitro. Issue 1 (1st March 2019)

• Record Type: Journal Article
• Authors: Deng, Qinghua; Ma, Dehui; Sun, Guoquan; Yuan, Xue; Wang, Zhe; Liu, Guowen
• Is Part Of: Journal of dairy research. Volume 86:Issue 1(2019)
• Page Start: 73
• Page End: 76
• Publication Date: 2019-03-01
• Subjects: Hepatocyte, -- insulin resistance, -- PI3K/AKT, -- PTEN; Dairying -- Periodicals; Dairying -- Research -- Periodicals; 636.214205
• DOI: 10.1017/S0022029919000128
• Languages: English
• ISSNs: 0022-0299

Abstract

Abstract: Dairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor and also a negative regulator of insulin signaling and peripheral insulin sensitivity. We investigated the hypothesis that PTEN may affect the insulin pathway-mediated hepatic glucose and lipid metabolism in dairy cows. Adenovirus vectors that over-express and silence PTEN were constructed, and then transfected into hepatocytes isolated from calves to investigate the effect of PTEN on PI3K/AKT signaling pathway. PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3β (GSK-3β) and expression of sterol regulatory element-binding protein-1c (SREBP-1c). Increased GSK-3β phosphorylation further up-regulated expression of the key enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase) involved in gluconeogenesis. Furthermore, the expression of SREBP-1c target gene fatty acid synthase (FAS) also increased significantly. We further showed that PTEN over-expression could reverse the above results. PTEN negatively regulates the enzymes involved in hepatic gluconeogenesis and lipid synthesis, which suggests that PTEN may be a therapeutic target for ketosis and fatty liver in dairy cows.