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PTEN influences insulin and lipid metabolism in bovine hepatocytes in vitro

Published online by Cambridge University Press:  01 March 2019

Qinghua Deng
Affiliation:
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
Dehui Ma
Affiliation:
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
Guoquan Sun
Affiliation:
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
Xue Yuan
Affiliation:
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China
Zhe Wang
Affiliation:
College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China
Guowen Liu*
Affiliation:
College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, China College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, Jilin, 130062, China
*
Author for correspondence: Guowen Liu, Email: liuguowen2008@163.com

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.

Type
Research Article
Copyright
Copyright © Hannah Dairy Research Foundation 2019 

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