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High‐fat diet with adequate methionine and choline levels induces hepatic insulin resistance via Akt signaling pathway in a rodent model for Non‐alcoholic Steatohepatitis.
Author(s) -
Sundaresan Sinju,
Vijayagopal Parakat,
Mills Nathaniel,
Imrhan Victorine,
Prasad Chandan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.934.2
Subject(s) - insulin resistance , steatohepatitis , protein kinase b , medicine , endocrinology , steatosis , insulin receptor , fatty liver , irs1 , insulin , triglyceride , phosphorylation , insulin receptor substrate , chemistry , biology , biochemistry , cholesterol , disease
Signaling pathways involved in hepatic insulin resistance that develops in animal models of non‐alcoholic steatohepatitis (NASH) have not been adequately investigated. In this study hepatic insulin resistance was investigated in livers of C57BL/6J mice by determining protein and gene expressions of insulin receptor (IR), insulin receptor substrate (IRS), Akt and their phosphorylated forms (p‐IR, p‐IRS, and p‐Akt). Forty C57BL/6J mice, divided into control and high‐fat groups were fed low‐fat diet or HFD ad libitum for 20 weeks. At the end of 20 weeks animals were sacrificed and assays were performed for blood biomarkers typical of human NASH. As reported earlier, HFD led to increased triglyceride accumulation in the liver and induced histopathological features of human NASH including hepatic steatosis, ballooning, inflammation and fibrosis. At the end of 20 weeks, ratio of p‐IR/IR, p‐IRS/IRS, and p‐Akt/Akt expressions were significantly lower in the HF group than controls along with decreased expression's of total and phosphorylated forms. Significant reductions in the gene expressions of IR, IRS‐2, Akt and their phosphorylated forms were observed in the HF group compared to controls. Thus, hepatic insulin resistance in this NASH model is mediated via Akt signaling pathway. Supported by Research Enhancement Program, TWU and Texas Department of Agriculture