%0 Journal Article
%T Saturated Fatty Acid-Induced Cytotoxicity in Liver Cells Does Not Involve Phosphatase and Tensin Homologue Deleted on Chromosome 10
%A Dong Wang
%A Yuren Wei
%A Melinda Frye
%A Christopher L. Gentile
%A Michael J. Pagliassotti
%J Journal of Nutrition and Metabolism
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/514206
%X Liver specific deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) induces steatosis and hypersensitivity to insulin. Saturated fatty acids, which induce endoplasmic reticulum stress and cell death, appear to increase PTEN, whereas unsaturated fatty acids which do not induce endoplasmic reticulum stress or cell death reduce this protein. In the present study, the role of PTEN in saturated fatty acid-induced cytotoxicity was examined in H4IIE and HepG2 liver cells. Palmitate and stearate increased the expression of PTEN, whereas the unsaturated fatty acids, oleate and linoleate, reduced PTEN expression in both cell types. SiRNA-mediated knockdown of PTEN did not increase liver cell triglyceride stores or reduce palmitate- or stearate-mediated ER stress or apoptosis. These results suggest that PTEN does not play a significant role in saturated fatty acid-induced cytotoxicity in these liver cell models and in the absence of insulin. 1. Introduction Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder characterized by an increase in the hepatic triglyceride pool (steatosis) and, in some individuals, development of nonalcoholic steatohepatitis (NASH) [1]. Accumulating data suggest that, in addition to their role in the development of hepatic steatosis [2], fatty acids play an important role in disease progression. Free fatty acids are elevated in patients with NASH and are positively correlated with disease severity [3, 4]. Suppression of circulating fatty acids improved hepatic insulin sensitivity and reduced liver enzymes in healthy individuals [5]. Data such as these have led to the emerging concept that elevated fatty acids and products of fatty acid metabolism, rather than the triglyceride pool per se, promote hepatotoxicity and disease progression in NAFLD. Indeed, hepatic triglycerides are higher in patients with benign steatosis compared to those with NASH [6], and stimulation of lipogenesis and/or fatty acid oxidation protects against palmitate-induced cell death in ¦Â-cells [7]. The cytotoxic response to elevated fatty acids appears to be specific to or made more severe by long-chain saturated fatty acids [8¨C11]. In hepatocytes, saturated fatty acids promote endoplasmic reticulum (ER) stress and apoptosis [11, 12], both of which are characteristic features of NAFLD [13, 14]. The toxic effects of saturated fatty acids may be due to their inability, relative to unsaturated fatty acids, to be esterified and incorporated into triglyceride [7, 15¨C17]. Lipid phosphatase and tensin homolog
%U http://www.hindawi.com/journals/jnme/2013/514206/