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United States Department of Agriculture

Agricultural Research Service

Title: Nonalcoholic steatohepatitis is associated with increased hepatocyte apoptosis, JNK activation and Bax protein

Authors
item Wang, Yan - JM USDA HNRCA @ TUFTS
item Ausman, Lynne - JM USDA HNRCA @ TUFTS
item Russell, Robert
item Greenberg, Andrew
item Wang, Xiang-Dong

Submitted to: Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 2007
Publication Date: April 5, 2008
Citation: Wang, Y., Ausman, L., Russell, R., Greenberg, A.S., Wang, X. 2008. Nonalcoholic steatohepatitis is associated with increased hepatocyte apoptosis, JNK activation and Bax protein. FASEB Journal. 22:297.6.

Technical Abstract: High-fat diet enriched in omega-6 polyunsaturated fatty acids (PUFA) induces non-alcoholic steatohepatitis (NASH). The potential mechanisms involved in this process have not been defined. Male Sprague-Dawley rats were fed ad libitum Lieber-DeCarli diet at either 35% energy from fat (control) or 71% energy from fat (high-fat) enriched in omega-6 PUFA for 6 weeks. Histopathological examination showed key features of NASH (steatosis, inflammatory cell infiltration, ballooning degeneration) by the high-fat diet, which were accompanied with induction of tumor necrosis factor-a mRNA, high lipid peroxidation products (4-hydroxynonenal and malondialdehyde), and cytochrome p4502E1. The high-fat diet caused significantly increased apoptotic cells (3.3 +/- 0.4 [Mean +/- SD] vs.1.8 +/- 0.1/field as assessed by the Terminal dUTP Nick-End Labeling assay) and also activated caspase-3 and poly ADP-ribose polymerase in liver. This increased apoptosis was related with higher levels of phosphorylated c-Jun-NH2-kinase (JNK) and pro-apoptotic Bax protein but not anti-apoptotic proteins Bcl-2 and Bcl-xl. This study indicates that the high oxidative stress, increased JNK activation, and imbalance of pro- and anti-apoptotic proteins in Bcl-2 family all contribute to the high fat diet-induced apoptosis that may play a significant role in the pathogenesis of NASH.

Last Modified: 8/22/2014
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