Fatty Acid Desaturase Involvement in Non-Alcoholic Fatty Liver Disease Rat Models: Oxidative Stress Versus Metalloproteinases

脂肪酸去饱和酶参与非酒精性脂肪肝大鼠模型:氧化应激与金属蛋白酶

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作者:Giuseppina Palladini, Laura G Di Pasqua, Clarissa Berardo, Veronica Siciliano, Plinio Richelmi, Barbara Mannucci, Anna Cleta Croce, Vittoria Rizzo, Stefano Perlini, Mariapia Vairetti, Andrea Ferrigno

Abstract

We investigated changes in fatty acid desaturases, D5D, D6D, D9-16D and D9-18D, and their relationship with oxidative stress, matrix metalloproteinases (MMPs) and serum TNF-alpha in two rat models of non-alcoholic fatty liver disease NAFLD. Eight-week-old male Wistar rats fed for 3 weeks with methionine-choline⁻deficient (MCD) diet and eleven-week-old Obese male Zucker rats were used. Serum levels of hepatic enzymes and TNF-alpha were quantified. Hepatic oxidative stress (ROS, TBARS and GSH content) and MMP-2 and MMP-9 (protein expression and activity) were evaluated. Liver fatty acid profiling, performed by GC-MS, was used for the quantification of desaturase activities. Higher D5D and D9-16D were found in Obese Zucker rats as well as an increase in D9-18D in MCD rats. D6D was found only in MCD rats. A negative correlation between D5D and D9-16D versus TBARS, ROS and TNF-alpha and a positive correlation with GSH were shown in fatty livers besides a positive correlation between D9-18D versus TBARS, ROS and TNF-alpha and a negative correlation with GSH. A positive correlation between D5D or D9-16D or D9-18D versus protein expression and the activity of MMP-2 were found. NAFLD animal models showed comparable serum enzymes. These results reinforce and extend findings on the identification of therapeutic targets able to counteract NAFLD disorder.

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