PPARα protects against trans-fatty-acid-containing diet-induced steatohepatitis

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• 作者：Xiao Hu^a ; Naoki Tanaka^a ; ^{naopi@shinshu-u.ac.jp} ; Ran Guo^a ; Yu Lu^a ; Takero Nakajima^a ; Frank J. Gonzalez^b ; Toshifumi Aoyama^a
• 关键词：ACCα ; acetyl-CoA carboxylase α ; ALT ; alanine aminotransferase ; ATGL ; adipose triglyceride lipase ; CoA ; coenzyme A ; ER ; endoplasmic reticulum ; FA ; fatty acid ; FABP1 ; FA-binding protein 1 ; FAS ; FA synthase ; IL ; interleukin ; LACS ; long-chain acyl-CoA synthase ; LCAD ; long-chain acyl-CoA dehydrogenase ; MCP1 ; monocyte chemoattractant protein 1 ; MTP ; microsomal TG transfer protein ; NAFLD ; non-alcoholic fatty liver disease ; NASH ; non-alcoholic steatohepatitis ; NF-κB ; nuclear factor-kappa B ; OPN ; osteopo
• 刊名：The Journal of Nutritional Biochemistry
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：39
• 期：Complete
• 页码：77-85
• 全文大小：1620 K
• 卷排序：39

文摘

Consumption of trans-fatty acids (TFA), unsaturated fatty acids (FA) containing trans double bonds, is a risk factor for metabolic syndrome and steatohepatitis. Peroxisome proliferator-activated receptor α (PPARα) is a master regulator of hepatic lipid homeostasis. To examine the contribution of PPARα to changes in liver phenotypes induced by TFA, two diets were used: a purified control diet and an isocaloric diet in which most of the soybean oil, a major source of FA in the diet, was replaced with TFA-rich shortening. The diets were fed to wild-type and Ppara-null mice for 2 months. Ppara-null mice fed a TFA-containing diet showed more severe hepatic steatosis and liver damage compared with similarly treated wild-type mice, as revealed by increased hepatic triglyceride (TG) contents and serum alanine aminotransferase activities. While the TFA-rich diet increased the hepatic expression of enzymes involved in de novo FA synthesis and decreased TG-hydrolyzing enzymes in both genotypes, the expression of FA-catabolizing enzymes was decreased in Ppara-null mice, resulting in more severe hepatosteatosis. Additionally, the expression levels of key contributors to inflammation, such as osteopontin, were increased, and nuclear factor-kappa B was activated in TFA-containing diet-fed Ppara-null mice. Enhanced inflammatory signaling in these mice was presumably mediated by toll-like receptor 2, with no accompanying inflammasome activation. Collectively, these results suggest a protective role for PPARα in the pathological changes in the liver following TFA consumption. PPARα might prevent TFA-containing diet-induced steatohepatitis.