Magic™ Anti-TRAP220/MED1 (Phospho T1457) polyclonal antibody

Peroxisome proliferator-activated receptor-alpha (PPAR alpha) modulates the activities of all three interlinked hepatic fatty acid oxidation systems, namely mitochondrial and peroxisomal beta-oxidation and microsomal omega-oxidation pathways. Hyperactivation of PPAR alpha, by both exogenous and endogenous activators up-regulates hepatic fatty acid oxidation resulting in excess energy burning in liver contributing to the development of liver cancer in rodents. Sustained PPAR alpha signaling disproportionately increases H2O2-generating fatty acid metabolizing enzymes as compared to H2O2-degrading enzymes in liver leading to enhanced generation of DNA damaging reactive oxygen species, progressive endoplasmic reticulum stress and inflammation. These alterations also contribute to increased liver cell proliferation with changes in apoptosis. Thus, reactive oxygen species, oxidative stress and hepatocellular proliferation are likely the main contributing factors in the pathogenesis of hepatocarcinogenesis, mediated by sustained PPAR alpha activation-related energy burning in liver. Furthermore, the transcriptional co-activator Med1, a key subunit of the Mediator complex, is essential for PPAR alpha signaling in that both PPAR alpha-null and Med1-null hepatocytes are unresponsive to PPAR alpha activators and fail to give rise to liver tumors when chronically exposed to PPAR alpha activators. (C) 2013 Elsevier Masson SAS. All rights reserved.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Increasing evidence has shown that microRNAs (miRNAs) play a vital role in the progression of NAFLD. The aim of the present study was to examine the expression level and roles of miR-146a in fatty liver of high-fat diet (HFD) and ob/ob mice and fatty acid-treated hepatic cells using RT-qPCR and western blot analysis. The results showed that the expression of miR-146a was significantly decreased in the livers of high-fat diet (HFD) and ob/ob mice and free fatty acid-stimulated cells by RT-qPCR. Overexpression of hepatic miR-146a improved glucose and insulin tolerance as well as lipid accumulation in the liver by promoting the oxidative metabolism of fatty acids. In addition, the overexpression of miR-146a increased the amount of mitochondria and promoted mitochondrial respiration in hepatocytes. Similarly, inhibition of miR-146a expression levels significantly reduced mitochondrial numbers in AML12 cells as well as the expression of mitochondrial respiration related genes. Additionally, MED1 was a direct target of miR-146a and restoring MED1 abolished the metabolic effects of miR-146a on lipid metabolism and mitochondrial function. Therefore, results of the present study identified a novel function of miR-146a in glucose and lipid metabolism in targeting MED1, suggesting that miR-146a serves as a potential therapeutic target for metabolic syndrome disease.