Association Between Aerobic Exercise and Rosiglitazone Avoided the NAFLD and Liver Inflammation Exacerbated in PPAR‐α Knockout Mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases today, and may progress to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Some studies have shown the beneficial effects of aerobic exercise on reversing NAFLD. To verify whether chronic aerobic exercise improves the insulin resistance, liver inflammation, and steatohepatitis caused by a high fat diet (HF) and whether PPARα is involved in these actions. C57BL6 wild type (WT) and PPAR-α knockout (KO) mice were fed with a standard diet (SD) or HF during 12 weeks; the HF mice were trained on a treadmill during the last 8 weeks. Serum glucose and insulin tolerances, serum levels of aspartate aminotransferase, hepatic content of triacylglycerol, cytokines, gene expression, and protein expression were evaluated in all animals. Chronic exposure to HF diet increased triacylglycerol accumulation in the liver, leading to NAFLD, increased aminotransferase in the serum, increased peripheral insulin resistance, and higher adiposity index. Exercise reduced all these parameters in both animal genotypes. The liver lipid accumulation was not associated with inflammation; trained KO mice, however, presented a huge inflammatory response that was probably caused by a decrease in PPAR-γ expression. We conclude that exercise improved the damage caused by a HF independently of PPARα, apparently by a peripheral fatty acid oxidation in the skeletal muscle. We also found that the absence of PPARα together with exercise leads to a decrease in PPAR-γ and a huge inflammatory response. J. Cell. Physiol. 232: 1008-1019, 2017. © 2016 Wiley Periodicals, Inc.

Effect of an acute moderate‐exercise session on metabolic and inflammatory profile of PPAR‐α knockout mice

“…The roles of PPAR‐α on metabolism are well known, although the acute exercise‐mediated aspects that could regulate these transcriptional factors are a field that has not been deeply explored. Nonetheless, a few studies involving exercise have investigated the modulation of PPAR gene expression in several tissues . Therefore, the aim of the present study was to understand the influence of PPAR‐α on exercise‐mediated metabolic profile variations, as well as cytokine production and gene expression in peritoneal macrophages.…”

“…Nonetheless, a few studies involving exercise have investigated the modulation of PPAR gene expression in several tissues. [10][11][12] Therefore, the aim of the present study was to understand the influence of PPAR-α on exercise-mediated metabolic profile variations, as well as cytokine production and gene expression in peritoneal macrophages.…”

A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets

“…In previous studies, PPARα may mediate NAFLD through a periostin-dependent pathway. It can regulate fatty acid oxidation by activating the periostin-dependent JNK signaling pathway and further activate hepatosteatosis in vivo and in vitro [33,34,35]. Activation of PPARα is also associated with increased mitochondrial glutathione (GSH) in the liver and decreased levels of circulating fatty acyl-carnitines [36].…”

“…Chemical ingredients of Danshen were manually collected from related literature and two phytochemical databases: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) (Available online: ) and TCM Database@Taiwan (Available online: ) [31,32,33,34,35,36]. …”

PPAR-γ activation restores liver inflammation after chronic exercise in PPAR-α knockout obese mice

“…PPAR-γ plays key anti-inflammatory role decreasing NF-κB activity and promoting M2 macrophages polarization, whereas PPAR-α acts modulating the transcription of enzymes involved in β-oxidation, favoring fatty acid oxidation (2) . Obese PPAR-α knockout (KO) mice exhibit low liver lipid accumulation but increases liver inflammation when trained, followed by a reduction in PPAR-γ protein and gene expression (3) .…”