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

Author(s)

Batatinha, Helena A. P. ; Lima, Edson A. ; Teixeira, Alexandre A. S. ; Souza, Camila O. ; Biondo, Luana A. ; Silveira, Loreana S. ; Lira, Fabio S. ; Rosa Neto, Jose C.

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 232, n. 5, p. 1008-1019, MAY 2017.
• Web of Science Citations: 9

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 PPAR alpha is involved in these actions. C57BL6 wild type (WT) and PPAR-alpha 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-gamma expression. We conclude that exercise improved the damage caused by a HF independently of PPAR alpha, apparently by a peripheral fatty acid oxidation in the skeletal muscle. We also found that the absence of PPAR alpha together with exercise leads to a decrease in PPAR-gamma and a huge inflammatory response. (C) 2016 Wiley Periodicals, Inc. (AU)

• FAPESP's process: 13/09367-4 - Metabolic effects of doxorubicin on the muscle and adipose tissue: do exercise and metformin reduce the damage?
• Grantee: José Cesar Rosa Neto
• Support type: Regular Research Grants
• FAPESP's process: 14/01246-6 - Evaluation of immune metabolic response in peritoneal macrophages from obese mice: role of physical exercise and PPAR-gamma
• Grantee: Loreana Sanches Silveira
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/25310-2 - Evaluation of immune-metabolic blood cells in obese subjects: role of physical exercise and PPAR-gamma
• Grantee: Fábio Santos de Lira
• Support type: Regular Research Grants