Effect of Training Intensity on Hepatic Steatosis and Expression of miRNAs and Target Genes in a High-fat Diet-induced Mice

Abstract

PURPOSE This study investigated the effect of exercise intensity on hepatic microRNA (miRNA) expression in a high-fat diet (HFD)-induced obese mice. METHODS A total of 40 male C57BL/6 mice aged 5 weeks were randomly subjected to either standard chow (SC, n = 10) or HFD (HFD, n = 30) for 23 weeks. After 8 weeks of dietary treatments, mice in the HFD group were further divided and subjected to either HFD only (n = 10) or HFD with high-intensity interval treadmill running (HFD+INT, n = 10) or HFD with moderate-intensity treadmill running (HFD+MOD) for additional 15 weeks. Hepatic total RNA was extracted to analyze global expression profiles of miRNAs, which was followed by real-time PCR to quantify hepatic expressions of up or down-regulated miRNAs and mRNAs. RESULTS As expected, chronic exposure to HFD resulted in obesity and hepatic steatosis in conjunction with increased serum concentrations of total cholesterol, aspartate transaminase, and alanine transaminase. In addition, HFD resulted in upregulation of hepatic miR-149 and miR-34a levels in conjunction with downregulation of hepatic peroxisome proliferator-activated receptor alpha (PPAR-α) and sirtuin1 (SIRT1) mRNAs. On the other hand, exercise training, especially high-intensity interval training, attenuated the liver damage and total cholesterol in conjunction with downregulation of hepatic miR-149 and miR-34a levels and upregulation of hepatic PPAR-α and SIRT1 mRNAs. CONCLUSIONS This study suggests that exercise training, especially performed at a high-intensity, was effective in attenuating HFD-induced-fatty liver phenotypes as well as HFD–induced dysregulation of miRNAs in the liver.

Keywords

• non-alcoholic fatty liver
• exercise intensity
• microrna
• treadmill running