Effects of Aerobic Exercise Protocol on Genes Related to Insulin Resistance and Inflammation in the Pancreas of ob/ob Mice with NAFLD

Abstract

Purpose

To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD.

Materials and Methods

Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol^®. PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann–Whitney tests with Dunn’s post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher’s exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.).

Results

Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals.

Conclusion

An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.

Keywords:

• fatty liver
• exercise
• obese mice
• insulin resistance
• inflammation
• pancreas

Acknowledgments

We thank the Laboratory of Clinical and Experimental Gastroenterology (LIM-07), Laboratory of Transplantation and Liver Surgery (LIM-37) of the Department of Gastroenterology of the School of Medicine of the University of São Paulo (FMUSP) and Laboratory of Biomedicine of the School of Arts, Sciences and Humanities of USP (EACH-USP) in providing all structure and support for this study. This study was supported by grants from the Coordination of Improvement of Higher Level Personnel (CAPES).

Disclosure

The authors report no conflicts of interest in this work.