Metabolic Cooperation Between Adipose Tissue and Skeletal Muscle Mediates the Prevention of NAFLD Through Aerobic Physical Exercise.

Increased energy expenditure influences lipid handling by the liver. Aerobic exercise training (AET) has been widely used for the prevention and treatment of liver disorders especially non-alcoholic fatty liver disease (NAFLD). In the present study, we evaluated the contribution of visceral white and brown adipose tissue (WAT and BAT, respectively) and the skeletal muscle to prevent NAFLD through aerobic physical exercise (APE). Adult male C57BL6/J mice were assigned into groups (n=10/group): chow-fed controls (C), chow-fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). AET was performed simultaneously with diet and consisted of 8-wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (002/2015) and from School of Arts, Science and Humanities, University of Sao Paulo (002/2018). The CAF group presented higher body weight gain, glucose intolerance, insulin resistance while AET prevented such damages in the CAFT group. In the liver, lipid deposition was higher in CAF (10.7 ± 1.9 %/area) compared to C, T and CAFT groups (6.4 ± 1.4, 0.5 ± 0.2 and 5.3 ± 1.1 %/area, respectively), the protein expression of DGAT2 did not differ but the expression of FAS enzyme and the content of IL-6 was lower in CAFT compared to CAF. The CAF group increased periepididymal WAT weight compared to C and T groups, and the protein expressions of p-HSL and ATGL, which are markers of lipolysis, increased in both CAF and CAFT compared to C and T groups. In addition, interscapular BAT weight did not change among groups, however the protein expression of UCP1 and PGC1a, which are markers of thermogenesis, increased in both CAF and CAFT compared to C and T groups. The activity of oxidative enzymes citrate synthase and β-HAD in the soleus muscle increased in the T (352 ± 21.5 and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 and 46.7 ± 1.6 mmol/min/mg) groups. In conclusion, for the prevention of NAFLD, the AET increased the metabolic activation of WAT and BAT that favors fat oxidation as well as improved the oxidative capacity of skeletal muscle to deal with excess lipids.