The effects of high fat diet and moderate exercise on TGFβ1 and collagen deposition in mouse skeletal muscle

Obesity is a primary cause of muscle insulin resistance and is also associated with morphological and functional changes in the skeletal muscle including fibrosis. Studies suggest that macrophages in obese skeletal muscle may be primed to secrete transforming growth factor β1 (TGFβ1), a factor that can stimulate type I collagen gene expression via Smad3 activation but the extent to which exercise could modulate high fat (HF) diet-induced inflammation and fibrosis in skeletal muscle remains to be determined. The purpose of this study was to determine the extent to which moderate intensity exercise training can attenuate pro-inflammatory cytokine gene expression and markers of fibrosis in skeletal muscle in response to concomitant HF diet. Male C57BL/6J mice (6 wk old) were randomly assigned to one of four treatment groups: (1) Control diet-No Exercise (CON-No Ex), (2) CON-Ex, (3) HF-No Ex, or (4) HF-Ex. Mice were exercised on a motorized treadmill 40min/day at 12m/min, 5% grade, 5days/wk, for 12weeks. Macrophage (F4/80, CD11c, CD206), inflammatory cytokine (TNFα, IL-6, IL-10), TGFβ1, and collagen (Col1α) gene expression were evaluated in skeletal muscle by qPCR. Frozen muscle sections were stained to assess collagen content and fiber cross sectional area (CSA). F4/80, CD206 and IL-6 gene expression were increased by HF diet, and exercise only attenuated the increase in F4/80 and IL-6 (p<0.05). No differences in CD11c, TNFα and IL-10 gene expression were found between the groups. HF diet increased TGFβ1 protein expression, Smad3 activation, and collagen deposition in skeletal muscle, and exercise attenuated TGFβ1 protein expression and collagen deposition in skeletal muscle (p<0.05). Muscle fiber CSA was not different between the groups. The results from this study suggest that HF diet can increase skeletal muscle macrophage gene expression and fibrosis and that exercise can attenuate these changes.