Dietary restriction and aerobic exercise alleviate obesity-related skeletal muscle impairment via the miR-130/PPARγ axis and IGF-1/Akt/mTOR signaling activation

This study investigated the effects of dietary restriction (DR) combined with aerobic exercise training (ET) on high-fat diet (HFD)-induced obesity and associated skeletal muscle impairment in male Sprague-Dawley rats, as well as the underlying mechanisms. An 8-week DR + ET intervention effectively increased the cross-sectional area and protein content of the soleus muscle. Both DR and ET alone promoted the activation of the IGF-1/Akt/mTOR signaling pathway and reduced the protein expression of peroxisome proliferator-activated receptor γ (PPARγ), a target of miR-130 in adipocytes, in HFD-induced obese rats. However, no additional benefit was observed with combined DR + ET treatment. Consistent with these findings, miR-130 expression was upregulated in the skeletal muscle of obese rats compared with those fed a normal diet, and this increase was significantly attenuated by DR, ET, or DR + ET, with DR + ET showing the strongest inhibitory effect. To further explore the role of miR-130 in skeletal muscle cells, L6 and C2C12 cells were transfected with miR-130 mimics. Overexpression of miR-130 markedly suppressed proliferation and differentiation in these cells, accompanied by reduced creatine kinase activity and decreased myogenin expression—both key markers of myogenic differentiation. Moreover, miR-130 overexpression inhibited the luciferase activity of a reporter vector containing the PPARγ-3′-UTR, and this inhibition was abolished by mutation of the PPARγ-3′-UTR, indicating a direct regulatory mechanism affecting protein synthesis in skeletal muscle. In summary, DR and ET each alleviated obesity-related skeletal muscle impairment by activating IGF-1/Akt/mTOR signaling and suppressing miR-130 expression, but their combination did not produce synergistic effects.