Exercise attenuates angiotensinII-induced muscle atrophy by targeting PPARy/miR-29b

Background: Exercise is beneficial for muscle atrophy. Peroxisome proliferator-activated receptor gamma (PPARy) and microRNA-29b (miR-29b) have been reported to be responsible for angiotensinII (AngII)-induced muscle atrophy. However, it is unclear whether exercise can protect AngII-induced muscle atrophy by targeting PPARy/miR-29b.Methods: Skeletal muscle atrophy in both the control group and the run group was established by AngII infusion; after 1 week of exercise train-ing, the mice were sacrificed, and muscle weight was determined. Myofiber size was measured by hematoxylin-eosin and wheat-germ agglutinin staining. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression level of muscle atrogenes, including F-box only protein 32 (FBXO32, also called Atrogin-1) and muscle-specific RING-finger 1 (MuRF-1), the phosphorylation level of protein kinase B (PKB, also called AKT)/forkhead box O3A (FOXO3A)/mammalian target of rapamycin (mTOR) pathway proteins, the expression level of PPARy and apoptosis-related proteins, including B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteine-aspartic acid protease 3 (caspase-3), and cleaved-caspase-3, were determined by western blot. The expression level of miR-29b was checked by reverse -transcription quantitative polymerase chain reaction. A PPARy inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression was used to demonstrate whether PPARy activation or miR-29b inhibition mediates the beneficial effects of exercise in AngII-induced muscle atrophy.Results: Exercise can significantly attenuate AngII-induced muscle atrophy, which is demonstrated by increased skeletal muscle weight, cross-sectional area of myofiber, and activation of AKT/mTOR signaling and by decreased atrogenes expressions and apoptosis. In AngII-induced muscle atrophy mice models, PPARy was elevated whereas miR-29b was decreased by exercise. The protective effects of exercise in AngII-induced muscle atrophy were inhibited by a PPARy inhibitor (T0070907) or adeno-associated virus serotype-8 (AAV8)-mediated miR-29b overexpression.Conclusion: Exercise attenuates AngII-induced muscle atrophy by activation of PPARy and suppression of miR-29b.

Automated summary

Exercise attenuates AngII-induced muscle atrophy by activation of PPARy and suppression of miR-29b.