Abstract
Muscle dysfunction is a complication of high-fat diet (HFD)-induced obesity that could be prevented by exercise, but patients did not get enough therapeutic efficacy from exercise due to multiple reasons. To explore alternative or supplementary approaches to prevent or treat muscle dysfunction in individuals with obesity, we investigated the effects of Rhodiola on muscle dysfunction as exercise pills. SIRT1 might suppress atrogenes expression and improve mitochondrial quality control, which could be a therapeutic target stimulated by exercise and Rhodiola, but further mechanisms remain unclear. We verified the lipid metabolism disorders and skeletal muscle dysfunction in HFD feeding mice. Moreover, exercise and Rhodiola were used to intervene mice with a HFD. Our results showed that exercise and Rhodiola prevented muscle atrophy and dysfunction in obese mice and activating the SIRT1 pathway, while atrogenes were suppressed and mitochondrial quality control was improved. EX-527, SIRT1 inhibitor, was used to validate the essential role of SIRT1 in salidroside benefit. Results of cell culture experiment showed that salidroside alleviated high palmitate-induced atrophy and mitochondrial quality control impairments, but these improvements of salidroside were inhibited by EX-527 in C2C12 myotubes. Overall, Rhodiola mimics exercise that activates SIRT1 signaling leading to improvement of HFD-induced muscle dysfunction.
Highlights
Skeletal muscle dysfunction characterized with a reduction of myofibrillar, and mitochondrial dysfunction has been reported as an important complication of high-fat diet (HFD)induced obesity (Perry et al, 2016)
In our present study, following HFD feeding for 8 weeks, mouse body weights increased more profound than normal chow group (Figure 2A)
We found that Sirtuin 1 (SIRT1) protein levels were significantly decreased in skeletal muscle following HFD feeding, and this reduction was inhibited by exercise training or R. sacra treatment (Figure 4A)
Summary
Skeletal muscle dysfunction (or muscle wasting) characterized with a reduction of myofibrillar, and mitochondrial dysfunction has been reported as an important complication of high-fat diet (HFD)induced obesity (Perry et al, 2016). Investigating the mechanisms and potential therapy against HFD-induced muscle dysfunction will have important clinical significance. The molecular mechanisms of exercise in regulating HFD-induced muscle dysfunction are largely unknown, previous evidence indicated that exercise could decrease transcription of atrogenes, such as musclespecific RING finger protein 1 (MuRF1) and atrogin, both of which inhibit protein degradation and facilitate myofibrillar synthesis. Our previous studies indicated that exercise activates MQC in skeletal and myocardial muscle (Xie et al, 2019; Jiang et al, 2021). Alternative or supplementary approaches to prevent muscle dysfunction in individuals with overweight need to be explored
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