Abstract
The effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation associated with exercise training at different intensities and frequencies on skeletal muscle regeneration of muscle-injured rats was investigated. Male Wistar rats were divided into sedentary and trained groups. The sedentary groups were subdivided into non-injured (SED-Ct), non-injured supplemented with HMB (SED-Ct-HMB), injured (SED), and injured with HMB (SED-HMB), and the trained groups were injured, supplemented with HMB, and then divided into training three times a week without load (HT3) or with load (HT3L) and training five times a week without load (HT5) and with load (HT5L). The rats received a daily dose of HMB associated with 60 min of swimming with or without 5% body mass load for 14 days. On the 15th day, cryoinjury was performed in the right tibialis anterior muscle (TA), and 48 h later, supplementation and training continued for 15 days. After the last session, the TA was dissected and a cross-sectional area (CSA) of muscle fibers was used to determine the percentage of CSA fibers and connective tissue (%CT), as well as the total and phosphorylated protein contents. SED-HMB showed increased CSA and decreased %CT and TGF-β when compared to SED. HT3 showed increased CSA and reduced %CT accompanied by increased IGF-1/Akt, myogenin, and MuRF1, and decreased TGF-β. The CSA of HT5L also increased, but at the cost of a higher %CT compared to the other groups. Our results demonstrated that HMB associated with training without load and with lower frequency per week may be a valuable strategy for skeletal muscle regeneration.
Highlights
Skeletal muscle is a plastic tissue with exceptional regenerative capacity; only a few weeks after a severe injury that destroys fiber integrity, the structure and function of skeletal muscle can be completely restored [1]
The left tibialis anterior muscle (TA) muscles were used as a control for the right TA muscles, forming four groups: i) non-injured sedentary control (Sed-Ct); ii) non-injured sedentary control supplemented with HMB (Sed-Ct-HMB); iii) injured sedentary with normal diet (Sed); and iv) injured sedentary supplemented with HMB (Sed-HMB; Figure 1A and B)
The normalized GAPDH protein level of MuRF was significantly decreased in all groups compared to the HT3 group (Figure 5J), the protein level of GDF8 was significantly increased in the HT3 group compared to the HT5 group (Figure 5G). This was the first study to investigate the combination of HMB and different intensities of aerobic exercise training in the regeneration of skeletal muscle injuries in rats
Summary
Skeletal muscle is a plastic tissue with exceptional regenerative capacity; only a few weeks after a severe injury that destroys fiber integrity, the structure and function of skeletal muscle can be completely restored [1]. Nutritional supplements have been widely investigated for their role in muscle regeneration [3,4], such as betahydroxy-beta-methylbutyrate (HMB), a metabolite of the amino acid leucine that increases the anabolic properties of protein synthesis in skeletal muscle [5] through the mammalian target of rapamycin (mTOR) pathway. This occurs via downstream p70S6 kinase (p70S6K) and decreases protein degradation through the ubiquitinproteasome system [6]. We can expect a potentiating effect of HMB in skeletal
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