The effect of caloric restriction on the forelimb skeletal muscle fibers of the hypertrophic myostatin null mice

Abstract

Skeletal muscle mass loss has a broad impact on body performance and physical activity. Muscle wasting occurs due to genetic mutation as in muscular dystrophy, age-related muscle loss (sarcopenia) as well as in chronic wasting disorders as in cancer cachexia. Food restriction reduces muscle mass underpinned by increased muscle protein break down. However the influence of dietary restriction on the morphometry and phenotype of forelimb muscles in a genetically modified myostatin null mice are not fully characterized. The effect of a five week dietary limitation on five anatomically and structurally different forelimb muscles was examined. C57/BL6 wild type (Mstn) and myostatin null (Mstn) mice were either given a standard rodent normal daily diet ad libitum (ND) or 60% food restriction (FR) for a 5 week period. M. triceps brachii Caput laterale (T.lateral), M. triceps brachii Caput longum (T.long), M. triceps brachii Caput mediale (T.medial), M. extensor carpi ulnaris (ECU) and M. flexor carpi ulnaris (FCU) were dissected, weighted and processed for immunohistochemistry. Muscle mass, fibers cross sectional areas (CSA) and myosin heavy chain types IIB, IIX, IIA and type I were analyzed. We provide evidence that caloric restriction results in muscle specific weight reduction with the fast myofibers being more prone to atrophy. We show that slow fibers are less liable to dietary restriction induced muscle atrophy. The effect of dietary restriction was more pronounced in Mstn muscles to implicate the oxidative fibers compared to Mstn. Furthermore, peripherally located myofibers are more susceptible to dietary induced reduction compared to deep fibers. We additionally report that dietary restriction alters the glycolytic phenotype of the Mstn into the oxidative form in a muscle dependent manner. In summary our study shows that calorie restriction alters muscle fiber profile of forelimb muscles of Myostatin null mice.

The effect of high‐fat diet on the morphological properties of the forelimb musculature in hypertrophic myostatin null mice

“…Although the deletion of myostatin results in an increase in the number of muscle fibers, as previously shown (McPherron & Lee, ; Elashry et al. , ), there was no alteration in fiber number after HFD for 10 weeks, which excludes not only the possibility of myofiber hyperplasia but also myofiber apoptosis/loss due to lipotoxicity. In agreement with our results, a study demonstrated that HFD intake for up to 16 weeks failed to induce autophagy or even apoptosis in soleus and plantaris muscles of rat (Campbell et al.…”

“…) as well as to atrophy after 5 weeks of dietary restriction (Elashry et al. ). The results suggest a compensatory mechanism to maximize energy utilization in the course of the HFD regimen by either reducing the size of the fast MHC fibers or by increasing the size of the slow fiber isoform.…”

Resveratrol treatment reduces the appearance of tubular aggregates and improves the resistance to fatigue in aging mice skeletal muscles

“…This observation can be explained by a general decrease of the CSA regardless the different MyHC expressed. In this context, the CSA decrease was recently reported as an effect of a caloric restriction regimen (Elashry et al, 2017). It can be proposed that RES, as a caloric restriction mimetic, most probably reduces the CSA maintaining higher levels of MyHCIIB.…”