Effects of Porcine Whole-Blood Protein Hydrolysate on Exercise Function and Skeletal Muscle Differentiation

A number of studies have utilized blood waste as a bioresource by enzymatic hydrolysis to obtain amino acids, such as branched-chain amino acids, which can increase muscle mass or prevent muscle loss during weight loss. Although a significantly high content of branched-chain amino acids has been reported in porcine whole-blood protein hydrolysate (PWBPH), the effects of PWBPH on skeletal muscle differentiation and exercise function remain unclear. In this study, we investigated the effects of PWBPH on exercise endurance in ICR mice and muscle differentiation in C2C12 mouse myoblasts and gastrocnemius (Gas) muscle of mice. Supplementation with PWBPH (250 and 500 mg/kg for 5 weeks) increased the time to exhaustion on a treadmill. PWBPH also increased the Gas muscle weight to body weight ratio. In addition, PWBPH treatment increased skeletal muscle differentiation proteins and promoted the Akt/mTOR-dependent signaling pathway in vitro and in vivo. These results suggest that PWBPH can be utilized as a bioresource to enhance exercise function and skeletal muscle differentiation.

Evaluation of muscle-specific and metabolism regulating microRNAs in a chronic swimming rat model

Making benefit from the epigenetic effects of environmental factors such as physical activity may result in a considerable improvement in the prevention of chronic civilization diseases. In our chronic swimming rat model, the expression levels of such microRNAs were characterized, that are involved in skeletal muscle differentiation, hypertrophy and fine-tuning of metabolism, which processes are influenced by chronic endurance training, contributing to the metabolic adaptation of skeletal muscle during physical activity. After chronic swimming, the level of miR-128a increased significantly in EDL muscles, which may influence metabolic adaptation and stress response as well. In SOL, the expression level of miR-15b and miR-451 decreased significantly after chronic swimming, which changes are opposite to their previously described increment in insulin resistant skeletal muscle. MiR-451 also targets PGC-1α mRNA, whiches expression level significantly increased in SOL muscles, resulting in enhanced biogenesis and oxidative capacity of mitochondria. In summary, the microRNA expression changes that were observed during our experiments suggest that chronic swim training contributes to a beneficial metabolic profile of skeletal muscle.

TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake

TNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation. The aim of the present work was to evaluate TRAIL actions on skeletal muscle. Our in vitro data on C2C12 cells showed that TRAIL treatment significantly increased myogenin and MyHC and other hallmarks of myogenic differentiation, which were reduced by Dr5 (TRAIL receptor) silencing. In addition, TRAIL treatment significantly increased AKT phosphorylation, which was reduced by Dr5 silencing, as well as glucose uptake (alone and in combination with insulin). Our in vivo data showed that TRAIL increased myofiber size in HFD-fed mice as well as in db/db mice. This was associated with increased myogenin and PCG1α expression. In conclusion, TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake. These data shed light onto a pathway that might hold therapeutic potential not only for the metabolic disturbances but also for the muscle mass loss that are associated with diabetes.

MicroRNA-24-3p promotes skeletal muscle differentiation and regeneration by regulating HMGA1

Numerous studies have established the critical roles of microRNAs in regulating posttranscriptional gene expression in diverse biological processes. Here, we report on the role and mechanism of miR-24-3p in skeletal muscle differentiation and regeneration. miR-24-3p promotes myoblast differentiation and skeletal muscle regeneration by directly targeting high mobility group AT-hook 1 (HMGA1) and regulating it and its direct downstream target, the inhibitor of differentiation 3 (ID3). miR-24-3p knockdown in neonatal mice increases PAX7-positive proliferating muscle stem cells (MuSCs) by derepressing Hmga1 and Id3 . Similarly, inhibiting miR24-3p in the tibialis anterior muscle prevents Hmga1 and Id3 downregulation and impairs regeneration. These findings provide evidence that the miR-24-3p/HMGA1/ID3 axis is required for MuSC differentiation and regeneration in vivo .