The aim of the present study was to evaluate the effect of both swimming and resistance training on tumor necrosis factor-alpha and interleukin-10 expression, adipocyte area and lipid profiles in rats fed a high-fat diet. The study was conducted over an eight-week period on Wistar adult rats, who were divided into six groups as follows (n = 10 per group): sedentary chow diet, sedentary high-fat diet, swimming plus chow diet, swimming plus high-fat diet, resistance training plus chow diet, and resistance training plus high-fat diet. Rats in the resistance training groups climbed a vertical ladder with weights on their tails once every three days. The swimming groups swam for 60 minutes/day, five days/week. The high-fat diet groups had higher body weights, a greater amount of adipose tissue, and higher tumor necrosis factor-alpha expression in the visceral adipose tissue. Furthermore, the high-fat diet promoted a negative change in the lipid profile. In the resistance training high-fat group, the tumor necrosis factor-alpha expression was lower than that in the swimming high-fat and sedentary high-fat groups. Moreover, smaller visceral and retroperitoneal adipocyte areas were found in the resistance training high-fat group than in the sedentary high-fat group. In the swimming high-fat group, the tumor necrosis factor-alpha expression was lower and the epididymal and retroperitoneal adipocyte areas were smaller compared with the sedentary high-fat group. The results showed that both exercise modalities improved the lipid profile, adiposity and obesity-associated inflammation in rats, suggesting their use as an alternative to control the deleterious effects of a high-fat diet in humans.

Aim To Identify microRNAs (miRs) involved in the regulation of skeletal muscle mass. For that purpose, we have initially utilized an in silico analysis, resulting in the identification of miR‐29c as a positive regulator of muscle mass. Methods miR‐29c was electrotransferred to the tibialis anterior to address its morphometric and functional properties and to determine the level of satellite cell proliferation and differentiation. qPCR was used to investigate the effect of miR‐29c overexpression on trophicity‐related genes. C2C12 cells were used to determine the impact of miR‐29c on myogenesis and a luciferase reporter assay was used to evaluate the ability of miR‐29c to bind to the MuRF1 3’UTR. Results The overexpression of miR‐29c in the tibialis anterior increased muscle mass by 40%, with a corresponding increase in fiber cross‐sectional area and force and a 30% increase in length. In addition, satellite cell proliferation and differentiation were increased. In C2C12 cells, miR‐29c oligonucleotides caused increased levels of differentiation, as evidenced by an increase in eMHC immunostaining and the myotube fusion index. Accordingly, the mRNA levels of myogenic markers were also increased. Mechanistically, the overexpression of miR‐29c inhibited the expression of the muscle atrophic factors MuRF1, Atrogin‐1, and HDAC4. For the key atrogene MuRF1, we found that miR‐29c can bind to its 3’UTR to mediate repression. Conclusions The results herein suggest that miR‐29c can improve skeletal muscle size and function by stimulating satellite cell proliferation and repressing atrophy‐related genes. Taken together, our results indicate that miR‐29c might be useful as a future therapeutic device in diseases involving decreased skeletal muscle mass.

Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of sarcopenic obesity. Herein, we chose two non-cytotoxic concentrations to better understand how excess PA could impact myotube formation or diameter without inducing cell death. Forty-eight hours of 100 µM PA induced a reduction of myotube diameter and increased the number of type I fibers, which was associated with increased miR-206 expression. Next, C2C12 myotube growth in the presence of PA was evaluated. Compared to control cells, 150 µM PA reduces myoblast proliferation and the expression of MyoD and miR-206 and miR-133a expression, leading to a reduced number and diameter of myotubes. PA (100 µM), despite not affecting proliferation, impairs myotube formation by reducing the expression of Myf5 and miR-206 and decreasing protein synthesis. Interestingly, 100 and 150 µM PA-treated myotubes had a higher number of type II fibers than control cells. In conclusion, PA affects negatively myotube diameter, fusion, and metabolism, which may be related to myomiRs. By providing new insights into the mechanisms by which PA affects negatively skeletal muscle, our data may help in the discovery of new targets to treat sarcopenic obesity.

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin^–/–) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin^–/– mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin^–/– mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation.

Tribbles 3 (TRB3) is a pseudokinase that has been found in multiple tissues in response to various stress stimuli, such as nutrient deprivation and endoplasmic reticulum (ER) stress. We recently found that TRB3 has the potential to regulate skeletal muscle mass at the basal state. However, it has not yet been explored whether TRB3 regulates skeletal muscle mass under atrophic conditions. Here, we report that food deprivation for 48 h in mice significantly reduces muscle mass by ∼15% and increases TRB3 expression, which is associated with increased ER stress. Interestingly, inhibition of ER stress in C2C12 myotubes reduces food deprivation–induced expression of TRB3 and muscle‐specific E3‐ubiquitin ligases. In further in vivo experiments, muscle‐specific TRB3 transgenic mice increase food deprivation–induced muscle atrophy compared with wild‐type (WT) littermates presumably by the increased proteolysis. On the other hand, TRB3 knockout mice ameliorate food deprivation–induced atrophy compared with WT littermates by preserving a higher protein synthesis rate. These results indicate that TRB3 plays a pivotal role in skeletal muscle mass regulation under food deprivation–induced muscle atrophy and TRB3 could be a pharmaceutical target to prevent skeletal muscle atrophy.—Choi, R. H., McConahay, A., Silvestre, J. G., Moriscot, A. S., Carson, J. A., Koh, H.‐J. TRB3 regulates skeletal muscle mass in food deprivation–induced atrophy. FASEB J. 33, 5654–5666 (2019). www.fasebj.org