Exercise couples mitochondrial function with skeletal muscle fiber type via ROS-mediated epigenetic modification.

Skeletal muscle is a heterogeneous tissue composed of different types of muscle fibers, demonstrating substantial plasticity. Physiological or pathological stimuli can induce transitions in muscle fiber types. However, the precise regulatory mechanisms behind these transitions remains unclear. This paper reviews the classification and characteristics of muscle fibers, along with the classical mechanisms of muscle fiber type transitions. Additionally, the role of exercise-induced muscle fiber type transitions in disease intervention is reviewed. Epigenetic pathways mediate cellular adaptations and thus represent potential targets for regulating muscle fiber type transitions. This paper focuses on the mechanisms by which epigenetic modifications couple mitochondrial function and contraction characteristics. Reactive Oxygen Species (ROS) are critical signaling regulators for the health-promoting effects of exercise. Finally, we discuss the role of exercise-induced ROS in regulating epigenetic modifications and the transition of muscle fiber types.

Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.

Exercise training is considered a nonpharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete 4 wk of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial, and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimens need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.NEW & NOTEWORTHY This is the first study to investigate the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TDP-43 pathology and motor dysfunction, to perform exercise training. We demonstrate that despite the ALS-reminiscent aggressive disease progression characterizing the rNLS8 mouse model, rNLS8 mice are capable of performing mild-to-moderate endurance treadmill training for at least 3-4 wk. We demonstrate that exercise training induces several minor skeletal muscle adaptations without delaying disease progression in rNLS8 mice.

Dietary Malic Acid Supplementation Induces Skeletal Muscle Fiber-Type Transition of Weaned Piglets and Further Improves Meat Quality of Finishing Pigs.

The aim of this study was to investigate effects of dietary malic acid supplementation on skeletal muscle fiber-type transition during nursery period and the subsequent meat quality of finishing pigs. Results showed that malic acid supplementation for 28 days increased oxidative fiber percentage of weaned piglets, accompanied by the increased aerobic oxidation in serum and longissimus thoracis (LT) muscle. Additionally, activities of total antioxidant capacity and glutathione peroxidase in serum were increased. Moreover, dietary malic acid supplementation during nursery period tended to increase pH24h and significantly decreased drip loss in LT muscle of finishing pigs. The content of total saturated fatty acid (SFA) and total monounsaturated fatty acid in LT muscle was significantly decreased, whereas the ratio of polyunsaturated fatty acid to SFA tended to increase. Together, dietary malic acid supplementation during nursery period can effectively increase antioxidant capacity and oxidative fibers percentage of weaned piglets, and further improve water holding capacity and nutritional values of pork in finishing pigs.

Distinct Fiber Type Signature in Mouse Muscles Expressing a Mutant Lamin A Responsible for Congenital Muscular Dystrophy in a Patient.

Specific mutations in LMNA, which encodes nuclear intermediate filament proteins lamins A/C, affect skeletal muscle tissues. Early-onset LMNA myopathies reveal different alterations of muscle fibers, including fiber type disproportion or prominent dystrophic and/or inflammatory changes. Recently, we identified the p.R388P LMNA mutation as responsible for congenital muscular dystrophy (L-CMD) and lipodystrophy. Here, we asked whether viral-mediated expression of mutant lamin A in murine skeletal muscles would be a pertinent model to reveal specific muscle alterations. We found that the total amount and size of muscle fibers as well as the extent of either inflammation or muscle regeneration were similar to wildtype or mutant lamin A. In contrast, the amount of fast oxidative muscle fibers containing myosin heavy chain IIA was lower upon expression of mutant lamin A, in correlation with lower expression of genes encoding transcription factors MEF2C and MyoD. These data validate this in vivo model for highlighting distinct muscle phenotypes associated with different lamin contexts. Additionally, the data suggest that alteration of muscle fiber type identity may contribute to the mechanisms underlying physiopathology of L-CMD related to R388P mutant lamin A.