Costly immunometabolic remodelling in disused muscle buildup through physical exercise

Abstract

The mechanisms underlying the immunometabolic disturbances during skeletal muscle atrophy caused by a plethora of circumstances ranging from hospitalization to spaceflight missions remain unknown. Here, we outline the possible pathways that might be dysregulated in such conditions and assess the potential of physical exercise to mitigate and promote the recovery of muscle morphology, metabolism and function after intervals of disuse. Studies applying exercise to attenuate disuse‐induced muscle atrophy have shown a pivotal role of circulating myokines in the activation of anabolic signalling pathways. These muscle‐derived factors induce accretion of contractile proteins in the myofibers, and at the same time decrease protein breakdown and loss. Regular exercise plays a crucial role in re‐establishing adequate immunometabolism and increasing the migration and presence in the muscle of macrophages with an anti‐inflammatory phenotype (M2) and T regulatory cells (Tregs) after disease‐induced muscle loss. Additionally, the switch in metabolic pathways (glycolysis to oxidative phosphorylation [OXPHOS]) is important for achieving rapid metabolic homeostasis during muscle regeneration. In this review, we discuss the molecular aspects of the immunometabolic response elicited by exercise during skeletal muscle regeneration. There is not, nevertheless, consensus on a single optimal intensity of exercise required to improve muscle strength, mass and functional capacity owing to the wide range of exercise protocols studied so far. Despite the absence of agreement on the specific strategy, physical exercise appears as a powerful complementary strategy to attenuate the harmful effects of muscle disuse in different scenarios.

Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions

“…These were the two SDM-associated pathways, necroptosis, GP6 signaling, and the four LDM-associated pathways, fatty acid β-oxidation, ILK, RHO, and dilated cardiomyopathy signaling that characterize metabolic SOL muscle changes in short vs. long duration mission conditions in spaceflight. Apart from TCA cycle inhibition found under both SDM or LDM conditions, oxidative phosphorylation pathway proteins, most of them known as molecular markers of mitochondrial response in muscle wasting and other disuse scenarios [ 23 ], as well as in physical exercise [ 24 ], almost recovered following LDM vs. SDM as most likely a signature of inflight CM exercise benefit for the slow-type myofiber-containing SOL during LDM spaceflight. By contrast, the SDM-associated change in necroptosis signaling pathway-associated proteins are known signatures associated to muscle weakness and wasting [ 25 ], autophagy/mitophagy [ 25 , 26 , 27 ], or even aging [ 28 ] in disuse conditions or muscle disease.…”

New insights into the molecular basis of how physical activity contributes to human health

“…In their review, Padilha et al focus on the question how physical exercise promotes immunometabolism in disused muscles, for example, because of bed rest or space flight. 12 Immunometabolic changes in muscle due to disuse refer to responses from macrophages and T cells in tissues and further circulating immune cells and pro-inflammatory cytokines. After physical exercise following an interval of disuse, an arsenal of M2 macrophages, Treg cells, anti-inflammatory cytokines, and catecholamines contribute to protein synthesis for muscle remodeling.…”

“…However, the authors emphasize the participation of hospitalized patients and astronauts in exercise programs to counteract negative immunometabolic responses. 12 Besides immune responses, endocrine organs regulate major systemic impacts resulting from exercise. Tissue cross talk takes place via known potential mediators, which are called exerkines.…”

Exercise and energy

“…8 Another interesting publication has studied, in detail, the mechanism and energetic costs of rebuilding muscle following immobilization. 10 Another concept that has only rather recently been investigated in relation to exercise is autophagy: The positive modulating effect of exercise on autophagy seems to mediate the cardiovascular protective mechanisms of exercise. 11 Studies of athletic rather than regenerative or therapeutic exercise often focus on the ergogenic mechanisms that enable high performance.…”

“…Interestingly, it is not always and only the mother who counts, and the potential preventive strategies resulting from these insights are of great value for the early prevention of metabolic disease 8 . Another interesting publication has studied, in detail, the mechanism and energetic costs of rebuilding muscle following immobilization 10 . Another concept that has only rather recently been investigated in relation to exercise is autophagy: The positive modulating effect of exercise on autophagy seems to mediate the cardiovascular protective mechanisms of exercise 11 …”