COVID-19, a disease caused by the novel coronavirus SARS-CoV-2, has been drastically affecting the daily lives of millions of people. COVID-19 is described as a multiorgan disease that affects not only the respiratory tract of infected individuals, but it has considerable effects on the musculoskeletal system, causing excessive fatigue, myalgia, arthralgia, muscle weakness and skeletal muscle damage. These symptoms can persist for months, decreasing the quality of life of numerous individuals. Curiously, most studies in the scientific literature focus on patients who were hospitalized due to SARS-CoV-2 infection and little is known about the mechanism of action of COVID-19 on skeletal muscles, especially of individuals who had the mild to moderate forms of the disease (non-hospitalized patients). In this review, we focus on the current knowledge about the musculoskeletal system in COVID-19, highlighting the lack of researches investigating the mild to moderate cases of infection and pointing out why it is essential to care for these patients. Also, we will comment about the need of more experimental data to assess the musculoskeletal manifestations on COVID-19-positive individuals.

Duchenne muscular dystrophy (DMD) is a muscle disease characterized by the absence of the protein dystrophin, which causes a loss of sarcolemma integrity, determining recurrent muscle injuries, decrease in muscle function, and progressive degeneration. Currently, there is a need for therapeutic treatments to improve the quality of life of DMD patients. Here, we investigated the effects of a low-intensity aerobic training (37 sessions) on satellite cells, peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α protein (PGC-1α), and different types of fibers of the psoas muscle from mdx mice (DMD experimental model). Wildtype and mdx mice were randomly divided into sedentary and trained groups (n = 24). Trained animals were subjected to 37 sessions of low-intensity running on a motorized treadmill. Subsequently, the psoas muscle was excised and analyzed by immunofluorescence for dystrophin, satellite cells, myosin heavy chain (MHC), and PGC-1α content. The minimal Feret’s diameters of the fibers were measured, and light microscopy was applied to observe general morphological features of the muscles. The training (37 sessions) improved morphological features in muscles from mdx mice and caused an increase in the number of quiescent/activated satellite cells. It also increased the content of PGC-1α in the mdx group. We concluded that low-intensity aerobic exercise (37 sessions) was able to reverse deleterious changes determined by DMD.

Duchene muscular dystrophy (DMD) is caused by the absence of the protein dystrophin, which leads to muscle weakness, progressive degeneration, and eventually death due to respiratory failure. Low-intensity eccentric training (LIET) has been used as a rehabilitation method in skeletal muscles after disuse. Recently, LIET has also been used for rehabilitating dystrophic muscles, but its effects are still unclear. The purpose of this study was to investigate the effects of 21 days of LIET in dystrophic soleus muscle. Thirty-six male mdx mice were randomized into six groups (n = 6/each): mdx sedentary group; mdx training group-3 days; mdx training group-21 days; wild-type sedentary group; wild-type training group-3 days and wild-type training group-21 days. After the training sessions, animals were euthanized, and fragments of soleus muscles were removed for immunofluorescence and histological analyses, and measurements of active force and Ca²⁺ sensitivity of the contractile apparatus. Muscles of the mdx training group-21 days showed an improvement in morphological characteristics and an increase of active force when compared to the sedentary mdx group. The results show that LIET can improve the functionality of dystrophic soleus muscle in mice.

A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario. Thus, the aim of this study was to determine the influence of 12 weeks of PT on metabolic variables and GLUT4 and FAT CD36 expression in the skeletal muscle of animals energetically impaired by ovariectomy (OVX). The trained animals swam 30 min/day, 5 days/week, at 80% of the critical load intensity. Spontaneous physical activity was measured biweekly. After training, FAT CD36 and GLUT4 expressions were quantified by immunofluorescence in the soleus, as well as muscular glycogen and triglyceride of the soleus, gluteus maximus and gastrocnemius. OVX significantly reduced FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01), while PT significantly increased FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01). PT increased soleus glycogen, and OVX decreased muscular triglyceride of gluteus maximus. Therefore, OVX can cause energy disarray through reduction in GLUT4 and FAT CD36 and their muscle substrates and PT prevented these metabolic consequences, masking ovarian estrogen’s absence.

Obesity is increasingly recognized as a condition that directly impairs skeletal muscle structure, metabolism, and endocrine function through complex molecular and cellular mechanisms extending beyond the classical concept of sarcopenic obesity. This narrative review aimed to synthesize current evidence regarding the intracellular signaling pathways, metabolic alterations, and endocrine interactions involved in obesity-induced skeletal muscle dysfunction independent of overt sarcopenia. Relevant literature from experimental, clinical, and review studies was identified through searches of PubMed, Scopus, and Web of Science databases, focusing on obesity-associated alterations in skeletal muscle metabolism, ectopic lipid accumulation, inflammatory signaling, mitochondrial dysfunction, and adipose–muscle crosstalk. Current evidence indicates that obesity per se promotes skeletal muscle dysfunction through ectopic lipid deposition, lipotoxicity, mitochondrial impairment, and chronic low-grade inflammation mediated by dysregulated intracellular signaling pathways. Altered adipomyokine signaling, including interleukin-6 and tumor necrosis factor-α, further contributes to impaired insulin signaling, reduced metabolic flexibility, oxidative stress, and compromised muscle integrity. These molecular and cellular alterations reinforce skeletal muscle as both a target and an active regulator of obesity-associated metabolic inflammation. Collectively, these findings support the concept that obesity intrinsically disrupts skeletal muscle metabolic and endocrine homeostasis independently of sarcopenic obesity and highlight the importance of targeted strategies aimed at preserving skeletal muscle metabolic function and overall metabolic health.