Inflammation: Roles in Skeletal Muscle Atrophy

Abstract

Various diseases can cause skeletal muscle atrophy, usually accompanied by inflammation, mitochondrial dysfunction, apoptosis, decreased protein synthesis, and enhanced proteolysis. The underlying mechanism of inflammation in skeletal muscle atrophy is extremely complex and has not been fully elucidated, thus hindering the development of effective therapeutic drugs and preventive measures for skeletal muscle atrophy. In this review, we elaborate on protein degradation pathways, including the ubiquitin-proteasome system (UPS), the autophagy-lysosome pathway (ALP), the calpain and caspase pathways, the insulin growth factor 1/Akt protein synthesis pathway, myostatin, and muscle satellite cells, in the process of muscle atrophy. Under an inflammatory environment, various pro-inflammatory cytokines directly act on nuclear factor-κB, p38MAPK, and JAK/STAT pathways through the corresponding receptors, and then are involved in muscle atrophy. Inflammation can also indirectly trigger skeletal muscle atrophy by changing the metabolic state of other tissues or cells. This paper explores the changes in the hypothalamic-pituitary-adrenal axis and fat metabolism under inflammatory conditions as well as their effects on skeletal muscle. Moreover, this paper also reviews various signaling pathways related to muscle atrophy under inflammatory conditions, such as cachexia, sepsis, type 2 diabetes mellitus, obesity, chronic obstructive pulmonary disease, chronic kidney disease, and nerve injury. Finally, this paper summarizes anti-amyotrophic drugs and their therapeutic targets for inflammation in recent years. Overall, inflammation is a key factor causing skeletal muscle atrophy, and anti-inflammation might be an effective strategy for the treatment of skeletal muscle atrophy. Various inflammatory factors and their downstream pathways are considered promising targets for the treatment and prevention of skeletal muscle atrophy.

Punicalagin protects against impaired skeletal muscle function in high-fat-diet-induced obese mice by regulating TET2

“…Since obesity induces chronic inflammation in the systemic state and impairs skeletal muscle function, we examined serum inflammatory markers TNF-α and IL-6 in the mice. 30 The results showed that levels of serum TNF-α and IL-6 in the HFD group were significantly higher than those in the other three groups, and supplementation with RES or PUN reduced the levels of serum inflammatory cytokines compared with the HFD group, suggesting a protective effect on skeletal muscle function (Fig. S2C and D †).…”

An integrated study of hormone-related sarcopenia for modeling and comparative transcriptome in rats

“…The Jak/STAT pathway is required for the homeostasis of different tissues and organs, and when deregulated, it promotes the initiation and progression of pathological conditions including cancer, obesity, diabetes and other metabolic diseases ( 63 , 64 ). Under an inflammatory environment, various pro-inflammatory cytokines directly act on Jak/STAT, p38MAPK and NF-κB pathways and then participate in muscle atrophy ( 65 , 66 ).…”

Redox Signaling in Chronic Kidney Disease-Associated Cachexia

“…Inflammation and oxidative stress are crucial causes of skeletal muscle atrophy according to earlier studies [ 41 ]. High ROS levels cause oxidative stress damage and accelerate the production of inflammatory molecules, which, in turn, potentiate muscle atrophy by increasing proteolysis and decreasing muscle synthesis and regeneration [ 42 , 43 ].…”

“…Several mediators of muscle protein breakdown in CKD include the UPS, caspase-3, lysosomes, ghrelin, and myostatin. These pathways can be stimulated by CKD-related alterations including metabolic acidosis, hyperphosphatemia, inflammation, oxidative stress, and insulin resistance [ 43 , 54 , 55 , 56 ]. The mRNA expression for toll-like receptor-13 (TLR-13) was increased in tibialis anterior muscles from mice subjected to subtotal nephrectomy, possibly resulting in immune system overactivity.…”