Muscle–Organ Crosstalk: The Emerging Roles of Myokines

Severinsen, Mai Charlotte Krogh; Pedersen, Bente Klarlund

doi:10.1210/endrev/bnaa016

Cited by 490 publications

(385 citation statements)

References 231 publications

Supporting

Mentioning

360

Contrasting

Unclassified

Order By: Relevance

“…As the largest metabolic and secretory organ, crosstalk between muscle and other organs, such as liver, adipose, brain, has been discussed [ 57 , [59] , [60] , [61] ]. Exercise-released myokines have been identified to confer the benefit of metabolic improvement [ 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

et al. 2020

View full text Add to dashboard Cite

Exercise and dietary intervention are currently available strategies to treat nonalcoholic fatty liver disease (NAFLD), while the underlying mechanism remains controversial. Emerging evidence shows that lipophagy is involved in the inhibition of the lipid droplets accumulation. However, it is still unclear if exercise and dietary intervention improve NAFLD through regulating lipophagy, and how exercise of skeletal muscle can modulate lipid metabolism in liver. Moreover, NAFLD is associated with aging, and little is known about the effect of lipid accumulation on aging process. Here in vivo and in vitro models, we found that exercise and dietary intervention reduced lipid droplets formation, decreased hepatic triglyceride in the liver induced by high-fat diet. Exercise and dietary intervention enhanced the lipophagy by activating AMPK/ULK1 and inhibiting Akt/mTOR/ULK1 pathways respectively. Furthermore, exercise stimulated FGF21 production in the muscle, followed by secretion to the circulation to promote the lipophagy in the liver via an AMPK-dependent pathway. Importantly, for the first time, we demonstrated that lipid accumulation exacerbated liver aging, which was ameliorated by exercise and dietary intervention through inducing lipophagy. Our findings suggested a new mechanism of exercise and dietary intervention to improve NAFLD through promoting lipophagy. The study also provided evidence to support that muscle exercise is beneficial to other metabolic organs such as liver. The FGF21-mediated AMPK dependent lipophagy might be a potential drug target for NAFLD and aging caused by lipid metabolic dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Physical activity is able reduce the risk of developing several types of cancer [92] and reduces mortality after colon cancer diagnosis [93]. These effects may be mediated by skeletal muscle-secreted myokines [94]. In an animal model, physical exercise blunted tumor growth through epinephrine-dependent mobilization of NK cells and higher immune cell infiltration into tumors [95].…”

Section: Discussionmentioning

confidence: 99%

Myokines in treatment-naïve patients with cancer-associated cachexia

et al. 2021

View full text Add to dashboard Cite

Cancer-associated cachexia is a complex metabolic syndrome characterized by weight loss and systemic inflammation. Muscle loss and fatty infiltration into muscle are associated with poor prognosis in cancer patients. Skeletal muscle secretes myokines, factors with autocrine, paracrine and/or endocrine action, which may be modified by or play a role in cachexia. This study examined myokine content in the plasma, skeletal muscle and tumor homogenates from treatment-naïve patients with gastric or colorectal stages I-IV cancer with cachexia (CC, N ¼ 62), or not (weight stable cancer, WSC, N ¼ 32). Myostatin, interleukin (IL) 15, follistatin-like protein 1 (FSTL-1), fatty acid binding protein 3 (FABP3), irisin and brain-derived neurotrophic factor (BDNF) protein content in samples was measured with Multiplex technology; body composition and muscle lipid infiltration were evaluated in computed tomography, and quantification of triacylglycerol (TAG) in the skeletal muscle. Cachectic patients presented lower muscle FSTL-1 expression (p ¼ 0.047), higher FABP3 plasma content (p ¼ 0.0301) and higher tumor tissue expression of FABP3 (p ¼ 0.0182), IL-15 (p ¼ 0.007) and irisin (p ¼ 0.0110), compared to WSC. Neither muscle TAG content, nor muscle attenuation were different between weight stable and cachectic patients. Lumbar adipose tissue (AT) index, visceral AT index and subcutaneous AT index were lower in CC (p ¼ 0.0149, p ¼ 0.0455 and p ¼ 0.0087, respectively), who also presented lower muscularity in the cohort (69.2% of patients; p ¼ 0.0301), compared to WSC. The results indicate the myokine profile in skeletal muscle, plasma and tumor is impacted by cachexia. These findings show that myokines eventually affecting muscle wasting may not solely derive from the muscle itself (as the tumor also may

show abstract

“…More recently, proteins similar to the cytokines have been discovered to be produced by the skeletal muscle itself. The so-called myokines, produced by the myocytes and released by muscle contraction during physical exercise, have autocrine, paracrine, and endocrine functions, and help perform the regulation of the immunometabolism thanks to their ability to induce significant metabolic, energetic and hormonal changes ( Cannon, 2000 ; Pillon et al, 2013 ; Iizuka et al, 2014 ; Severinsen and Pedersen, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Crosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?

et al. 2020

View full text Add to dashboard Cite

The skeletal muscle was always seen from biomechanical and biochemical views. It is well-established that an active muscle brings many benefits for different body organs and tissues, including the immune system. Since the 1970s, many studies have shown the importance of regular exercise and physical activity in increasing the body's ability to fight opportunist infections, as well as a strategy to fight established diseases. This interaction was mainly attributed to the glutamine, a non-essential amino acid produced by the active skeletal muscle and primarily consumed by rapidly dividing cells, including lymphocytes and monocytes/macrophages, as their main source of energy. Therefore, these cells' function would be significantly improved by the presence of a bigger glutamine pool, facilitating phagocytosis, antigen-presentation, proliferative capacity, cytokine synthesis and release, among other functions. Despite its importance, glutamine is not the only molecule to connect these two tissues. The presence of cytokines is crucial for a proper immune system function. Many of them have well-established pro-inflammatory properties, while others are known for their anti-inflammatory role. Interleukin-6 (IL-6), however, has been in the center of many scientific discussions since it can act as pro-and anti-inflammatory cytokine depending on the tissue that releases it. Skeletal muscle is an essential source of IL-6 with anti-inflammatory properties, regulating the function of the immune cells after tissue injury and the healing process. Therefore, this review aims to discuss further the role of these four components (glutamine, and interleukin-6, and its interface with monocytes/macrophages, and lymphocytes) on the communication between the skeletal muscle and the immune system.

show abstract

Muscle–Organ Crosstalk: The Emerging Roles of Myokines

Cited by 490 publications

References 231 publications

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

Exercise and dietary intervention ameliorate high-fat diet-induced NAFLD and liver aging by inducing lipophagy

Myokines in treatment-naïve patients with cancer-associated cachexia

Crosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?

Contact Info

Product

Resources

About