The DOI matches its Crossref record; 240 of the 249 references it cites were found in a registry or an index; none of the 156 sources its claims cite is checked for support yet.
Muscle–Organ Crosstalk: The Emerging Roles of Myokines
Open accessAbstract
Physical activity decreases the risk of a network of diseases, and exercise may be prescribed as medicine for lifestyle-related disorders such as type 2 diabetes, dementia, cardiovascular diseases, and cancer. During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners. Recent advances show that skeletal muscle produces myokines in response to exercise, which allow for crosstalk between the muscle and other organs, including brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin, as well as communication within the muscle itself. Although only few myokines have been allocated to a specific function in humans, it has been identified that the biological roles of myokines include effects on, for example, cognition, lipid and glucose metabolism, browning of white fat, bone formation, endothelial cell function, hypertrophy, skin structure, and tumor growth. This suggests that myokines may be useful biomarkers for monitoring exercise prescription for people with, for example, cancer, diabetes, or neurodegenerative diseases.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Skeletal muscle acts as an endocrine organ, releasing myokines in response to exercise that mediate crosstalk with brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, skin, immune system, and tumors. This review updates myokine biology, emphasizing IL-6 and the potential for myokines as exercise biomarkers and therapeutic targets, while noting that specific human functions remain defined for only a small fraction of myokines.
Key findings
- Myokines are defined as cytokines and other peptides produced, expressed, and released by muscle fibers that exert autocrine, paracrine, or endocrine effects; more than 650 myokines have been identified, but biological function has been described for only 5% of known myokines.
- IL-6 is a central exercise-induced myokine: it mediates anti-inflammatory effects by increasing IL-1ra and IL-10 and inhibiting endotoxin-induced TNF, delays gastric emptying, stimulates GLP-1 and insulin secretion, contributes to hepatic glucose output during exercise, and in a 12-week randomized controlled trial in abdominally obese humans, IL-6 receptor blockade abolished exercise-induced reduction in visceral adipose tissue mass.
- Muscle–organ crosstalk includes brain effects via cathepsin B and irisin, which may cross the blood–brain barrier and stimulate BDNF; aerobic exercise training for 3 months increased hippocampal volume by 12% in healthy individuals and by 16% in patients with schizophrenia.
- Other reported roles include browning of white adipose tissue (irisin, meteorin-like, IL-6), bone regulation (decorin, IL-6, IGF-1, FGF-2 positively; myostatin negatively), skin aging via IL-15, endothelial/revascularization effects via FSTL1, and anticancer effects in mice, where running reduced tumor volume and incidence across 6 tumor models via natural killer cell mobilization and IL-6-dependent redistribution.
Methods
- Narrative review/update of recent advances in the myokine field; no systematic review protocol, meta-analysis, or primary data collection is described.
- Synthesizes preclinical and human literature across multiple organs, including cited human infusion studies, exercise trials, and a randomized controlled trial of abdominally obese humans receiving tocilizumab or placebo with aerobic exercise or no exercise for 12 weeks.
- Main analysis is qualitative synthesis of published findings; no statistical analysis or formal evidence grading is reported.
Limitations
- The paper states that biological function has been described for only 5% of known myokines; many browning findings are largely restricted to rodents and have not been consistently demonstrated in humans; the exercise-induced rise in plasma irisin in humans is controversial, partly due to unspecific commercial ELISA kits; whether cathepsin B mediates enhanced cognitive function in humans is unknown; the role of meteorin-like in humans remains to be identified; and it remains to be shown that physiological exercise-released IL-6 concentrations have browning effects.
- Evident from the text: as a narrative review, it lacks a systematic search strategy, explicit inclusion criteria, risk-of-bias assessment, and quantitative synthesis, and many mechanistic conclusions rely on animal or preclinical models.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 156 cited sources checked · 0 supported · 0 flagged
In the paper
“Exercise prior to endotoxin totally blunted the increase in circulating levels of TNF‐α that was observed during a resting situation.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
What the sources say
- Not checked yetcites [113] Starkie, 2003, Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans, FASEB J. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“It was therefore expected that an infusion of rhIL-6 prior to endotoxin administration would also blunt the TNF‐α response in humans and this was in fact what was found (113).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
What the sources say
- Not checked yetcites [113] Starkie, 2003, Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans, FASEB J. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Our finding in 2000 that skeletal muscle produced and released interleukin-6 (IL-6) into the circulation (5)”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [5] Steensberg, 2000, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, J Physiol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“research during the subsequent years, demonstrating that IL-6 has multiple metabolic effects in other parts of the body (6)”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Thus, it was obvious that 1 or several humoral factors had to be released from contracting muscles to the blood (3).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [3] Goldstein, 1961, Humoral nature of hypoglycemia in muscular activity, Am J Physiol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“It was clear that signaling pathways from exercising skeletal muscle to other organs were not solely mediated via the nervous system, since electrical stimulation of paralyzed muscles in patients with no efferent or afferent nerve impulses induced the same types of physiological changes as were found in healthy human beings (1, 2).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [1] Kjaer, 1996, Hormonal and metabolic responses to electrically induced cycling during epidural anesthesia in humans, J Appl Physiol (1985). source
- Not checked yetcites [2] Mohr, 1997, Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals, Spinal Cord. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“During the past couple of decades, it has been apparent that skeletal muscle works as an endocrine organ, which can produce and secrete hundreds of myokines that exert their effects in either autocrine, paracrine, or endocrine manners.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [5] Steensberg, 2000, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, J Physiol. source
- Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Although the myokine IL-6 is mostly recognized for its regulatory effects in lipid and glucose metabolism, IL-6 also plays important roles in myogenesis.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [49] Serrano, 2008, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy, Cell Metab. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Myokines are also involved in muscle proliferation, differentiation, and regeneration independent of exercise (39, 40).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Physical inactivity is associated with high circulating basal levels of IL-6 in humans (55).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Metabolic actions
What the sources say
- Not checked yetcites [55] Fischer, 2006, Interleukin-6 in acute exercise and training: what is the biological relevance?, Exerc Immunol Rev.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 36
- Probably not a substantial claim. 3
In the paper
“The myokine IL-6 mediates the exercise-associated anti-inflammatory effects both acutely with each bout of exercise and as a consequence of training adaptation, including reduction in abdominal adiposity.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [136] Wedell-Neergaard, 2019, Exercise-induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: a randomized controlled trial, Cell Metab. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Myokines can be useful biomarkers for monitoring the type and amount of exercise that are required for the prescription of exercise for people with, for example, cancer, diabetes, or neurodegenerative diseases”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“identified IL-6 as an exercise factor and skeletal muscle as a secretory organ with endocrine functions.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [5] Steensberg, 2000, Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6, J Physiol. source
- Not checked yetcites [6] Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol Rev. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Myokines mediate communication between muscle and other organs, including brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin, as well as within the muscle itself”
- Also stated in: § Abstract · plain
“During exercise, myokines signal within the muscle and mediate muscle–organ crosstalk to the brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin (7, 29, 30).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [7] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. source
- Not checked yetcites [29] Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat Rev Rheumatol. source
- Not checked yetcites [30] Pedersen, 2019, Physical activity and muscle-brain crosstalk, Nat Rev Endocrinol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Abstract · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Myokines exert their effects on, for example, cognition, lipid and glucose metabolism, browning of white fat, bone formation, endothelial cell function, hypertrophy, skin structure, and tumor growth”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
In the paper
“identifying more than 650 myokines (38).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [38] Khan, 2019, Myokines: discovery challenges and therapeutic impediments, J Pak Med Assoc.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“During exercise, myokines signal within the muscle and mediate muscle–organ crosstalk to the brain, adipose tissue, bone, liver, gut, pancreas, vascular bed, and skin (7, 29, 30).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Abstract
What the sources say
- Not checked yetcites [7] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. source
- Not checked yetcites [29] Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat Rev Rheumatol. source
- Not checked yetcites [30] Pedersen, 2019, Physical activity and muscle-brain crosstalk, Nat Rev Endocrinol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Myostatin is a member of the transforming growth factor β (TGF-β) superfamily and negatively regulates myogenesis in an autocrine manner (43).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [43] McPherron, 1997, Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member, Nature. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“LIF protein has been shown to be secreted from human cultured myotubes; when electrically stimulated (50) LIF stimulates satellite cell proliferation (51).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [50] Broholm, 2008, Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle, J Physiol. source
- Not checked yetcites [51] Broholm, 2010, Leukaemia inhibitory factor–an exercise-induced myokine, Exerc Immunol Rev.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Some myokines exert their effect within skeletal muscle itself and are involved in the regulation of muscle mass (14) (Fig. 1).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [14] Lee, 2019, Role of myokines in regulating skeletal muscle mass and function, Front Physiol. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“It is well documented that IL-6 increases both basal glucose uptake and glucose transporter GLUT4 translocation (58).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Metabolic actions
What the sources say
- Not checked yetcites [58] Carey, 2006, Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase, Diabetes. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Massive muscle hypertrophy is seen in myostatin knockout mice, cattle, sheep, and dogs (43-45) that demonstrate an increase in fiber cross-sectional area and in fiber number.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [43] McPherron, 1997, Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member, Nature. source
- Not checked yetcites [44] Mosher, 2007, A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs, PLoS Genet. source
- Not checked yetcites [45] Grobet, 1997, A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle, Nat Genet. source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“In contrast, the muscular expression of the IL-6 receptor (IL-6R) is elevated in trained human muscle (57), suggesting that muscular sensitivity to IL-6 is increased by training adaptation.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Metabolic actions
What the sources say
- Not checked yetcites [57] Keller, 2005, Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle, J Appl Physiol (1985). source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Musclin, LIF, IL-4, IL-6, IL-7, and IL-15 promote muscle hypertrophy. Myostatin inhibits muscle hypertrophy.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Decorin has been identified as a myokine that is regulated by exercise and acts as an antagonist to myostatin (46).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [46] Kanzleiter, 2014, The myokine decorin is regulated by contraction and involved in muscle hypertrophy, Biochem Biophys Res Commun. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Genetic loss of IL-6 impaired muscle hypertrophy in vivo, whereas myotube-produced IL-6 stimulated muscle cell proliferation in a paracrine fashion (49).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [49] Serrano, 2008, Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy, Cell Metab. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Circulating levels of decorin are increased in response to exercise in humans (46), whereas exercise training reduces the levels of myostatin within muscles and blood (47, 48).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Myogenesis
What the sources say
- Not checked yetcites [46] Kanzleiter, 2014, The myokine decorin is regulated by contraction and involved in muscle hypertrophy, Biochem Biophys Res Commun. source
- Not checked yetcites [47] Saremi, 2010, Effects of oral creatine and resistance training on serum myostatin and GASP-1, Mol Cell Endocrinol. source
- Not checked yetcites [48] Hittel, 2010, Myostatin decreases with aerobic exercise and associates with insulin resistance, Med Sci Sports Exerc. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Brain-derived neurotrophic factor (BDNF) is also expressed in human skeletal muscles, but BDNF is not released into the circulation and does not work in an endocrine way.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Muscle Crosstalk > Metabolic actions
What the sources say
- Not checked yetcites [63] Matthews, 2009, Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase, Diabetologia. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Physical activity and exercise training decrease the risk of dementia (69-71) and appear to play a role in the treatment of this disease (72).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Brain Crosstalk
What the sources say
- Not checked yetcites [69] Aarsland, 2010, Is physical activity a potential preventive factor for vascular dementia? A systematic review, Aging Ment Health. source
- Not checked yetcites [70] Williams, 2010, Preventing Alzheimer’s disease and cognitive decline, Evid Rep Technol Assess (Full Rep).
- Not checked yetcites [71] Santos-Lozano, 2016, Physical activity and Alzheimer disease: a protective association, Mayo Clin Proc. source
- Not checked yetcites [72] Pedersen, 2015, Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases, Scand J Med Sci Sports. source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies in rodents (81) and humans (82) have shown that exercise increases hippocampus volume and the blood flow to this part of the brain (81).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Brain Crosstalk
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The finding that muscle contraction is sensed by the brain suggests that peripheral factors induced by exercise may be involved in direct crosstalk between working muscle and brain function (7, 29, 30, 83) (Fig. 2).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Brain Crosstalk
What the sources say
- Not checked yetcites [7] Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat Rev Endocrinol. source
- Not checked yetcites [29] Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat Rev Rheumatol. source
- Not checked yetcites [30] Pedersen, 2019, Physical activity and muscle-brain crosstalk, Nat Rev Endocrinol. source
- Not checked yetcites [83] Leardini-Tristao, 2019, Beneficial effect of exercise on cognitive function during peripheral arterial disease: potential involvement of myokines and microglial anti-inflammatory phenotype enhancement, J Clin Med. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In particular, exercise has been shown to influence neurogenesis in the dentate gyrus (67, 68) and to increase synapse plasticity (67, 68).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Brain Crosstalk
What the sources say
- Not checked yetcites [67] Cotman, 2007, Exercise builds brain health: key roles of growth factor cascades and inflammation, Trends Neurosci. source
- Not checked yetcites [68] Mattson, 2012, Energy intake and exercise as determinants of brain health and vulnerability to injury and disease, Cell Metab. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Carbohydrate ingestion during exercise blunted the exercise-induced IL-6 response, the increase in lymphocyte number as well as the cortisol (204, 205).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > Lymphocyte and neutrophil trafficking
What the sources say
- Not checked yetcites [204] Nieman, 1997, Carbohydrate supplementation affects blood granulocyte and monocyte trafficking but not function after 2.5 h or running, Am J Clin Nutr. source
- Not checked yetcites [205] Nehlsen-Cannarella, 1997, Carbohydrate and the cytokine response to 2.5 h of running, J Appl Physiol (1985). source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Following long-duration exercise of high intensity, the concentration of lymphocytes falls below pre-exercise values whereas the neutrophil number continues to increase (202, 203).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > Lymphocyte and neutrophil trafficking
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“IL-6 stimulates cortisol production and thereby induces neutrocytosis and lymphopenia.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear? Based: unclearIt may state two separate claims as one.
In the paper
“Moreover, antioxidant supplementation totally inhibited the release of IL-6 from exercising human muscle as well as the exercise-induced increase in systemic levels of cortisol (206).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > Lymphocyte and neutrophil trafficking
What the sources say
- Not checked yetcites [206] Fischer, 2004, Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle, J Physiol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“IL-6 has anti-inflammatory effects as it inhibits TNF production and stimulates the production of IL-1ra and IL-10.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
In the paper
“The infusion of IL-6 to mimic the effects of exercise led to an increase in cortisol and, consequently, a decrease in the lymphocyte number accompanied by an increase in neutrophil number (112).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > Lymphocyte and neutrophil trafficking
What the sources say
- Not checked yetcites [112] Steensberg, 2003, IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans, Am J Physiol Endocrinol Metab. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: IL-6 infusion mimics the effects of exercise.
None of the sources cited for this claim have been checked yet.
In the paper
“FSTL1 has been shown to possess cardioprotective effects, promoting endothelial cell function and thereby revascularization in animal models of cardiac injury through a mechanism that includes nitric oxide synthase (194, 195).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Vascular Bed Crosstalk
What the sources say
- Not checked yetcites [194] Ouchi, 2008, Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism, J Biol Chem. source
- Not checked yetcites [195] Oshima, 2008, Follistatin-like 1 is an Akt-regulated cardioprotective factor that is secreted by the heart, Circulation. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The acute exercise effect on lymphocytes and neutrophils is mediated by adrenaline, but the post-exercise reduction in lymphocyte number and the continuous increase in neutrophil number are mediated by both adrenaline and cortisol.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > Lymphocyte and neutrophil trafficking
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lack of exercise provokes accumulation of more visceral fat and thereby further enhances inflammation and hence a network of chronic diseases.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is obvious, that many cancers are accompanied by systemic low-grade chronic inflammation and that such inflammation may drive tumor progression.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Cancer Crosstalk
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
In the paper
“Using a mouse model with conditional expression of the Il6 gene, it was found that IL6 derived from adipocytes increased, while IL6 derived from myeloid cells and muscle suppressed, macrophage infiltration of adipose tissue.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
What the sources say
- Not checked yetcites [215] Han, 2020, Regulation of adipose tissue inflammation by interleukin 6, Proc Natl Acad Sci U S A. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In humans, exercise training can induce anti-inflammatory effects both acutely with each bout of exercise and via long-term training adaptation including reduction in abdominal adiposity.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Accumulation of visceral fat, which is more inflamed than subcutaneous fat, leads to chronic systemic inflammation that predisposes to atherosclerosis, elevated blood lipids, insulin resistance, neurodegeneration, muscle waste, and anemia, factors that are likely to lead to decreased physical activity.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Exercise training will lead to a decrease in visceral and cardiac fat mass (136, 138, 221) and hence a decrease in circulating inflammatory molecules via a mechanism that involves exercise-induced increase in IL-6 (136), as described above.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Muscle–Immune Inflammation Crosstalk > The anti-inflammatory effects of exercise
What the sources say
- Not checked yetcites [136] Wedell-Neergaard, 2019, Exercise-induced changes in visceral adipose tissue mass are regulated by IL-6 signaling: a randomized controlled trial, Cell Metab. source
- Not checked yetcites [138] Christensen, 2019, Aerobic exercise induces cardiac fat loss and alters cardiac muscle mass through an interleukin-6 receptor-dependent mechanism: cardiac analysis of a double-blind randomized controlled clinical trial in abdominally obese humans, Circulation. source
- Not checked yetcites [221] Christensen, 2019, Effect of aerobic and resistance exercise on cardiac adipose tissues: secondary analyses from a randomized clinical trial, JAMA Cardiol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lack of physical activity is associated with a large network of diseases, including type 2 diabetes, cardiovascular diseases, cancer, dementia, and osteoporosis (72, 121)”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Myokines and Other “Kines”: Adipokines, Hepatokines, and Batokines
What the sources say
- Not checked yetcites [72] Pedersen, 2015, Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases, Scand J Med Sci Sports. source
- Not checked yetcites [121] Pedersen, 2019, The physiology of optimizing health with a focus on exercise as medicine, Annu Rev Physiol. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These hepatokines increase in the circulation after muscle work and appear to be involved in mediating some of the metabolic effects of exercise.”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Myokines and Other “Kines”: Adipokines, Hepatokines, and Batokines
What the sources say
- Not checked yetcites [232] Weigert, 2019, Hepatokines-a novel group of exercise factors, Pflugers Arch. source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Hepatokines include FGF-21, follistatin, angiopoietin-like protein 4, heat shock protein 72, and IGF binding protein, which are all released from the liver during or immediately after an exercise bout (232).”
§ Muscle–Organ Crosstalk: The Emerging Roles of Myokines > Myokines and Other “Kines”: Adipokines, Hepatokines, and Batokines
What the sources say
- Not checked yetcites [232] Weigert, 2019, Hepatokines-a novel group of exercise factors, Pflugers Arch. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Recombinant human IL-6 infused to mimic exercise-induced plasma IL-6 levels has the same physiological effects as endogenous muscle-derived IL-6 during exercise.
“Healthy young males underwent 2 hours of bicycle exercise on 3 separate occasions at (1) a relatively high intensity; (2) a low intensity, and (3) a low intensity + infusion of IL-6 to mimic the plasma levels of IL-6 observed during high-intensity exercise.”
The paper relies on this without support.
IL-6 receptor blockade with tocilizumab specifically isolates IL-6's role in exercise-induced visceral fat loss.
“Abdominally obese humans were randomized to tocilizumab (IL-6 receptor antibody) or placebo during an intervention of 12 weeks with either aerobic exercise or no exercise (136, 137).”
“However, this effect was abolished by IL-6 receptor blockade (136).”
The paper relies on this without support.
IL-6 infusion mimics the effects of exercise.
“The infusion of IL-6 to mimic the effects of exercise led to an increase in cortisol and, consequently, a decrease in the lymphocyte number accompanied by an increase in neutrophil number (112).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Skeletal muscle also functions as an endocrine organ.”
From Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity (2025) · cites this paper as [109]
The cited source says what the claim attributes to it.
In the citing paper
“Though human research on this topic is limited, preclinical studies suggest that loss of muscle mass or function can detrimentally affect numerous physiological systems.”
From Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity (2025) · cites this paper as [109]
The cited source says what the claim attributes to it.
In the citing paper
“Muscle contraction during exercise triggers the release of numerous autocrine, paracrine, and endocrine mediators collectively known as myokines.”
From Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity (2025) · cites this paper as [109]
The cited source says what the claim attributes to it.
In the citing paper
“skeletal muscle also functions as an autocrine, endocrine, and paracrine tissue, especially during physical exercise, via the secretion of myokines [35].”
From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [35]
In the citing paper
“Dysregulation in myokine secretion can arise in the pathogenesis of age-related conditions, such as sarcopenia [104,105].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [105]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
GLP-1-producing pancreatic cells differ between the text and its cited reference
MinorThe gut section attributes IL-6-stimulated GLP-1 secretion to pancreatic β-cells, whereas the title of the cited reference attributes it to alpha cells.
“A classic study by Ellingsgaard et al. (108) elegantly showed that acute elevations in IL-6 stimulates GLP-1 secretion from both intestinal L‐cells and pancreatic β‐cells, leading to improved secretion of insulin.”
“108. Ellingsgaard H, Hauselmann I, Schuler B, et al. Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med. 2011; 17(11): 1481- 1489. 22037645 PMC4286294”
IL-6 is said to both stimulate and inhibit appetite
MinorThe figure says IL-6 stimulates appetite, while the appetite section says it suppresses feeding and may inhibit appetite.
“Figure: Figure 2. Cathepsin B and irisin cross the blood–brain barrier and stimulate BDNF production, which leads to hippocampal neurogenesis. IL-6 stimulates appetite.”
“Thus, it is likely that muscle-derived IL-6, elicited by exercise of long duration and high intensity, may inhibit appetite.”
Myostatin is assigned opposite effects on bone resorption
MinorThe same paragraph says myostatin reduces osteoclast formation and bone destruction, then calls it a positive regulator of bone resorption.
“myostatin reduces osteoclast formation and bone destruction in a TNF-α transgenic mouse model of rheumatoid arthritis (162).”
“Thus, whereas myostatin is a negative regulator of bone, it is a positive regulator of bone resorption.”
Citations
Cites
Positional cloning of the mouse obese gene and its human homologue
Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L., & Friedman, J. M. (1994) · Nature · doi:10.1038/372425a0 · Cited by 13,419
Exercise training increases size of hippocampus and improves memory
Erickson, K. I., Voss, M. W., Prakash, R. S., Basak, C., Szabo, A., Chaddock, L., Kim, J. S., Heo, S., Alves, H., White, S. M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015950108 · Cited by 4,855 · cited 1×
“Studies in rodents (81) and humans (82) have shown that exercise increases hippocampus volume and the blood flow to this part of the brain (81).”
BackgroundA PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810
Regulation of skeletal muscle mass in mice by a new TGF-p superfamily member
McPherron, A. C., Lawler, A. M., & Lee, S.-J. (1997) · Nature · doi:10.1038/387083a0 · Cited by 4,013
Type 2 diabetes as an inflammatory disease
Donath, M. Y., & Shoelson, S. E. (2011) · Nature Reviews Immunology · doi:10.1038/nri2925 · Cited by 3,737 · cited 1×
“Whereas TNF-α may inhibit β‐cell function indirectly, IL‐1β has been identified as a direct key player in β‐cell damage (183-189), although IL-1β inhibition with canakinumab did not reduce the incidence of diabetes (190).”
BackgroundExercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases
Pedersen, B. K., & Saltin, B. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12581 · Cited by 3,514 · cited 2×
“Physical activity and exercise training decrease the risk of dementia (69-71) and appear to play a role in the treatment of this disease (72).”
BackgroundSelf-citationThe anti-inflammatory effect of exercise
Petersen, A. M. W., & Pedersen, B. K. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00164.2004 · Cited by 3,100 · cited 1×
“The anti-inflammatory effects of exercise Physical inactivity is associated with low-grade chronic inflammation, not least when a physical inactive lifestyle is associated with obesity (29, 142, 144, 145, 207-210).”
BackgroundSelf-citationMuscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · cited 6×
“The role of myokines has previously been reviewed (7, 11-37), identifying more than 650 myokines (38).”
BackgroundInfluentialSelf-citationKahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799 · cited 1×
“Several other studies have described that IL-6 can increase intramyocellular (58-60) or whole body (61) fatty acid oxidation via AMPK activation (58, 62).”
BackgroundExercise: a behavioral intervention to enhance brain health and plasticity
Cotman, C. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(02)02143-4 · Cited by 2,739 · cited 1×
“Other studies have shown that an active lifestyle is associated with learning and memory (74), executive functions (75), language and reaction time (76), academic achievement in children, and intelligence in adolescents (77).”
Background
Flagged first, then by citations
9 of the 249 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The aetiology and molecular landscape of insulin resistance
James, D. E., Stöckli, J., & Birnbaum, M. J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00390-6 · Cited by 736
The crucial role and mechanism of insulin resistance in metabolic disease
Zhao, X., An, X., Yang, C., Sun, W., Ji, H., & Lian, F. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1149239 · Cited by 675
Hand grip strength as a proposed new vital sign of health: a narrative review of evidences
Vaishya, R., Misra, A., Vaish, A., Ursino, N., & D’Ambrosi, R. (2024) · Journal of Health, Population and Nutrition · doi:10.1186/s41043-024-00500-y · Cited by 385
El Assar, M., Álvarez-Bustos, A., Sosa, P., Angulo, J., & Rodríguez-Mañas, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158713 · Cited by 371
“Massive muscle hypertrophy is observed in myostatin knockout mice, which show an increase in fiber CSA and fiber number [96].”
BackgroundInfluentialGao, Y., Zhang, W., Zeng, L.-Q., Bai, H., Li, J., Zhou, J., Zhou, G., Fang, C., Wang, F., & Qin, X.-J. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101635 · Cited by 298
Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease
Church, F. (2021) · Biomolecules · doi:10.3390/biom11040612 · Cited by 325
The role of hepatokines in NAFLD
Stefan, N., Schick, F., Birkenfeld, A. L., Häring, H., & White, M. F. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.01.006 · Cited by 288
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278
Bilski, J., Pierzchalski, P., Szczepanik, M., Bonior, J., & Zoladz, J. A. (2022) · Cells · doi:10.3390/cells11010160 · Cited by 271
“Disorders in myokine secretion may play a role in the pathogenesis of age-related and metabolic diseases, including obesity, T2D, sarcopenia, and SO [111,243,244].”
BackgroundNash, D., Hughes, M. G., Butcher, L., Aicheler, R., Smith, P., Cullen, T., & Webb, R. (2023) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.14241 · Cited by 182
Muscle matters: The effects of medically induced weight loss on skeletal muscle
Prado, C. M., Phillips, S. M., Gonzalez, M. C., & Heymsfield, S. B. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00272-9 · Cited by 177
Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis
Arosio, B., Calvani, R., Ferri, E., Coelho-Junior, H. J., Carandina, A., Campanelli, F., Ghiglieri, V., Marzetti, E., & Picca, A. (2023) · Nutrients · doi:10.3390/nu15081853 · Cited by 165
“These proteins are secreted into the circulation by myotubes and can hold both pro- and anti-inflammatory signaling roles, such as IL-6, IL-7, IL-8, IL-15, BDNF, angiopoietin-like 4, myostatin, irisin, and gamma-amino isobutyric acid [114].”
BackgroundGut microbiota–bile acid–skeletal muscle axis
Mancin, L., Wu, G. D., & Paoli, A. (2022) · Trends in Microbiology · doi:10.1016/j.tim.2022.10.003 · Cited by 183
Food Polyphenols and Type II Diabetes Mellitus: Pharmacology and Mechanisms
Naz, R., Saqib, F., Awadallah, S. M., Wahid, M., Latif, M. F., Iqbal, I., & Mubarak, M. S. (2023) · Molecules · doi:10.3390/molecules28103996 · Cited by 178
“By producing myokines, skeletal muscles contribute significantly to the endocrine response and T2D [63].”
BackgroundCircadian rhythms and cancers: the intrinsic links and therapeutic potentials
Zhou, L., Zhang, Z., Nice, E. C., Huang, C., Zhang, W., & Tang, Y. C. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01238-y · Cited by 163
The exercise IL-6 enigma in cancer
Orange, S. T., Leslie, J., Ross, M., Mann, D. A., & Wackerhage, H. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.08.001 · Cited by 158
“Many of the bioactive molecules regulated by acute exercise have capacity to impact biological processes related to cell cycle progression and proliferation [106].”
Schumann, M., Feuerbacher, J. F., Sünkeler, M., Freitag, N., Rønnestad, B. R., Doma, K., & Lundberg, T. R. (2022) · Sports Medicine · doi:10.1007/s40279-021-01587-7 · Cited by 156
Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk
Scisciola, L., Fontanella, R. A., Surina, S., Cataldo, V., Paolisso, G., & Barbieri, M. (2021) · Life · doi:10.3390/life11020173 · Cited by 153
“Myokines are muscle-produced factors that improve brain function as cognition, memory, and motor coordination [36].”
BackgroundExercise mimetics: harnessing the therapeutic effects of physical activity
Gubert, C., & Hannan, A. J. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00217-1 · Cited by 157
Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity
Mechanick, J. I., Butsch, W. S., Christensen, S. M., Hamdy, O., Li, Z., Prado, C. M., & Heymsfield, S. B. (2025) · Obesity Reviews · doi:10.1111/obr.13841 · Cited by 149
Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders
Kitamura, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043219 · Cited by 146
“Given that skeletal muscle plays a pivotal role in energy metabolism, physical activity, and myokine production [96,169], defects in this muscle group, such as sarcopenia, severely worsen the complications of metabolic disorders [170].”
BackgroundMyokines and Resistance Training: A Narrative Review
Zunner, B. E. M., Wachsmuth, N. B., Eckstein, M. L., Scherl, L., Schierbauer, J., Haupt, S., Stumpf, C., Reusch, L., & Moser, O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073501 · Cited by 146
“most common non-communicable diseases [5,10,11].”
Stefanakis, K., Kokkorakis, M., & Mantzoros, C. S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156057 · Cited by 142
BDNF Impact on Biological Markers of Depression—Role of Physical Exercise and Training
Murawska‐Ciałowicz, E., Wiatr, M., Ciałowicz, M., de Assis, G. G., Borowicz, W., Rocha‐Rodrigues, S., Paprocka‐Borowicz, M., & Marques, A. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18147553 · Cited by 149
“They likely act in an endocrine-dependent manner to favor the communication between skeletal muscle and distant organs, creating a network that integrates several signals coming from various organs [77,84,97,101].”
BackgroundInfluentialMa, S., Xing, X., Huang, H., Gao, X., Xu, X., Yang, J., Liao, C., Zhang, X., Liu, J., Tian, W., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.10.013 · Cited by 145
Kopczyńska, J., & Kowalczyk, M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1380476 · Cited by 160
Espino-González, E., Dalbram, E., Mounier, R., Gondin, J., Farup, J., Jessen, N., & Treebak, J. T. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.02.014 · Cited by 141
Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies
Wang, K., Liu, Q., Tang, M., Qi, G., Qiu, C., Huang, Y. H., Yu, W., Wang, W., Sun, H., Ni, X., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115407 · Cited by 145
Mechanisms by Which Skeletal Muscle Myokines Ameliorate Insulin Resistance
Balakrishnan, R., & Thurmond, D. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094636 · Cited by 143
Bone and Muscle Crosstalk in Aging
He, C., He, W., Hou, J., Chen, K., Huang, M., Yang, M., Luo, X., & Li, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.585644 · Cited by 129
The Role of GDF15 as a Myomitokine
Johann, K., Kleinert, M., & Klaus, S. (2021) · Cells · doi:10.3390/cells10112990 · Cited by 125
“This includes many mitokines, which are triggered in response to mitochondrial stress imposed during contractions and that contribute to the multitude of metabolic and physiological changes associated with exercise [61].”
BackgroundHulett, N. A., Scalzo, R. L., & Reusch, J. E. B. (2022) · Nutrients · doi:10.3390/nu14030647 · Cited by 140
Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk
Sanches, J. M., Zhao, L. N., Salehi, A. A., Wollheim, C. B., & Kaldis, P. (2021) · FEBS Journal · doi:10.1111/febs.16306 · Cited by 136
Lü, Y., Bu, F., Wang, F., Liu, L., Zhang, S., Wang, G., & Hu, X. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00341-5 · Cited by 128
“Moreover, exercise can induce skeletal muscle production of myokines into the blood [31], some of which promote expression of BDNF in hippocampus and inhibit production of inflammatory factors [32].”
BackgroundOudbier, S. J., Goh, J., Looijaard, S. M. L. M., Reijnierse, E. M., Meskers, C. G. M., & Maier, A. B. (2022) · The Journals of Gerontology Series A · doi:10.1093/gerona/glac121 · Cited by 125
“The quantity of myokines may be reduced due to low levels of physical activity that could contribute to the loss of motor units that accompanies aging, thereby influencing the aforementioned pathways of interest (inflammation, insulin metabolism, and mitochondria) in the brain microenvironment, via alterations to thei…”
BackgroundMuscle-to-tumor crosstalk: The effect of exercise-induced myokine on cancer progression
Huang, Q., Wu, M., Wu, X., Zhang, Y., & Xia, Y. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188761 · Cited by 124
Muscle-Organ Crosstalk: Focus on Immunometabolism
Bay, M. L., & Pedersen, B. K. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.567881 · Cited by 117
Self-citationBiological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging
Mancinelli, R., Checcaglini, F., Coscia, F., Gigliotti, P. V., Fulle, S., & Fanò, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168520 · Cited by 113
“However, irisin also appears to have a positive effect on cognitive function and to play a role in bone metabolism regulation [2,123].”
BackgroundDaily, J. W., & Park, S. (2022) · Cells · doi:10.3390/cells11030338 · Cited by 115
“Follistatin, IGF-1, decorin, irisin, and osteoglycin are involved in bone formation, whereas IL-15 regulates bone resorption [31].”
BackgroundNay, K., Smiles, W. J., Kaiser, J., McAloon, L. M., Loh, K., Galić, S., Oakhill, J. S., Gundlach, A. L., & Scott, J. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084052 · Cited by 112
“Recent advances demonstrate that skeletal muscle produces myokines and metabolites in response to exercise, which permit crosstalk between the muscle and distal organs [66].”
BackgroundCrosstalk Between Skeletal Muscle and Immune System: Which Roles Do IL-6 and Glutamine Play?
Rogeri, P. S., Gasparini, S. O., Martins, G. L., Costa, L. K. F., Araujo, C. C., Lugaresi, R., Kopfler, M., & Lancha, A. H. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.582258 · Cited by 108
“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…”
BackgroundSarcopenia and Diabetes: A Detrimental Liaison of Advancing Age
Lisco, G., Disoteo, O., Tullio, A. D., Geronimo, V. D., Giagulli, V. A., Monzani, F., Jirillo, E., Cozzi, R. C., Guastamacchia, E., Pergola, G. D., et al. (2023) · Nutrients · doi:10.3390/nu16010063 · Cited by 111
“Preserving skeletal muscle endocrine functions means maintaining essential crosstalk between skeletal muscle and several tissues, such as the brain, adipose tissue, bones, the liver, gut microbiome, pancreatic islets, microvasculature, skin, and muscle itself [226].”
BackgroundPlaza‐Díaz, J., Izquierdo, D., Torres‐Martos, Á., Baig, A. T., Aguilera, C. M., & Ruiz‐Ojeda, F. J. (2022) · Biomedicines · doi:10.3390/biomedicines10010126 · Cited by 121
You, Y., Chen, Y., Wei, M., Tang, M., Lu, Y., Zhang, Q., & Cao, Q. (2024) · Nutrients · doi:10.3390/nu16060777 · Cited by 99
“Mechanistically, RPA stimulates the release of myokines, which are cytokines secreted by muscles during exercise, exerting systemic anti-inflammatory effects [35,36].”
BackgroundHow does the skeletal muscle communicate with the brain in health and disease?
Isaac, A. R., Lima‐Filho, R. A. S., & Lourenco, M. V. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108744 · Cited by 99
Organ crosstalk and dysfunction in sepsis
Borges, A., & Bento, L. F. N. (2024) · Annals of Intensive Care · doi:10.1186/s13613-024-01377-0 · Cited by 107
“Both bone and muscle regulate the utilization, distribution, and delivery of nutrients and other substrates [106].”
BackgroundSkeletal interoception in bone homeostasis and pain
Lv, X., Gao, F., & Cao, X. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.025 · Cited by 94
Pal, S. C., & Méndez‐Sánchez, N. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i25.3999 · Cited by 98
Exercise of high intensity ameliorates hepatic inflammation and the progression of NASH
Fredrickson, G., Barrow, F., DIETSCHE, K. B., Parthiban, P., Khan, S. M., Robert, S., Demirchian, M., Rhoades, H., Wang, H., Adeyi, O. A., et al. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101270 · Cited by 91
Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases
Feng, L., Chen, Z., & Bian, H. (2024) · MedComm · doi:10.1002/mco2.649 · Cited by 100
“121 By and large, the exploration of myokines function has gradually revealed the effect of exercise on various functions of the body and promoted the understanding of relevant diseases.”
BackgroundBeyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology
Torre, S. D. (2021) · Cells · doi:10.3390/cells10092502 · Cited by 91
Effects of Overweight/Obesity on Motor Performance in Children: A Systematic Review
Barros, W. M. A., da Silva, K. G., Silva, R. K. P., Souza, A. P. D. S., da Silva, A. B. J., Silva, M. R. M., Fernandes, M. S. D. S., de Souza, S. L., & Souza, V. D. O. N. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.759165 · Cited by 87
Hu, X., Wang, Z., Wang, W., Cui, P., Kong, C., Chen, X., & Lu, S. (2023) · Journal of Advanced Research · doi:10.1016/j.jare.2023.09.001 · Cited by 94
The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations
Leuchtmann, A. B., Adak, V., Dilbaz, S., & Handschin, C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.709807 · Cited by 84
“The long-term effects of training, in addition, may be positively influenced by the above-described reduction in visceral adipose tissue, a main contributor to the chronic systemic low-grade inflammatory state observed in the context of obesity (Severinsen and Pedersen, 2020).”
BackgroundInfluentialReyes-Furrer, A. A., Andrade, S. D., Bachmann, D., Jeker, H., Steinmann, M., Accart, N., Dunbar, A., Rausch, M., Bono, E., Rimann, M., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02691-0 · Cited by 80
Jo, D., Yoon, G., Kim, O. Y., & Song, J. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112636 · Cited by 86
Bettariga, F., Taaffe, D. R., Galvão, D. A., Lopez, P., Bishop, C., Markarian, A. M., Natalucci, V., Kim, J.-S., & Newton, R. U. (2024) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2024.04.005 · Cited by 83
Hird, E. J., Slanina-Davies, A., Lewis, G., Hamer, M., & Roiser, J. P. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02922-y · Cited by 79
Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining
Liu, Y., Zhou, R., Guo, Y., Hu, B., Xie, L., An, Y., Wen, J., Liu, Z., Zhou, M., Kuang, W., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2024.12.005 · Cited by 78
Sarcopenia, frailty and type 2 diabetes mellitus (Review)
Nishikawa, H., Fukunishi, S., Asai, A., Yokohama, K., Ohama, H., Nishiguchi, S., & Higuchi, K. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12494 · Cited by 80
Exercise and immunometabolic regulation in cancer
Koelwyn, G. J., Zhuang, X., Tammela, T., Schietinger, A., & Jones, L. W. (2020) · Nature Metabolism · doi:10.1038/s42255-020-00277-4 · Cited by 84
López, P., Newton, R. U., Taaffe, D. R., Singh, F., Buffart, L. M., Spry, N. A., Tang, C., Fred Saad, C., & Galvao, D. A. (2021) · Prostate Cancer and Prostatic Diseases · doi:10.1038/s41391-021-00442-0 · Cited by 77
The wonder exerkines—novel insights: a critical state-of-the-art review
Magliulo, L., Bondi, D., Pini, N., Marramiero, L., & Filippo, E. S. D. (2021) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-021-04264-5 · Cited by 77
Molecular control of endurance training adaptation in male mouse skeletal muscle
Furrer, R., Heim, B., Schmid, S., Dilbaz, S., Adak, V., Nordström, K. J. V., Ritz, D., Steurer, S. A., Walter, J., & Handschin, C. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00891-y · Cited by 73
“The plasticity evoked by exercise training leads to a pleiotropic remodelling of the function of many organs beyond muscle, with potent health benefits 1,6,7,32,33 .”
BackgroundGao, K., Ma, W., Huck, S., Li, B.-L., Zhang, L., Zhu, J., Li, T. X., & Zhou, D. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.755705 · Cited by 68
Mittenbühler, M. J., Jedrychowski, M. P., Vranken, J. G. V., Sprenger, H., Wilensky, S. E., Dumesic, P. A., Sun, Y., Tartaglia, A., Laznik-Bogoslavski, D., Mu, A., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.12.014 · Cited by 68
Cytokines as key players in obesity low grade inflammation and related complications
Uti, D. E., Atangwho, I. J., Omang, W. A., Alum, E. U., Obeten, U. N., Udeozor, P. A., Agada, S. A., Bawa, I., & Ogbu, C. O. (2025) · Obesity Medicine · doi:10.1016/j.obmed.2025.100585 · Cited by 116
Bone and muscle crosstalk in ageing and disease
Kirk, B., Lombardi, G., & Duque, G. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01088-x · Cited by 89
“The ability of osteokines and myokines to module other tissues 191,192 might explain why low bone density or low muscle mass predicts disease-specific and all-cause mortality 193,194 .”
The Emerging Role of Irisin in Cardiovascular Diseases
Fu, J., Li, F., Tang, Y., Cai, L., Zeng, C., Yang, Y., & Yang, J. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.022453 · Cited by 78
Crosstalk Between the Neuroendocrine System and Bone Homeostasis
Zhao, Y., Peng, X., Wang, Q., Zhang, Z., Wang, L., Xu, Y., Yang, H., Bai, J., & Geng, D. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad025 · Cited by 75
Sheng, R., Cao, M., Song, M., Wang, M., Zhang, Y., Shi, L., Xie, T., Li, Y., Wang, J., & Rui, Y. (2023) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2023.09.007 · Cited by 85
“…of myokines to positively (e.g., irisin, IGF-1, FGF2, decorin, and IL-6) or negatively (e.g., myostatin and FGF21) regulate bone metabolism, and bone can produce osteokines (e.g., OCN, RANKL, and SOST) to in fl uence muscle metabolism inversely, as previously reviewed [5,14,17,25 – 27] (Fig.”
ResultFunctional role of skeletal muscle-derived interleukin-6 and its effects on lipid metabolism
Lin, W., Song, H., Shen, J., Wang, J., Yang, Y., Yang, Y., Cao, J., Xue, L., Zhao, F., Xiao, T., et al. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1110926 · Cited by 74
“Interleukin 6 (IL-6) refers to a potent myokine (Huh, 2018; Severinsen and Pedersen, 2020).”
BackgroundLoss of neuromuscular junction integrity and muscle atrophy in skeletal muscle disuse
Sirago, G., Pellegrino, M. A., Bottinelli, R., Franchi, M. V., & Narici, M. V. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101810 · Cited by 66
Gu, X., Wang, L., Liu, S., & Shan, T. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155379 · Cited by 74
Iglesias, P. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134490 · Cited by 79
“Catecholamines stimulate the production and release of myokines in skeletal muscle, facilitating their autocrine, paracrine and endocrine action, and contributing to the systemic effects of exercise on metabolism and homeostasis [7].”
Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
Fang, P., She, Y., Yu, M., Min, W., Shang, W., & Zhang, Z. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101829 · Cited by 62
Glucagon-like peptide-1 receptor agonists and muscle mass effects
Ceasovschih, A., Asaftei, A., Lupo, M. G., Kotlyarov, S., Bartušková, H., Balta, A., Sorodoc, V., Sorodoc, L., & Banach, M. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107927 · Cited by 64
Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise
de Souza, P. B., Borba, L. A., de Jesus, L. C., Valverde, A. P., Gil‐Mohapel, J., & Rodrigues, A. L. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242316870 · Cited by 68
“Moreover, IL-6 can promote an increase in anti-inflammatory cytokines, such as IL-1 receptor antagonist (IL-1ra; which in turn inhibits IL-1 β signal transduction) and IL-10 (which inhibits synthesis of TNF-α ) [179].”
BackgroundHepatokines—A novel group of exercise factors
Weigert, C., Hoene, M., & Plomgaard, P. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2216-y · Cited by 57
Ayari, S., Abellard, A., Carayol, M., Guedj, É., & Gavarry, O. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112141 · Cited by 65
Kang, X., Qian, J., Shi, Y.-X., Bian, X., Zhang, L., Li, G., Wang, L., Zhao, J., Dong, Z., Yang, M., et al. (2024) · Cell stem cell · doi:10.1016/j.stem.2023.12.011 · Cited by 59
Lifestyle factors as determinants of atherosclerotic cardiovascular health
Schmidt‐Trucksäss, A., Lichtenstein, A. H., & von Känel, R. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117577 · Cited by 74
The Impact of Exercise on Immunity, Metabolism, and Atherosclerosis
Meyer-Lindemann, U., Moggio, A., Dutsch, A., Kessler, T., & Sager, H. B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043394 · Cited by 62
“VO2, the maximal oxygen uptake during physical exertion, positively correlates with the extent of naïve T lymphocytes [68] and the number of Interleukin-10 (IL-10)-producing TREG cells [39,47].”
BackgroundInfluentialLiver and muscle circadian clocks cooperate to support glucose tolerance in mice
Smith, J. G., Koronowski, K. B., Mortimer, T., Sato, T., Greco, C. M., Petrus, P., Verlande, A., Chen, S., Samad, M., Deyneka, E., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112588 · Cited by 58
Liu, Y., Tan, D., Wang, P., Xiao, T., Wang, X., & Zhang, T. (2024) · Scientific Reports · doi:10.1038/s41598-024-71797-2 · Cited by 60
“…studies have found that the self-control levels of the exercise intervention group are higher than those of the control group 64,65 , possibly due to the promotion of metabolic and developmental levels in brain regions associated with self-control as a result of physical activity 66–68 .”
BackgroundIrisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities
Trettel, C. D. S., Pelozin, B. R. D. A., Barros, M. P., Bachi, A. L. L., Braga, P. G. S., Momesso, C. M., Furtado, G. E., Valente, P. A., de Oliveira, E. M., Hogervorst, E., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1106529 · Cited by 56
Myokines: Metabolic regulation in obesity and type 2 diabetes
Chen, Z.-T., Weng, Z.-X., Lin, J. D., & Meng, Z.-X. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae006 · Cited by 58
“…and stress, skeletal muscle secretes myokines, which are then found to participate in physiological processes, including the metabolism of lipids and glucose, and the browning of white adipose tissue (WAT), indicating that they are important in the development of obesity and diabetes [6, 31].”
Kong, J., Xie, Y., Fan, R., Wang, Q., Luo, Y., & Dong, P. (2025) · European journal of medical research · doi:10.1186/s40001-025-02751-9 · Cited by 74
“These organs communicate through metabolic, neural, and immune pathways, with exercise playing a key role in optimizing their interactions [48, 49].”
Eimonte, M., Paulauskas, H., Daniusevičiūtė, L., Eimantas, N., Vitkauskienė, A., Dauksaite, G., Solianik, R., & Brazaitis, M. (2021) · International Journal of Hyperthermia · doi:10.1080/02656736.2021.1915504 · Cited by 64
“Moreover, IL-6 plays important roles as a myokine in metabolism, browning of white fat, bone formation, hypertrophy, and tumor growth [67].”
BackgroundJimeno‐Almazán, A., Martínez-Cava, A., Buendía‐Romero, Á., Franco‐López, F., Sánchez‐Agar, J. A., Martínez, B. J. S.-Á., Tufano, J. J., Pallarés, J. G., & Courel‐Ibáñez, J. (2022) · Internal and Emergency Medicine · doi:10.1007/s11739-022-03039-0 · Cited by 56
Frühbeck, G., Catalán, V., Valentí, V., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00762-0 · Cited by 53
“To date, the potential beneficial effects of FNDC4 and FNDC5 on COVID-19 outcomes include anti-obesity [5–7] and anti-inflammatory [4, 5] activities, such as inhibiting macrophage M1 polarization and proinflammatory cytokine production in AT.”
BackgroundRamsey, K. A., Meskers, C. G. M., & Maier, A. B. (2021) · The Lancet Healthy Longevity · doi:10.1016/s2666-7568(21)00203-8 · Cited by 59
The role of myokines in cancer: crosstalk between skeletal muscle and tumor
Park, S.-Y., Hwang, B.-O., & Song, N. (2023) · BMB Reports · doi:10.5483/bmbrep.2023-0064 · Cited by 52
Ringleb, M., Javelle, F., Haunhorst, S., Bloch, W., Fennen, L., Baumgart, S., Drube, S., Reuken, P. A., Pletz, M. W., Wagner, H., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202301619r · Cited by 73
“9 Furthermore, it is well established that myokines greatly impact the regulation of immunological processes in response to physical activity.”
BackgroundMurawska‐Ciałowicz, E., de Assis, G. G., Clemente, F. M., Feito, Y., Šťastný, P., Zuwała−Jagiełło, J., Bibrowicz, B., & Wolański, P. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-88069-y · Cited by 59
Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health
Barnes, J. N., Pearson, A. G., Corkery, A. T., Eisenmann, N. A., & Miller, K. B. (2021) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617721000394 · Cited by 54
“…synthesized and released by contracting skeletal muscle such as cathepsin B and irisin, may integrate with other growth factors or work via separate pathways to preserve brain vasculature and neural tissue, though these mechanisms are only beginning to be explored (Severinsen & Pedersen, 2020).”
BackgroundSkeletal muscle atrophy, regeneration, and dysfunction in heart failure: Impact of exercise training
Gallagher, H., Hendrickse, P. W., Pereira, M. G., & Bowen, T. S. (2023) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2023.04.001 · Cited by 56
Myokine-mediated muscle-organ interactions: Molecular mechanisms and clinical significance
Yi, J., Chen, J., Yao, X., Zhao, Z., Niu, X., Li, X., Sun, J., Ji, Y., Shang, T., Gong, L., et al. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.117326 · Cited by 68
Lemes, V., Gaya, A. R., Sadarangani, K. P., Aguilar-Farias, N., Rodriguez-Rodriguez, F., Martins, C. M. D. L., Fochesatto, C., & Cristi-Montero, C. (2021) · Frontiers in Pediatrics · doi:10.3389/fped.2021.656916 · Cited by 48
Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders
Cento, A. S., Leigheb, M., Caretti, G., & Penna, F. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00739-6 · Cited by 49
Metadata
- Authors
- Severinsen, M. C. K., & Pedersen, B. K.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Pedersen, Bente Klarlund
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2020-05-11
- Volume
- 41
- Issue
- 4
- Pages
- 594-609
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC7288608
- OpenAlex
- W3024249113
- Semantic Scholar
- e9cdafc34025c5fb05281385f410991c40c566f0
- Cited by
- 1,226
- References
- 249
- Citations by year
- 2026: 280 · 2025: 274 · 2024: 235 · 2023: 191 · 2022: 138 · 2021: 92 · 2020: 15
- FWCI
- 13.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Endocrine Reviews (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Funders
- TrygFonden
- Topics
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- myokines, skeletal muscle endocrine function, physical activity, paracrine signaling, autocrine signaling, hormone signaling, type 2 diabetes, glucose metabolism, lipid metabolism, white adipose tissue browning, bone formation, endothelial function, muscle hypertrophy, skin anatomy, tumor growth, exercise medicine, exercise biomarkers, neurodegenerative diseases
- MeSH terms
- Brain, Diabetes Mellitus, Humans, Neoplasms, Exercise, Cytokines, Muscle, Skeletal, Neurodegenerative Diseases, Muscle Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
