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
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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.
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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
Items 601–700 of 1,000
Small Extracellular Vesicles Derived From Damaged Muscle Aggravate Kidney Injury Progression
Jiang, S., Kang, S., Kwon, O., Seo, W., Jin, E., Ha, H., & Huh, J. Y. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13861 · Cited by 5
Xiang, L., Zhou, B., Luo, Y., Bi, H., Lü, Y., & Zhou, J. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003525 · Cited by 5
Irisin Prevents the Effects of Simulated Microgravity on Bone and Muscle Differentiation Markers
Sanesi, L., Zerlotin, R., Campiolo, A., Oranger, A., Dicarlo, M., Suriano, C., Ghadiri, A., Colaianni, G., Grano, M., Tavella, S., et al. (2025) · FASEB BioAdvances · doi:10.1096/fba.2025-00085 · Cited by 4
“Myokines exert beneficial effects on multiple organs and tissues in autocrine, paracrine, and endocrine manners [23, 24].”
A comprehensive model for the converging biologies that underpin the homeostatic sleep signal
Fernandez, F., & Grandner, M. A. (2025) · Sleep Medicine · doi:10.1016/j.sleep.2025.106723 · Cited by 4
Sotomayor, E. M., Espinoza-Salinas, A., Arenas-Sánchez, G., de la Fuente, F. P., León-Prados, J. A., & González-Jurado, J. A. (2021) · Sustainability · doi:10.3390/su13147687 · Cited by 6
“Myokine signalling mediates the muscle–brain endocrine loop, promoting relationship building between muscles and the brain, and could improve brain functions such as cognition, memory, and motor coordination [59,62].”
BackgroundVasodilator Dysfunction in Human Obesity: Established and Emerging Mechanisms
Schinzari, F., Tesauro, M., & Cardillo, C. (2021) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000001108 · Cited by 5
Poder del músculo esquelético en la salud y enfermedad
Matsudo, S. M. (2021) · Revista de Nutrición Clínica y Metabolismo · doi:10.35454/rncm.v4n4.288 · Cited by 4
Bratičević, M. N., Žarak, M., Šimac, B., Perović, A., & Dumić, J. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1074061 · Cited by 4
High-Fat and High-Sucrose Diet Leads to Skeletal Muscle Loss and Bladder Dysfunction in Rat
Wada, N., Abe, N., Miyauchi, K., Makino, S., & Κakizaki, H. (2023) · Research and Reports in Urology · doi:10.2147/rru.s406808 · Cited by 4
Nachit, M., Burgio, M. D., Abyzov, A., Garteiser, P., Paradis, V., Vilgrain, V., Leclercq, I. A., & BEERS, B. E. V. (2023) · European Radiology · doi:10.1007/s00330-023-10131-2 · Cited by 5
“A muscle-to-liver axis could operate via multiple mechanisms, e.g., the modulation of metabolic flux and the release of myokines or extracellular vesicles [52–54].”
Kang, G.-A., Shin, J., & Yoon, J. (2023) · Research in Community and Public Health Nursing · doi:10.12799/rcphn.2023.00164 · Cited by 4
Sarcopenia and Coronary Microvascular Dysfunction
Schindler, T. H., & Peterson, L. R. (2023) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2023.09.008 · Cited by 4
Kim, J., McKenna, C. F., Askow, A. T., Salvador, A. F., Scaroni, S. E., Cerna, J., Cannavale, C. N., Paluska, S. A., Lisio, M. D., Petruzzello, S. J., et al. (2024) · Journal of Cognitive Enhancement · doi:10.1007/s41465-024-00285-2 · Cited by 4
“Exercise-sensitive secreted biomarkers, such as BDNF and CTSB, are also referred to as “exerkines” or, if synthesized from skeletal muscle in response to muscular contractions, “myokines” (Severinsen & Pedersen, 2020).”
Wang, S., Li, J., & Zhao, Y. (2024) · PLoS ONE · doi:10.1371/journal.pone.0297848 · Cited by 4
Diabetes Pharmacotherapy and its effects on the Skeletal Muscle Energy Metabolism
Yu, B., Wang, D., Zhou, J., Huang, R., Cai, T., Hu, Y., Zhou, Y., & Ma, J. (2024) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575299439240216081711 · Cited by 5
Svensson, M., Lovrić, A., Åkerfeldt, T., Hellsten, D., Haas, T. L., Gustafsson, T. P., & Rullman, E. (2024) · Physiological Reports · doi:10.14814/phy2.15995 · Cited by 4
“Numerous circulating hormones (Hackney & Lane, 2015), metabolites, or myokines (Severinsen & Pedersen, 2020) released from SM are plausible candidates.”
BackgroundRoles of natural products on myokine expression and secretion in skeletal muscle atrophy
Zhaoyu, L., Xiaomeng, Y., Na, L., Shang, J., Du, G., & Xiuying, Y. (2024) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2024.114550 · Cited by 4
Role of Myostatin in Rheumatoid Arthritis: A Review of the Clinical Impact
González-Ponce, F., Ramírez-Villafaña, M., Gómez-Ramírez, E. E., Saldaña-Cruz, A. M., Gallardo-Moya, S. G., Rodriguez-Jimenez, N. A., Jacobo-Cuevas, H., Nava-Valdivia, C. A., Avalos-Salgado, F. A., Totsuka-Sutto, S. E., et al. (2024) · Diagnostics · doi:10.3390/diagnostics14111085 · Cited by 4
“Myokines modulate the proliferation, differentiation, and regeneration of muscle fibers in the presence or absence of physical exercise [47].”
BackgroundAre Aminoglycoside Antibiotics TRPing Your Metabolic Switches?
Franco‐Obregón, A., & Tai, Y. K. (2024) · Cells · doi:10.3390/cells13151273 · Cited by 5
Stenbäck, V., Lehtonen, I., Mäkelä, K. A., Raza, G. S., Ylinen, V. P., Valtonen, R. I. P., Hamari, T., Walkowiak, J., Tulppo, M. P., & Herzig, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179135 · Cited by 4
“IL-6 increases basal glucose uptake, lipolysis, and fat oxidation via activation of adenosine 5 ′ -monophosphate-activated protein kinase (AMPK) [36].”
BackgroundInteractions between muscle volume and body mass index on brain structure in the UK Biobank
Lu, A., Than, S., Beare, R. J., Hood, A. L., Collyer, T. A., Srikanth, V. K., & Moran, C. (2024) · Frontiers in Dementia · doi:10.3389/frdem.2024.1456716 · Cited by 4
“…unclear, but skeletal muscle is increasingly recognized for its role in cognitive function, possibly through myokines and myometabolites that reduce neuroinflammation, improve brain glucose metabolism, and enhance tissue oxidative capacity (Rai and Demontis, 2022; Severinsen and Pedersen, 2020).”
BackgroundAmore, E., Cenni, V., Piazzi, M., Signore, M., Orlandi, G., Neri, S., Biressi, S., Barone, R., Felice, V. D., Follo, M. Y., et al. (2024) · Biomolecules · doi:10.3390/biom14101243 · Cited by 5
“Some of these proteins (i.e., osteoglycin and decorin) are already known for being involved in bone remodeling [7,8].”
BackgroundLi, Q., Li, C., & Zhang, X. (2024) · Cellular and molecular neurobiology · doi:10.1007/s10571-024-01497-y · Cited by 5
“In addition, EX is also one of the key ways to promote BDNF secretion (Severinsen and Pedersen 2020).”
BackgroundDiet and exercise in relation to lower extremity artery disease
Blinc, A., Paraskevas, K. I., Stanek, A., Jawień, A., Antignani, P. L., Mansilha, A., Mikhailidis, D. P., & Poredoš, P. (2024) · International Angiology · doi:10.23736/s0392-9590.24.05310-0 · Cited by 4
Myogenic Classical Endocannabinoids, Their Targets and Activity
Balezina, O. P., Tarasova, E. O., & Bogacheva, P. O. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924100080 · Cited by 4
Autologous myokine-loaded pre-vascularized bioactive scaffold enhances bone augmentation
Wang, C., Qiu, Y., Yang, Y., Dai, Q., Cao, X., Shao, L., & Zhao, F. (2024) · Composites Part B Engineering · doi:10.1016/j.compositesb.2024.111967 · Cited by 4
Impact of aerobic exercise on brain metabolism: Insights from spatial metabolomic analysis
Zheng, J., Luo, W., Kong, C., Xie, W., Chen, X., Qiu, J., Wang, K., Wei, H., & Zhou, Y. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115339 · Cited by 4
Transcriptomic adaptation of skeletal muscle in response to MICT and HIIT exercise modalities
Hong, W., Luan, Y., Zheng, J., Xiong, Y., Zhang, B., & Ma, Y. (2025) · PLoS ONE · doi:10.1371/journal.pone.0318782 · Cited by 5
“Skeletal muscle transcriptomic adaptations to MICT and HIIT metabolism, energy metabolism, and overall health [16,17].”
Ambroszkiewicz, J., Chełchowska, M., Mazur, J., Rowicka, G., Klemarczyk, W., Strucińska, M., & Gajewska, J. (2025) · Nutrients · doi:10.3390/nu17050834 · Cited by 4
“Myostatin (MSTN), a well-characterized negative regulator of muscle growth, inhibits muscle development by activating pathways that promote protein degradation and suppress muscle cell proliferation [8–10].”
McNeish, B. L., Miljkovic, I., Allison, M., Hughes, T. M., Nasrallah, I. M., Terkpertey, E., & Rosano, C. (2025) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2025.105823 · Cited by 4
Walking Speed and Risk of Cancer in Two Prospective Cohort Studies
Mak, J. K. L., Tan, K. C. B., Jylhävä, J., Hägg, S., & Cheung, C. (2025) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13792 · Cited by 5
Longitudinal association between leisure-time physical activity and vascular elasticity indices
Szaló, G., Hellgren, M. I., Allison, M., Råstam, L., Lindblad, U., & Daka, B. (2021) · BMC Cardiovascular Disorders · doi:10.1186/s12872-021-01911-z · Cited by 8
SMART approaches for genome-wide analyses of skeletal muscle stem and niche cells
Blackburn, D. M., Lazure, F., & Soleimani, V. D. (2021) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2021.1908950 · Cited by 4
Levy, Y. A., Ciaraldi, T. P., Mudaliar, S. R. D., Phillips, S. A., & Henry, R. R. (2022) · Adipocyte · doi:10.1080/21623945.2022.2070949 · Cited by 4
“Multiple investigators have shown that the secretion of selected myokines can be regulated by the presence of T2D (reviewed in [12,25]).”
BackgroundFang, W.-Y., Chang, W., Tsai, Y., Hsu, H., Chang, F., Lin, C., & Lo, Y. (2023) · Journal of Food and Drug Analysis · doi:10.38212/2224-6614.3435 · Cited by 4
“Evidence reveals that maintaining skeletal muscle mass is not only integral for breathing and locomotion, but is also clinically important to regulate metabolic systems [2,3].”
Functional nutrition for the health of exercising individuals and elite sportspersons
Venkata, R. K., & Meda, S. S. (2023) · Nutrition and Health · doi:10.1177/02601060231191865 · Cited by 4
“They work as autocrine, paracrine, and endocrine ways to produce the targeted effects on the various tissues (Severinsen and Pedersen, 2020).”
BackgroundKarkhut, S.-M., Muzyka, I., Savytska, M., Dzhyoieva, K., Pohoretska, Y., Іванченко, Н. О., Zayachkivska, О., Schloss, J. V., & Szabó, S. (2021) · Proceedings of the Shevchenko Scientific Society Medical Sciences · doi:10.25040/ntsh2021.02.06 · Cited by 4
Gregory, J. M., Kraft, G., Farmer, B., Smith, M. S., LaNeve, D. C., Williams, P. E., Tomasek, K., Su, Y. R., Wilson, C., Thompson, M. D., et al. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab088 · Cited by 4
“Over the past 2 decades, an increasing number of studies have revealed skeletal muscle’s role as a secretory organ, which produces and secretes numerous myokines with autocrine, paracrine, and endocrine functions [17-19].”
BackgroundHeart failure-related skeletal myopathy. Potential involvement of myokines
Latasa, I., Ramírez‐Vélez, R., Izquierdo, M., & Dı́ez, J. (2021) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2021.06.001 · Cited by 4
Baganha, R. J., Bernardes, A. C. B. E., & Antunes, L. G. (2021) · Temas em Educação e Saúde · doi:10.26673/tes.v17i00.15261 · Cited by 3
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“Currently, researchers have identi fi ed hundreds of myokines (Graf and Ferrari, 2019; Krogh and Klarlund, 2020) and are beginning to examine the role of myokines in the crosstalk between muscle and other organs, including adipose tissue, bone, liver, intestines, pancreas, blood vessels, brain, and…”
BackgroundBody Composition During Androgen Deprivation Therapy in Prostate Cancer
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Linking Circulating Irisin and Type 2 Diabetes: A Systematic Review and Meta‐Analysis
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Roles of myokines in osteoporosis under physiological and diabetic conditions
Ji, X., Hu, X., Xu, T., & Yang, W.-L. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1600218 · Cited by 5
“These molecules act in an autocrine, paracrine, or endocrine manner, in fl uencing not only muscle function but also other tissues, including bone (2, 3).”
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Chronic Alcohol and Skeletal Muscle
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“Hormonal factors, acting at the endocrine, paracrine, and autocrine level, along with nutritional interactions also should be factored into the adaptive control mechanisms (Chow et al., 2022; Nunes et al., 2022; Rennie & Tipton, 2000; Severinsen & Pedersen, 2020).”
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“39,40 Myostatin is one of the myokines produced by skeletal muscle and negatively regulates myogenesis.”
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“Muscle factors secreted by skeletal muscle are important biomarkers for monitoring cancer, diabetes, and neurodegeneration, and mass loss of skeletal muscle may reduce insulin-mediated glucose metabolism [9].”
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Background
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
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