Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis
Open accessAbstract
Skeletal muscle plays important roles in whole-body glucose and fatty acid metabolism. However, muscle also secretes cytokines and growth factors (collectively termed myokines) that can potentially act in an autocrine, a paracrine, and/or an endocrine manner to modulate metabolic, inflammatory, and other processes. Here, we report the identification and characterization of myonectin, a novel myokine belonging to the C1q/TNF-related protein (CTRP) family. Myonectin transcript was highly induced in differentiated myotubes and predominantly expressed by skeletal muscle. Circulating levels of myonectin were tightly regulated by the metabolic state; fasting suppressed, but refeeding dramatically increased, its mRNA and serum levels. Although mRNA and circulating levels of myonectin were reduced in a diet-induced obese state, voluntary exercise increased its expression and circulating levels. Accordingly, myonectin transcript was up-regulated by compounds (forskolin, epinephrine, ionomycin) that raise cellular cAMP or calcium levels. In vitro, secreted myonectin forms disulfide-linked oligomers, and when co-expressed, forms heteromeric complexes with other members of the C1q/TNF-related protein family. In mice, recombinant myonectin administration reduced circulating levels of free fatty acids without altering adipose tissue lipolysis. Consistent with this, myonectin promoted fatty acid uptake in cultured adipocytes and hepatocytes, in part by up-regulating the expression of genes (CD36, FATP1, Fabp1, and Fabp4) that promote lipid uptake. Collectively, these results suggest that myonectin links skeletal muscle to lipid homeostasis in liver and adipose tissue in response to alterations in energy state, revealing a novel myonectin-mediated metabolic circuit.
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In the presence of carbohydrates or lipids in the gastrointestinal tract, there was potent stimulation of myonectin expression in the assessed muscles.
“It was also shown that in the presence of carbohydrates or lipids in the gastrointestinal tract there was potent stimulation of myonectin expression in the assessed muscles (Seldin et al., 2012)”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Seldin et al., 2012
Myonectin is widely expressed in skeletal muscle, more precisely in myotubes.
“The study by Seldin et al., which made a general characterization of this myokine, showed that it is widely expressed in SkM, more precisely in myotubes (Seldin et al., 2012).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Seldin et al., 2012
Myonectin (CTRP15) is a new myokine found as a protein typical of fatty acid metabolism in response to exercise.
“Myonectin, also known as C1q/TNF-related protein 15 (CTRP15), is a new myokine recently found as a protein typical of fatty acid metabolism in response to exercise (Seldin et al., 2012; Toloza et al., 2018)”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Seldin et al., 2012
Myonectin is a potent inducer of cell differentiation in C2C12 cells, indicating that it is produced in muscle fibers, not satellite cells.
“In addition, it is described as a potent inducer of cell differentiation in C2C12 cells, which, according to the authors, indicates that this protein is produced in muscle fibers, not in satellite cells (Seldin et al., 2012).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Seldin et al., 2012
In vivo, using soleus and plantaris muscles, gene expression and circulating levels of myonectin were increased in animals that had been fed compared to animals that had not.
“A test performed in vivo using the soleus and plantaris muscles showed increased gene expression and circulating levels of myonectin in animals that had been fed (compared to animals that had not).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Seldin et al., 2012
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- Authors
- Seldin, M. M., Peterson, J. M., Byerly, M. S., Wei, Z., & Wong, G. W.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Wong, G. William
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 287
- Issue
- 15
- Pages
- 11968-11980
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3320944
- OpenAlex
- W2083855314
- Cited by
- 406
- References
- 46
- Citations by year
- 2026: 27 · 2025: 27 · 2024: 33 · 2023: 30 · 2022: 34 · 2021: 32 · 2020: 44 · 2019: 35 · 2018: 31 · 2017: 22 · 2016: 24 · 2015: 20 · 2014: 22 · 2013: 19 · 2012: 5
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons - East Tennessee State University (East Tennessee State University) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-084171, T32DK007751, F32DK084607, P30DK079637, R01DK084171)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- myonectin, myokines, skeletal muscle, lipid homeostasis, free fatty acids, fatty acid uptake, adipocytes, hepatocytes, diet-induced obesity, fasting and refeeding, voluntary exercise, cAMP signaling, calcium signaling, heteromeric protein complexes, CD36, FATP1, FABP1, FABP4, energy metabolism
- MeSH terms
- Animals, Cells, Cultured, Fatty Acids, Female, Gene Expression Regulation, Glycosylation, Homeostasis, Humans, Male, Mice, Inbred C57BL, Molecular Sequence Data, Motor Activity, Muscle Proteins, Nutritional Status, Obesity, Protein Binding, Rabbits, Transcription, Genetic, Cytokines, Protein Structure, Tertiary, Muscle, Skeletal, Muscle Fibers, Skeletal, Lipid Metabolism, Mice, Adipokines, Protein Multimerization
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