Increased secretion and expression of myostatin in skeletal muscle from extremely obese women
Open accessAbstract
OBJECTIVE: Obesity is associated with endocrine abnormalities that predict the progression of insulin resistance to type 2 diabetes. Because skeletal muscle has been shown to secrete proteins that could be used as biomarkers, we characterized the secreted protein profile of muscle cells derived from extremely obese (BMI 48.8 +/- 14.8 kg/m(2); homeostasis model assessment [HOMA] 3.6 +/- 1.0) relative to lean healthy subjects (BMI 25.7 +/- 3.2 kg/m(2); HOMA 0.8 +/- 0.2). RESEARCH DESIGN AND METHODS: We hypothesized that skeletal muscle would secrete proteins that predict the severity of obesity. To test this hypothesis, we used a "bottom-up" experimental design using stable isotope labeling by amino acids in culture (SILAC) and liquid chromatography/mass spectometry/mass spectometry (LC-MS/MS) to both identify and quantify proteins secreted from cultured myotubes derived from extremely obese compared with healthy nonobese women. RESULTS: Using SILAC, we discovered a 2.9-fold increase in the secretion of myostatin from extremely obese human myotubes. The increased secretion and biological activity of myostatin were validated by immunoblot (3.16 +/- 0.18, P < 0.01) and a myoblast proliferation assay using conditioned growth medium. Myostatin was subsequently shown to increase in skeletal muscle (23%, P < 0.05) and plasma (35%, P < 0.05) and to correlate (r(2) = 0.6, P < 0.05) with the severity of insulin resistance. CONCLUSIONS: Myostatin is a potent antianabolic regulator of muscle mass that may also play a role in energy metabolism. These findings show that increased expression of myostatin in skeletal muscle with obesity and insulin resistance results in elevated circulating myostatin. This may contribute to systemic metabolic deterioration of skeletal muscle with the progression of insulin resistance to type 2 diabetes.
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Myostatin mRNA levels increase substantially in genetically modified obese mice (leptin-deficient ob/ob) and in mice receiving a high-fat diet.
“Myostatin mRNA levels increase substantially in genetically-modified obese mice (leptin-deficient ob/ob mice) and also in those receiving a high fat diet (HFD)”
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 Hittel et al., 2009
The Discussion (page unavailable) says previous studies found changes in myostatin mRNA in experimental models of obesity, and the Results report increased myostatin protein in extremely obese women. Our copy does not state that mRNA increased substantially in either leptin-deficient ob/ob mice or high-fat-diet mice. (LLM, conf=0.78)
Experimental — accuracy not yet measuredCirculating and skeletal muscle myostatin levels are present in obese subjects compared to non-obese subjects.
“so both circulating and SkM myostatin levels are present in obese subjects when compared to non-obese subjects (Allen et al., 2008; Hittel et al., 2009).”
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 Hittel et al., 2009
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“Myostatin mRNA levels increase substantially in genetically-modified obese mice (leptin-deficient ob/ob mice) and also in those receiving a high fat diet (HFD), so both circulating and SkMmyostatin levels are present in obese subjects when compared to non-obese subjects (Allen et al., 2008; Hittel et al., 2009).”
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- Authors
- Hittel, D. S., Berggren, J. R., Shearer, J., Boyle, K., & Houmard, J. A.
- Affiliations
- University of Calgary (CA)
- East Carolina University (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2009-01-01
- Volume
- 58
- Issue
- 1
- Pages
- 30-38
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2606890
- OpenAlex
- W2132813206
- Cited by
- 324
- References
- 47
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 12 · 2023: 18 · 2022: 19 · 2021: 21 · 2020: 20 · 2019: 14 · 2018: 26 · 2017: 13 · 2016: 11 · 2015: 25 · 2014: 31 · 2013: 24 · 2012: 22
- FWCI
- 5.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- The Scholarship East Carolina University's Institutional Repository (East Carolina University) (submittedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Diabetes Association
- Fondation pour la Recherche Médicale
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK056112)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- myostatin, obesity, insulin resistance, skeletal muscle, myotubes, secreted proteins, type 2 diabetes, myoblast proliferation, energy metabolism, women
- MeSH terms
- Adult, Chromatography, Liquid, Female, Humans, Insulin Resistance, Middle Aged, Obesity, Immunoblotting, Muscle, Skeletal, Muscle Fibers, Skeletal, Tandem Mass Spectrometry, Myostatin
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