Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Jason R. Berggren (Creator)

Kristen Boyle (Creator)

Dustin S. Hittel (Creator)

Joseph A. Houmard (Creator)

Jane Shearer (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: 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/m2; homeostasis model assessment [HOMA] 3.6 1.0) relative to lean healthy subjects (BMI 25.7 3.2 kg/m2; 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 less than 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 (r2 = 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. Originally published Diabetes Vol. 58 No. 1 Jan 2009

Additional Information

Publication

Other

Diabetes. 58:1(January 2009) p. 30-38.

Language: English

Date: 2011

Keywords

Obesity, myostatin, skeletal muscle biomarkers

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