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

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    Author
    Hittel, Dustin S.; Berggren, Jason R.; Shearer, Jane; Boyle, Kristen E.; Houmard, Joseph A.
    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
    URI
    http://hdl.handle.net/10342/3300
    Subject
     Obesity; Myostatin; Skeletal muscle biomarkers 
    Date
    2009-01
    Citation:
    APA:
    Hittel, Dustin S., & Berggren, Jason R., & Shearer, Jane, & Boyle, Kristen E., & Houmard, Joseph A.. (January 2009). Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women. Diabetes, 58(1), 30- 38. Retrieved from http://hdl.handle.net/10342/3300

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Hittel, Dustin S., and Berggren, Jason R., and Shearer, Jane, and Boyle, Kristen E., and Houmard, Joseph A.. "Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women". Diabetes. 58:1. (30-38), January 2009. September 23, 2023. http://hdl.handle.net/10342/3300.
    Chicago:
    Hittel, Dustin S. and Berggren, Jason R. and Shearer, Jane and Boyle, Kristen E. and Houmard, Joseph A., "Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women," Diabetes 58, no. 1 (January 2009), http://hdl.handle.net/10342/3300 (accessed September 23, 2023).
    AMA:
    Hittel, Dustin S., Berggren, Jason R., Shearer, Jane, Boyle, Kristen E., Houmard, Joseph A.. Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women. Diabetes. January 2009; 58(1): 30-38. http://hdl.handle.net/10342/3300. Accessed September 23, 2023.
    Collections
    • Kinesiology
    Publisher
    East Carolina University

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