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Title: PREVENTION OF HIGH-FAT DIET INDUCED INSULIN RESISTANCE BY TRANSGENIC INTERRUPTION OF MYOSTATIN FUNCTION IN MICE

Author
item ZHAO, BAOPING - UNIV OF HAWAII
item Wall, Robert
item YANG, JINZENG - UNIV OF HAWAII

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 12/12/2004
Publication Date: 2/5/2005
Citation: Zhao, B., Wall, R.J., Yang, J. 2005. Prevention of high-fat diet induced insulin resistance by transgenic interruption of myostatin function in mice [abstract]. North American Association for the Study of Obesity.

Interpretive Summary:

Technical Abstract: Myostatin (MSTN), a member of TGF-B family of growth factors, negatively regulates muscle development. Previously, mouse myostatin's function was interrupted by over-expressing MSTN's prodomain in skeletal muscle, resulting in a significant increase in muscle mass (Yang, et al., Mol. Rep. Dev 60: 351-61). High-fat diets are well known risk factors for obesity and insulin resistance. Since skeletal muscle is the primary target tissue for insulin-mediated glucose disposal, we hypothesized that enhanced muscularity of the MSTN-prodomain transgenic mice would prevent high-fat diet induced insulin resistance. Twelve-week-old MSTN pro-domain transgenic (TG) and littermate sex-matched wild-type (WT) male mice were randomly assigned to receive high-fat diet (45% Kcal% fat) for twelve weeks. At 24 weeks of age, TG mice showed enhanced muscle growth, and had normal blood glucose and insulin level while littermate WT mice developed hyperglycemia (fasting blood glucose: 118 vs. 135 mg/dl, P<0.01, n=10) and hyperinsulinemia (fasting serum insulin: 1180 vs 600 pg/ml, P<0.01, n=12). At 1 h after an insulin challenge, the percentage decrease of blood glucose of the TG mice was significantly lower than that of the WT mice (47% vs. 91%, P<0.01, n=8). On the glucose tolerance test, TG mice fed a high-fat diet also showed a greater ability to handle a glucose challenge (1mg D-glucose/g body weight) than the WT mice. Clearly, the results provide evidences to support our hypothesis. Enhanced skeletal muscle development by interruption of myostatin functionality can support proper insulin performance in animals fed with high-fat diet. The results also suggest that skeletal muscle development at the early stage plays an important role in preventing diet-induced insulin resistance in adults.