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A-28 Free Communication/Poster - Muscle 1: MAY 28, 2008 7: 30 AM - 12: 30 PM: ROOM: Hall B

Leptin and Obesity Alter Expression of Myostatin and its Receptor ActRIIb in Mouse Skeletal Muscle

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Board #98 May 28 9:30 AM - 11:00 AM

Speaker, Kristin J.; Allen, David L.; Cleary, Allison S.; Lindsay, Sarah F.; Reed, Jason M.; Madden, Mollly C.

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Medicine & Science in Sports & Exercise: May 2008 - Volume 40 - Issue 5 - p S193
doi: 10.1249/01.mss.0000322295.46910.71
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Myostatin is an anti-growth factor expressed in skeletal muscle that has profound effects on the mass of both tissues. PURPOSE. In the present study, we used quantitative real-time polymerase chain reaction (QRT-PCR) to determine mRNA levels for myostatin (MSTN) and its primary receptor activin RIIb (ActRIIb) in the tibialis anterior (TA) and soleus (SOL) skeletal muscles of genetically obese leptin-deficient mice, leptin-deficient mice injected with recombinant leptin for two weeks, and in dietarily obese mice. RESULTS. TA muscle mass was significantly lower in leptin-deficient ob/ob mice but SOL mass was not significantly different between ob/ob mice and wild type C57 mice. Similarly, MSTN mRNA levels were significantly increased in TA but not the SOL of ob/ob mice compared to nonobese control mice. Interestingly, leptin injection significantly decreased MSTN mRNA levels in the TA of ob/ob mice despite the fact that it had no significant affect on TA muscle mass. ActRIIb mRNA levels were unchanged by either leptin deficiency or leptin replacement in either TA or SOL. Feeding mice a high fat diet (HFD) increased body mass and fat mass at 1 week, 1 month, and 3 months compared to age-matched littermate mice fed a normal diet (ND). TA mass was significantly increased after 1 week in HFD mice compared to ND mice but was not significantly different at 1 month or 3 months on a HFD. Soleus mass was unchanged at any timepoint. Interestingly, MSTN and ActRIIb mRNA levels in the TA were unchanged at 1 week, significantly increased at 1 month, and not significantly different at 3 months in HFD mice compared to ND mice. In the soleus MSTN mRNA levels were unchanged or slightly decreased in HFD mice but ActRIIb mRNA levels were significantly increased at 1 month on a high fat diet compared to ND mice.

CONCLUSIONS: In summary, both muscle mass and MSTN expression are altered by obesity, but the alterations (1) differ between genetically obese and dietarily obese mice; (2) differ between muscle types (TA vs. SOL), and (3) are not temporally associated. Thus MSTN expression appears to be regulated by increased fat/caloric intake, and may play a role in the regulation of muscle mass or metabolism during the obese state.

©2008The American College of Sports Medicine