Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 18, 2001
Publication Date: N/A
Interpretive Summary: Leptin is a hormone synthesized and secreted by adipocytes. Leptin has numerous roles in regulating feed intake, metabolism, reproduction and immune function. A muscle cell line was used to evaluate the potential mechanism of how chronic leptin treatment spares muscle protein, at the expense of fat during severe weight loss. Glucose and amino acid metabolism were evaluated in response to short term or long term leptin treatment. Glucose utilization was enhanced by chronic leptin treatment. Muscle protein synthesis was unaffected by leptin but protein synthesis in the muscle precursor cells was stimulated by leptin. The most significant finding was that leptin inhibits muscle protein breakdown. These muscle cells were very sensitive to leptin's inhibitory action on protein breakdown. This suggests that leptin might be useful as a partitioning agent to enhance body composition in animals or humans suffering from wasting diseases.
Technical Abstract: The present study was designed to evaluate the potential mechanism(s) by which chronic leptin treatment partitions energy for muscle use and reduces protein turnover. Cultures of C2C12 myotubes were used to assess [U]- 14C- glucose oxidation following acute (4 hour) or chronic (>20 hours) exposure to leptin. Acute leptin treatment had no effect on glucose oxidation (P>0.05), while chronic leptin treatment resulted in up to a 130% increase in glucose oxidation (P<0.05). Protein synthesis in myotubes, as measured by 3H tyrosine incorporation, was unaffected by acute or chronic leptin treatment. However, protein synthesis in C2C12 myoblasts was responsive to leptin with the highest rate of incorporation at 50 ng leptin/ml medium (P<0.05). Protein breakdown in C2C12 myotubes, as measured by 3H-tyrosine release, was inhibited by either acute or chronic leptin treatment. A leptin concentration of 0.5 ng/ml was sufficient to inhibit 3H-tyrosine release (P<0.05). The protein sparing effect of leptin in C2C12 myotubes occurs with either chronic or acute exposure and suggests leptin directly affects inhibition of protein breakdown.