Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2003
Publication Date: 7/23/2003
Citation: Ramsay, T.G. 2003. Porcine leptin inhibits protein breakdown and stimulates fatty acid oxidation in C2C12 myotubes. Journal of Animal Science 81(12):3046-3051. 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. Fatty acid and amino acid metabolism were evaluated in response to recombinant pig leptin treatment. Fatty acid utilization was enhanced by chronic pig leptin treatment. Muscle protein synthesis was unaffected by leptin supplementation. 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 leptin treatment partitions energy for muscle use and reduces protein turnover. Cultures of C2C12 myotubes were used to assess - 14C-palmitate oxidation following acute (4 hour) or chronic (>20 hours) exposure to recombinant pig leptin. Acute leptin treatment had no effect on palmitate oxidation (P>0.05), while chronic leptin treatment resulted in up to a 26% increase in palmitate oxidation (P<0.05). Protein synthesis in myotubes, as measured by 3H tyrosine incorporation, was unaffected by pig leptin treatment. Protein breakdown in C2C12 myotubes, as measured by 3H-tyrosine release, was inhibited by pig leptin treatment. A leptin concentration of 0.5 ng/ml was sufficient to inhibit 3H-tyrosine release by 3.6%(P<0.05). Dexamethasone (1 uM) was used to maximally stimulate protein breakdown. Leptin (50 ng leptin/mL) reduced dexamethasone induced 3H-tyrosine release by 32% (P < 0.05). The inhibition of 3H-tyrosine release in C2C12 myotubes suggests leptin produces a protein sparing effect in vivo by inhibiting protein breakdown.