Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice.
Because muscle triacylglycerol (TAG) accumulation might contribute to insulin resistance in leptin-deficient ob/ob mice, we studied the acute (60- to 90-min) effects of leptin and insulin on [14C]glucose and [14C]oleate metabolism in muscles isolated from lean and obese ob/ob mice. In ob/ob soleus, leptin decreased glycogen synthesis 36-46% (P < 0.05), increased oleate oxidation 26% (P < 0.05), decreased oleate incorporation into TAG 32% (P < 0.05), and decreased the oleate partitioning ratio (oleate partitioned into TAG/CO2) 44% (P < 0.05). Insulin decreased oleate oxidation 31% (P < 0.05), increased oleate incorporation into TAG 46% (P < 0.05), and increased the partitioning ratio 125% (P < 0.01). Adding leptin diminished insulin's antioxidative, lipogenic effects. In soleus from lean mice, insulin increased the partitioning ratio 142%, whereas leptin decreased it 51%, as previously reported (Muoio, D. M. , G. L. Dohm, F. T. Fiedorek, E. B. Tapscott, and R. A. Coleman. Diabetes 46: 1360-1363, 1997). The phosphatidylinositol 3-kinase inhibitor wortmannin blocked insulin's effects on lipid metabolism but only attenuated leptin's effects. Increasing glucose concentration from 5 to 10 mM did not affect TAG synthesis, suggesting that insulin-induced lipogenesis is independent of increased glucose uptake. These data indicate that leptin opposes insulin's promotion of TAG accumulation in lean and ob/ob muscles. Because acute leptin exposure does not correct insulin resistance in ob/ob muscles, in vivo improvements in glucose homeostasis appear to require other long-term factors, possibly TAG depletion.
D000818:Animals; D004347:Drug Interactions; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism