Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice
Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice
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DOI：
10.1152/ajpendo.1999.276.5.e913
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发表时间：
1999-05-01
影响因子：
5.1
通讯作者：
Coleman, RA
中科院分区：
文献类型：
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作者：
Muoio, DM;Dohm, GL;Coleman, RA
由于肌肉三酰甘油（TAG）的积累可能有助于瘦素缺乏的ob/ob小鼠的胰岛素抵抗，我们研究了瘦素和胰岛素对从瘦和肥胖ob/ob小鼠分离的肌肉中[C-14]葡萄糖和[C-14]油酸代谢的急性（60 - 90-min）影响。瘦素使ob/ob比目鱼肌糖原合成减少36 - 46%（P <0.05），油酸氧化增加26%（P <0.05），油酸掺入TAG减少32%（P <0.05），油酸分配比（油酸分配为TAG/CO2）降低44%（P <0.05）。胰岛素使油酸氧化减少31%（P <0.05），使油酸掺入TAG增加46%（P <0.05），使油酸分配比增加125%（P <0.01）。加入瘦素会降低胰岛素的抗氧化和脂肪生成作用。在来自瘦小鼠的比目鱼肌中，胰岛素使分配比增加142%，而瘦素使其降低51%，如先前报道的（Muoio，D. M.，G. L. Dohm，F. t. Fiedorek，E. B。Tapscott和R. a.科尔曼。Diabetes 46：1360 - 1363，1997）。磷脂酰肌醇S激酶抑制剂渥曼青霉素阻断胰岛素对脂质代谢的作用，但仅减弱瘦素的作用。葡萄糖浓度从5 mM增加到10 mM并不影响TAG的合成，这表明胰岛素诱导的脂肪生成不依赖于葡萄糖摄取的增加。这些数据表明，瘦素反对胰岛素促进TAG在瘦肌肉和肥胖/肥胖肌肉中的积累。由于急性瘦素暴露不能纠正肥胖基因肥胖肌肉的胰岛素抵抗，体内葡萄糖稳态的改善似乎需要其他长期因素，可能是TAG耗竭。
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 [C-14]glucose and [C-14]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 S-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.