Insulin activation of plasma nonesterified fatty acid uptake in metabolic syndrome.
Insulin activation of plasma nonesterified fatty acid uptake in metabolic syndrome.
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DOI：
10.1161/atvbaha.112.250019
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Parks EJ
中科院分区：
文献类型：
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作者：
Ramos-Roman MA;Lapidot SA;Phair RD;Parks EJ
长期以来，胰岛素对脂肪酸代谢的控制被认为是由脂肪分解的抑制所主导的。这项研究的目的是检验胰岛素的这种单一作用不足以解释观察到的脂肪酸动力学的假设。在超重人类受试者（n=15，BMI 35.8 ± 7.1 kg/m2）中，在膳食耐受试验期间测量脂肪酸动力学，并通过IVGTT评估胰岛素敏感性。非稳态示踪剂动力学模型使用ProcessDB ®软件制定和测试。单独抑制脂肪释放不能解释餐后NEFA浓度的变化，但当与胰岛素激活脂肪酸摄取相结合时，与NEFA数据一致。观察到的NEFA摄取的胰岛素Km与葡萄糖摄取的胰岛素敏感性（IVGTT Si）（r=-0.626，P=0.01）和餐后全身脂肪氧化（r=-0.538，P=0.05）呈负相关。这些结果支持胰岛素通过释放和摄取机制调节脂肪酸周转。脂肪酸摄取的激活与人类数据一致，在细胞培养中具有机制先例，并突出了旨在改善胰岛素抵抗疾病状态中脂肪酸代谢控制的治疗的新的潜在靶点。
Insulin control of fatty acid metabolism has long been deemed dominated by suppression of adipose lipolysis. This study’s goal was to test the hypothesis that this single role of insulin is insufficient to explain observed fatty acid dynamics. Fatty acid kinetics were measured during a meal-tolerance test and insulin sensitivity assessed by IVGTT in overweight human subjects (n=15, BMI 35.8 ± 7.1 kg/m2). Non-steady state tracer kinetic models were formulated and tested using ProcessDB© software. Suppression of adipose release alone could not account for NEFA concentration changes postprandially, but when combined with insulin activation of fatty acid uptake was consistent with the NEFA data. The observed insulin Km for NEFA uptake was inversely correlated with both insulin sensitivity of glucose uptake (IVGTT Si) (r=−0.626, P=0.01), and whole body fat oxidation after the meal (r=−0.538, P=0.05). These results support insulin regulation of fatty acid turnover by both release and uptake mechanisms. Activation of fatty acid uptake is consistent with the human data, has mechanistic precedent in cell culture, and highlights a new potential target for therapies aimed at improving the control of fatty acid metabolism in insulin-resistant disease states.