Bickerton A S T, Roberts R, Fielding B A, Tornqvist H, Blaak E E, Wagenmakers A J M, Gilbert M, Humphreys S M, Karpe F, Frayn K N
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK.
Diabetologia. 2008 Aug;51(8):1466-74. doi: 10.1007/s00125-008-1040-x. Epub 2008 May 27.
AIMS/HYPOTHESIS: Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BMI 25-35 kg/m2).
In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n = 124) and in men with fasting insulin below the median (n = 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls.
In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 micromol/l; controls, 445 micromol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p < 0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p = 0.02, and 44%, p = 0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p = 0.03).
CONCLUSIONS/INTERPRETATION: Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.
目的/假设：游离脂肪酸（NEFA）生成增加及浓度升高可能是胰岛素抵抗的潜在原因。我们研究了胰岛素抵抗超重男性（体重指数25 - 35kg/m²）的全身及脂肪组织NEFA代谢情况。
在一项队列研究中，我们检测了空腹胰岛素处于上四分位数的男性（n = 124）以及空腹胰岛素低于中位数的男性（n = 159）的NEFA浓度。在一项代谢研究中，我们检测了10名胰岛素抵抗男性和10名对照者在空腹和餐后状态下的NEFA代谢情况。
在队列研究中，两组间空腹NEFA浓度无显著差异（中位数：胰岛素抵抗男性为410微摩尔/升；对照组为445微摩尔/升）。然而，甘油三酯浓度差异显著（分别为1.84与1.18毫摩尔/升，p < 0.001）。在代谢研究中，两组间动脉NEFA浓度同样无差异，而胰岛素抵抗男性的甘油三酯浓度显著更高。与对照组相比，胰岛素抵抗男性单位脂肪量的全身NEFA生成及皮下脂肪组织NEFA释放均减少（空腹值分别降低32%，p = 0.02，以及44%，p = 0.04）。肝脂肪氧化和生酮指标3 - 羟基丁酸浓度较低（p = 0.03）。
结论/解读：在胰岛素抵抗状态下，脂肪组织NEFA输出（每单位组织重量）并未增加。相反，似乎被高空腹胰岛素浓度所抑制。甘油三酯代谢的改变比NEFA代谢更为显著，表明肝脏中脂肪酸代谢分配发生改变（氧化减少，酯化增加）。
