Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin resistant men. Design: In a single-blinded randomized crossover study, 10 insulin resistant men consumed three high-fat mixed-meals (2.6MJ). Meals were high in saturated FA (SFA), in monounsaturated FA (MUFA) or in polyunsaturated FA (PUFA). Fasting and postprandial skeletal muscle FA handling were examined by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and FFA in the circulation and [U-13C]-palmitate was added to the meal to label chylomicron-TAG. Skeletal muscle biopsies were taken to assess intramuscular lipid metabolism and gene expression. Results: Insulin and glucose responses (AUC) after SFA meal were significantly higher compared with PUFA meal (p=0.003 and 0.028, respectively). Uptake of TAG-derived FA was significantly lower in the early postprandial phase after PUFA meal as compared with other meals (AUC60-120, p<0.001). The PUFA meal induced less transcriptional downregulation of oxidative pathways compared with other meals. The fractional synthetic rate was higher in DAG and PL fraction after MUFA and PUFA meal. Conclusion: Intake of a PUFA meal reduced TAG-derived skeletal muscle FA uptake, which was accompanied by higher postprandial insulin sensitivity and a tendency towards a higher muscle lipid turnover. These data suggest that the effects of replacement of SFA by PUFA may contribute to less muscle lipid uptake and may be therefore protective against the development of insulin resistance. Keywords: expression profiling by array randomized crossover dietary intervention study

膳食脂肪质量可影响骨骼肌脂质代谢与脂肪堆积，进而调节胰岛素敏感性。研究目的：探究不同脂肪酸（Fatty Acid, FA）组成的膳食对肥胖胰岛素抵抗男性的骨骼肌脂肪酸代谢及餐后胰岛素敏感性的急性影响。研究设计：本研究为单盲随机交叉试验，共纳入10名胰岛素抵抗男性受试者，使其进食3种高脂混合膳食（能量为2.6兆焦），分别富含饱和脂肪酸（Saturated FA, SFA）、单不饱和脂肪酸（Monounsaturated FA, MUFA）以及多不饱和脂肪酸（Polyunsaturated FA, PUFA）。通过测量前臂骨骼肌的动静脉浓度差，评估空腹及餐后状态下的骨骼肌脂肪酸代谢情况。经静脉输注[2H2]-棕榈酸以标记循环中的内源性三酰甘油（Triacylglycerol, TAG）与游离脂肪酸（Free Fatty Acid, FFA），并在膳食中添加[U-13C]-棕榈酸以标记乳糜微粒三酰甘油。采集骨骼肌活检样本以评估肌内脂质代谢与基因表达情况。研究结果：相较于多不饱和脂肪酸膳食组，饱和脂肪酸膳食组的胰岛素与葡萄糖应答曲线下面积（AUC）显著更高（分别为p=0.003与p=0.028）。在餐后早期阶段，多不饱和脂肪酸膳食组的三酰甘油源性脂肪酸摄取量显著低于其余两组（AUC60-120，p<0.001）。相较于其余膳食组，多不饱和脂肪酸膳食对氧化通路的转录下调程度更弱。在单不饱和脂肪酸与多不饱和脂肪酸膳食组中，二酰甘油（Diacylglycerol, DAG）与磷脂（Phospholipid, PL）组分的分数合成率更高。研究结论：摄入多不饱和脂肪酸膳食可降低骨骼肌对三酰甘油源性脂肪酸的摄取量，同时伴随更高的餐后胰岛素敏感性，且呈现出更高的肌肉脂质周转趋势。上述数据表明，用多不饱和脂肪酸替代饱和脂肪酸可减少肌肉脂肪酸摄取，或可对胰岛素抵抗的发生起到预防作用。关键词：阵列表达谱分析、随机交叉膳食干预研究