Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands.
Obesity (Silver Spring). 2011 Jul;19(7):1350-9. doi: 10.1038/oby.2011.10. Epub 2011 Feb 17.
Disturbances in skeletal muscle lipid metabolism may precede or contribute to the development of whole body insulin resistance. In this study, we examined fasting and postprandial skeletal muscle fatty acid (FA) handling in insulin resistant (IR) men. Thirty men with the metabolic syndrome (MetS) (National Cholesterol Education Program-Adult Treatment Panel III) were included in this sub-study to the LIPGENE study, and divided in two groups (IR and control) based on the median of insulin sensitivity (S(I) = 2.06 (mU/l(-1))·min(-1)·10(-4)). Fasting and postprandial skeletal muscle FA handling were examined by combining the forearm balance technique with stable isotopes of palmitate. [(2)H(2)]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free FAs (FFAs) in the circulation and [U-(13)C]-palmitate was incorporated in a high-fat mixed meal (2.6 MJ, 61 E% fat) to label chylomicron-TAG. Muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid (PL) content, their fractional synthetic rates (FSRs) and degree of saturation, as well as messenger RNA (mRNA) expression of genes involved in lipid metabolism. In the first 2 h after meal consumption, forearm muscle [(2)H(2)]-labeled TAG extraction was higher in IR vs. control (P = 0.05). Fasting percentage saturation of muscle DAG was higher in IR vs. control (P = 0.016). No differences were observed for intramuscular TAG, DAG, FFA, and PL content, FSR, and muscle mRNA expression. In conclusion, increased muscle (hepatically derived) TAG extraction during postprandial conditions and increased saturation of intramuscular DAG are associated with insulin resistance, suggesting that disturbances in skeletal muscle FA handling could play a role in the development of whole body insulin resistance and type 2 diabetes.
骨骼肌脂质代谢紊乱可能先于或导致全身胰岛素抵抗的发展。在这项研究中，我们检查了胰岛素抵抗（IR）男性的空腹和餐后骨骼肌脂肪酸（FA）处理。30 名患有代谢综合征（MetS）（国家胆固醇教育计划-成人治疗小组 III）的男性被纳入 LIPGENE 研究的子研究中，并根据胰岛素敏感性的中位数（S（I）= 2.06（mU/l(-1))·min(-1)·10(-4)) 将其分为两组（IR 和对照组）。通过将前臂平衡技术与棕榈酸的稳定同位素结合，检查空腹和餐后骨骼肌 FA 处理。[（2）H（2）]-棕榈酸经静脉内输注以标记内源性三酰甘油（TAG）和循环中的游离脂肪酸（FFA），[U-（13）C]-棕榈酸掺入高脂肪混合餐（2.6 MJ，61 E%脂肪）以标记乳糜微粒-TAG。采集肌肉活检标本以确定肌肉 TAG、二酰基甘油（DAG）、FFA 和磷脂（PL）含量、其合成率（FSR）和饱和度，以及参与脂质代谢的基因的信使 RNA（mRNA）表达。在用餐后的头 2 小时内，IR 组与对照组相比，前臂肌肉中的[（2）H（2）]-标记 TAG 提取更高（P = 0.05）。IR 组的肌肉 DAG 空腹百分比饱和度高于对照组（P = 0.016）。肌肉内 TAG、DAG、FFA 和 PL 含量、FSR 和肌肉 mRNA 表达无差异。总之，餐后条件下肌肉（肝源性）TAG 提取增加和肌肉内 DAG 饱和度增加与胰岛素抵抗相关，这表明骨骼肌 FA 处理的紊乱可能在全身胰岛素抵抗和 2 型糖尿病的发展中起作用。
