Influence of Gender, Obesity, and Muscle Lipase Activity on Intramyocellular Lipids in Sedentary Individuals
Influence of Gender, Obesity, and Muscle Lipase Activity on Intramyocellular Lipids in Sedentary Individuals
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DOI：
10.1210/jc.2009-0053
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发表时间：
2009-09-01
影响因子：
5.8
通讯作者：
Smith, Steven R.
中科院分区：
文献类型：
--
作者：
Moro, Cedric;Galgani, Jose E.;Smith, Steven R.
背景：肥胖和2型糖尿病与细胞内脂质（IMCLs）升高和胰岛素抵抗相关。目的：验证骨骼肌脂肪酶活性可能影响IMCL含量（包括二酰基甘油和神经酰胺）的假设。设计和患者：本研究包括48名年龄（19-68岁）和体重指数（20-45 kg/m(2)）不等的受试者，他们接受了骨骼肌活检、双能x线吸收仪和高胰岛素正糖钳。主要观察指标：在股外侧肌活检中，通过高胰岛素钳法测定胰岛素敏感性，测定细胞内三酰甘油（IMTG）、二酰甘油（DAG）和神经酰胺含量，以及三酰甘油和二酰甘油水解酶活性。用h -1磁共振波谱法测定25例亚组的IMCL。进行多元回归分析，以确定IMCL的主要预测因素。结果：体脂是IMTG的主要预测因子，与方法和肌肉类型无关；IMTG浓度在女性中高于男性，在肥胖受试者中高于非肥胖受试者。肥胖和2型糖尿病患者的肌肉DAG和神经酰胺浓度升高，与体脂和空腹游离脂肪酸无关，而与二酰基甘油水解酶与三酰基甘油水解酶活性（三酰基甘油不完全水解指数）的比例直接相关，这分别解释了54%和38%的DAG和神经酰胺差异（P < 0.001）。DAG含量是胰岛素抵抗的主要决定因素。结论：这些数据表明，细胞内DAG是人类胰岛素抵抗的独立预测因子，其水平与骨骼肌中脂溶酶活性相关，但与肥胖标志物无关。[J] .中华内分泌杂志，2009,31(4):347 - 347。
Context: Obesity and type 2 diabetes are associated with elevated intramyocellular lipids (IMCLs) and insulin resistance.Objective: We tested the hypothesis that skeletal muscle lipases activity could influence IMCL content (including diacylglycerol and ceramides).Design and Patients: The present study included 48 subjects with a wide range of age (19-68 yr) and body mass index (20-45 kg/m(2)) who underwent skeletal muscle biopsy, dual-energy x-ray absorptiometry and a hyperinsulinemic euglycemic clamp.Main Outcome Measures: Insulin sensitivity by hyperinsulinemic clamp, and intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramides content, and triacylglycerol and diacylglycerol hydrolase activities were measured in biopsies of vastus lateralis. IMCL was measured by H-1-magnetic resonance spectroscopy in a subgroup of 25 subjects. Multivariate regression analyses were performed to identify the main predictors of IMCL.Results: Body fat was the main predictor of IMTG independently of the method and the type of muscle; IMTG concentration was higher in females vs. males and obese vs. nonobese subjects. Muscle DAG and ceramides concentrations were elevated in obese and type 2 diabetic subjects and were not related to body fat and fasting free fatty acids, whereas a direct association with the ratio of diacylglycerol hydrolase to triacylglycerol hydrolase activity (an index of incomplete triacylglycerol hydrolysis) was observed, which explained 54 and 38% of the variance in DAG and ceramides (P < 0.001), respectively. DAG content was the main determinant of insulin resistance.Conclusions: These data suggest that intramyocellular DAG is an independent predictor of insulin resistance in humans and that its levels correlate with lipolytic enzymes activity in skeletal muscle but not with markers of adiposity. (J Clin Endocrinol Metab 94: 3440-3447, 2009)