Adipocyte differentiation-related protein in human skeletal muscle: Relationship to insulin sensitivity
Adipocyte differentiation-related protein in human skeletal muscle: Relationship to insulin sensitivity
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DOI：
10.1038/oby.2005.160
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发表时间：
2005-08-01
期刊：
影响因子：
--
通讯作者：
Henry, RR
中科院分区：
文献类型：
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作者：
Phillips, SA;Choe, CC;Henry, RR
目的：为了确定脂肪细胞分化相关蛋白（ADRP）（一种结合并螯合细胞内脂肪酸的脂滴相关蛋白）是否1）在人骨骼肌中表达和2）在从肥胖非糖尿病（OND）和肥胖糖尿病（OD）受试者获得的人骨骼肌中差异调节。10例OND受试者和15例OD受试者接受了体重减轻或药物干预计划，以改善胰岛素敏感性。在基线和研究完成时测定人体测量数据、血红蛋白A（1C）、空腹血糖、血脂和葡萄糖处置率。在空腹状态下从OND和OD受试者中获得股外侧肌（SkM）活检。结果：ADRP在OND（4.4 ± 1.54 Au/10 μ g，蛋白，n = 10）和OD（5.02 ± 1.33 Au/10 μ g，n = 12）患者的SkM中有高表达。体重减轻的OND受试者甘油三酯水平降低，胰岛素作用改善。SkM ADRP含量随体重减轻从5.14 +/- 2.15 Au/10 μ g增加至9.92 +/- 1.57 Au/10 μ g（p < 0.025）。OD受试者接受曲格列酮或二甲双胍联合格列本脲治疗3 - 4个月。两种治疗达到了相似的血糖控制水平。具有较低基线ADRP含量（2.85 +/-1.07 Au/10 μ g，n = 6）的OD受试者显示ADRP表达上调（至9.27 +/-2.76 Au/10 μ g，p < 0.025）。ADRP的上调可以起到将脂肪酸作为甘油三酯隔离在离散脂滴中的作用，这可以保护肌肉免受脂肪酸对胰岛素作用和葡萄糖耐量的不利影响。
Objective: To determine whether adipocyte differentiation-related protein (ADRP), a lipid droplet-associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non-diabetic (OND) and obese diabetic (OD) subjects.Research Methods and Procedures: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A(1C), fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting.Results: ADRP was highly expressed in SkM from OND (4.4 +/- 1.54 AU/10 mu g, protein, n = 10) and OD (5.02 +/- 1.33 AU/10 mu g, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 +/- 2.15 AU/10 mu g to 9.92 +/- 1.57 AU/10 mu g (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 +/- 1.07 AU/10 mu g, n = 6) displayed up-regulation of ADRP expression (to 9.27 +/- 2.76 AU/10 mu g, p < 0.025).Discussion: ADRP is the predominant lipid droplet-associated protein in SkM, and low ADRP expression is upregulated in circumstances of improved glucose tolerance. Up-regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.