The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
The fatty acid transporter FAT/CD36 is upregulated in subcutaneous and visceral adipose tissues in human obesity and type 2 diabetes
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DOI：
10.1038/sj.ijo.0803212
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发表时间：
2006-06-01
影响因子：
4.9
通讯作者：
Heigenhauser, G. J. F.
中科院分区：
文献类型：
--
作者：
Bonen, A.;Tandon, N. N.;Heigenhauser, G. J. F.
背景：长链脂肪酸（LCFAs）通过一种或多种lcfa结合蛋白介导的蛋白机制穿过质膜。其中，FAT/CD36已被确定为心脏和骨骼肌中关键的LCFA转运蛋白，其受胰岛素的急性和慢性调节。在骨骼肌中，肥胖和2型糖尿病患者的FAT/CD36表达和/或亚细胞分布发生改变。关于这种蛋白的表达是否在人类肥胖或2型糖尿病的皮下和/或内脏脂肪组织库中也发生改变，目前的信息有限。目的：比较(a)瘦、超重、肥胖个体和2型糖尿病患者皮下和内脏脂肪组织库中脂肪/CD36的表达，(b)确定这些脂肪组织库中脂肪/CD36的蛋白表达是否与胰岛素抵抗的严重程度（2型糖尿病>肥胖>超重/瘦）有关，(c)脂肪组织库中脂肪/CD36蛋白表达是否与循环底物和激素的改变有关。受试者：正在接受腹部手术的受试者，他们瘦（n = 10； 3男，7女），超重（n = 10； 3男，7女）或肥胖（n = 7； 1男，6女），或被诊断患有2型糖尿病（n = 5； 1男，4女）参加了这项研究。测量方法：在全身麻醉下获得受试者皮下和内脏脂肪组织样本以及血液样本。使用Western blotting分析脂肪组织样本的FAT/CD36。分析血清中葡萄糖、胰岛素、游离脂肪酸和瘦素含量。还计算了BMI。结果：超重、肥胖和2型糖尿病患者皮下脂肪组织FAT/CD36表达分别上调+ 58%、+ 76%和+ 150%。相对于皮下脂肪组织，内脏脂肪组织FAT/CD36表达在瘦肉组（+52%）和超重组（+30%）上调。相比之下，在肥胖受试者和2型糖尿病患者中，皮下和内脏脂肪组织库的FAT/CD36蛋白表达无差异（P < 0.05）。皮下脂肪组织FAT/CD36表达（R = 0.85）和内脏脂肪组织FAT/CD36表达（R = 0.77）与BMI、循环葡萄糖和胰岛素的改变相关。结论：肥胖和2型糖尿病患者皮下脂肪组织FAT/CD36表达上调。由于FAT/CD36在瘦、超重和肥胖受试者中表达没有差异，仅在2型糖尿病患者中表达增加，因此内脏脂肪组织FAT/CD36对代谢紊乱的反应可能比皮下脂肪组织FAT/CD36更不动态。
Background: Long-chain fatty acids (LCFAs) cross the plasma membrane via a protein-mediated mechanism involving one or more LCFA-binding proteins. Among these, FAT/CD36 has been identified as key LCFA transporter in the heart and skeletal muscle, where it is regulated acutely and chronically by insulin. In skeletal muscle, FAT/CD36 expression and/or subcellular distribution is altered in obesity and type 2 diabetes. There is limited information as to whether the expression of this protein is also altered in subcutaneous and/or visceral adipose tissue depots in human obesity or type 2 diabetes.Objectives: To compare (a) the expression of FAT/CD36 in subcutaneous and visceral adipose tissue depots in lean, overweight, and obese individuals and in type 2 diabetics, (b) to determine whether the protein expression of FAT/CD36 in these depots is associated with the severity of insulin resistance (type 2 diabetes > obese > overweight/lean) and (c) whether FAT/CD36 protein expression in these adipose tissue depots is associated with alterations in circulating substrates and hormones. Subjects: Subjects who were undergoing abdominal surgery and who were lean (n = 10; three men, seven women), overweight (n = 10; three men, seven women) or obese (n = 7; one man, six women), or who had been diagnosed with type 2 diabetes (n = 5; one man, four women) participated in this study.Measurements: Subcutaneous and visceral adipose tissue samples, as well as blood samples, were obtained from the subjects while under general anesthesia. Adipose tissue samples were analyzed for FAT/CD36 using Western blotting. Serum samples were analyzed for glucose, insulin, FFA and leptin. BMI was also calculated.Results: Subcutaneous adipose tissue FAT/CD36 expression was upregulated by + 58, + 76 and + 150% in overweight, obese and type 2 diabetics, respectively. Relative to subcutaneous adipose tissue, visceral adipose tissue FAT/CD36 expression was upregulated in lean (+52%) and overweight subjects (+30%). In contrast, in obese subjects and type 2 diabetics, no difference in FAT/CD36 protein expression was observed between their subcutaneous and visceral adipose tissue depots (P > 0.05). The subcutaneous adipose tissue FAT/CD36 expression (R = 0.85) and the visceral adipose tissue FAT/CD36 expression (R = 0.77) were associated with alteration in BMI and circulating glucose and insulin.Conclusions: Subcutaneous adipose tissue FAT/CD36 expression is upregulated in obesity and type 2 diabetes. As FAT/CD36 expression is not different in lean, overweight and obese subjects, and was only increased in type 2 diabetics, it appears that visceral adipose tissue FAT/CD36 may respond in a less dynamic manner to metabolic disturbances than subcutaneous adipose tissue FAT/CD36.