Activation of the peripheral endocannabinoid system in human obesity
Activation of the peripheral endocannabinoid system in human obesity
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DOI：
10.2337/diabetes.54.10.2838
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发表时间：
2005-10-01
期刊：
影响因子：
7.7
通讯作者：
Jordan, J
中科院分区：
文献类型：
--
作者：
Engeli, S;Böhnke, J;Jordan, J
肥胖是2型糖尿病的主要危险因素。中枢内源性大麻素系统的激活会增加食物摄入量，促进体重增加。阻断大麻素1型（CB-1）受体通过中枢和外周作用减轻动物体重；外周内源性大麻素系统在人类肥胖中的作用正在被广泛研究。我们测量了循环内源性大麻素浓度，并研究了CB-1和主要降解酶脂肪酸酰胺水解酶（FAAH）在瘦肉女性（n = 20）和肥胖女性（n = 20）脂肪组织中的表达，以及在第二组女性（n = 17）体重减轻5%后的表达。肥胖女性循环中anandamide和1/2-花生四烯醇甘油水平分别比瘦子女性高35%和52% （P < 0.05）。肥胖受试者脂肪组织中CB-1 mRNA水平降低34%，FAAH mRNA水平降低59% （P < 0.05）。脂肪组织中FAAH的表达与循环内源性大麻素呈显著负相关。体重减轻5%不影响循环内源性大麻素和CB-1或FAAH的表达。与前脂肪细胞相比，CB-1和FAAH在成熟脂肪细胞中的表达增加，并且在几种人体组织中发现。我们的研究结果支持外周内源性大麻素系统的存在，该系统在人类肥胖中上调。
Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity.