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Diabetes 54:2838-2843, 2005
© 2005 by the American Diabetes Association, Inc.
Activation of the Peripheral Endocannabinoid System in Human Obesity
1 Franz Volhard Clinical Research Center, Charité Campus Buch, and HELIOS Klinikum Berlin, Berlin, Germany
2 Laboratory of Physiologic Studies, National Institute on Alcohol Abuse & Alcoholism, National Institutes of Health, Bethesda, Maryland
3 Cardiovascular Obesity Research & Management, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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.
Address correspondence and reprint requests to Stefan Engeli, MD, Franz Volhard Clinical Research Center (Haus 129), Charité Campus Buch, Wiltbergstr. 50, 13125, Berlin, Germany. E-mail: engeli{at}fvk.charite-buch.de
Abbreviations: 2-AG, 2-arachidonoylglycerol; AEA, anandamide; CB, cannabinoid; FAAH, fatty acid amide hydrolase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; SREBP-1c, sterol regulatory element–binding protein 1c
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