Activation of the Peripheral Endocannabinoid System in Human Obesity

TLDR

Obesity is a major risk factor for type 2 diabetes, and activation of the central endocannabinoid system promotes weight gain, while CB‑1 blockade reduces body weight. The study aims to investigate the role of the peripheral endocannabinoid system in human obesity. We measured circulating endocannabinoid concentrations and assessed CB‑1 and FAAH expression in adipose tissue of lean and obese women, and in a separate group after a 5 % weight loss. Obese women exhibited 35 %–52 % higher circulating anandamide and 2‑AG, 34 %–59 % lower adipose CB‑1 and FAAH mRNA, a strong inverse correlation between FAAH and endocannabinoids, and no change after weight loss, confirming an up‑regulated peripheral endocannabinoid system in obesity.

Abstract

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.