Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity

TLDR

The endocannabinoid system is suspected to link visceral fat accumulation with metabolic disease. The study aimed to assess whether circulating endocannabinoids associate with visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese individuals. Researchers measured circulating endocannabinoids and quantified CB1 and FAAH gene expression in paired subcutaneous and visceral adipose tissue samples from 60 subjects. Higher circulating 2‑AG correlated with greater body and visceral fat, higher insulin, and lower glucose infusion rates, while CB1 and FAAH expression in visceral fat inversely related to fat mass, insulin, and 2‑AG, indicating abdominal obesity drives peripheral endocannabinoid dysregulation and may be a therapeutic target.

Abstract

The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB1) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB1 mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes.