Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity.
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 (CB(1)) 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, CB(1) 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.
Blüher
Matthias
M
University of Leipzig, Medical Department III, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Engeli
Stefan
S
Klöting
Nora
N
Berndt
Janin
J
Fasshauer
Mathias
M
Bátkai
Sándor
S
Pacher
Pál
P
Schön
Michael R
MR
Jordan
Jens
J
Stumvoll
Michael
M
D000005:Abdomen; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000503:physiopathology*; D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D001095:Arachidonic Acids / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D001835:Body Weight; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D063388:Endocannabinoids; D005260:Female; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D005989:Glycerides / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D012727:Sex Characteristics; D013851:Thinness; D014781:Viscera / Q000033:anatomy & histology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D001786:Blood Glucose; D063385:Cannabinoid Receptor Modulators; D002784:Cholesterol; D063388:Endocannabinoids; D005989:Glycerides; D007328:Insulin; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate