Activation of the peripheral endocannabinoid system in human obesity.
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.
Engeli
Stefan
S
Franz Volhard Clinical Research Center, Charité Campus Buch, 13125 Berlin, Germany. engeli@fvk.charite-buch.de
Böhnke
Jana
J
Feldpausch
Mareike
M
Gorzelniak
Kerstin
K
Janke
Jürgen
J
Bátkai
Sándor
S
Pacher
Pál
P
Harvey-White
Judy
J
Luft
Friedrich C
FC
Sharma
Arya M
AM
Jordan
Jens
J
D000273:Adipose Tissue / Q000737:chemistry; D000581:Amidohydrolases / Q000235:genetics; D001095:Arachidonic Acids / Q000097:blood; D001823:Body Composition; D015992:Body Mass Index; D063385:Cannabinoid Receptor Modulators / Q000097:blood / Q000502:physiology*; D063388:Endocannabinoids; D005260:Female; D015870:Gene Expression; D005989:Glycerides / Q000097:blood; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D017698:Postmenopause; D012333:RNA, Messenger / Q000032:analysis; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015431:Weight Loss; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C094503:glyceryl 2-arachidonate; C078814:anandamide