Immune-mediated activation of the endocannabinoid system in visceral adipose tissue in obesity.
The aim of the study was to investigate if the endocannabinoid system (ECS) is activated in visceral adipose tissue and if adipose tissue inflammation affects the ECS activation state. Therefore, expression of fatty acid amide hydrolase (FAAH), cannabinoid receptor 1 (Cb1), adiponectin, and tumor necrosis factor (TNF)-alpha was compared in visceral adipose tissue from 10 normal-weight (BMI 24.4+/-1.1 kg/m2) and 11 obese subjects (BMI 37.6+/-13.6 kg/m2) using quantitative RT-PCR, and gene expression changes were analyzed after in vitro stimulation of visceral adipose tissue with TNF-alpha. The data demonstrate that the ECS is activated in obese visceral adipose tissue as shown by decreased FAAH, Cb1, and adiponectin expression. Obesity-related ECS activation is accompanied by elevated expression of the pro-inflammatory cytokine TNF-alpha, which in turn stimulates ECS activation in vitro. Our data show a strong association between adipose tissue inflammation and ECS activation in obesity, and indicate that a pro-inflammatory state may directly activate the ECS.
Kempf
K
K
Institute for Clinical Diabetes Research, German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Düsseldorf, Germany. Kerstin.Kempf@ddz.uni-duesseldorf.de
Hector
J
J
Strate
T
T
Schwarzloh
B
B
Rose
B
B
Herder
C
C
Martin
S
S
Algenstaedt
P
P
D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D063388:Endocannabinoids; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000099252:Fatty Acid Amide Hydrolases
D052242:Adiponectin; D000581:Amidohydrolases; D063385:Cannabinoid Receptor Modulators; D016207:Cytokines; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D014409:Tumor Necrosis Factor-alpha; D000099252:Fatty Acid Amide Hydrolases; C499918:ADIPOQ protein, human