Peripheral endocannabinoid system activity in patients treated with sibutramine.
OBJECTIVE
The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.


METHODS
Twenty obese otherwise healthy patients received randomized, double-blind, crossover treatment with placebo and 15 mg/day sibutramine for 5 days each, followed by 12 weeks open-label sibutramine treatment. We determined circulating anandamide and 2-arachidonoylglycerol and expression levels of endocannabinoid genes in subcutaneous abdominal adipose tissue biopsies.


RESULTS
Body weight was stable during the acute treatment period and decreased by 6.0+/-0.8 kg in those patients completing 3 months of sibutramine treatment (P<0.05). Circulating endocannabinoids and the expression of ECS genes did not change with acute or chronic sibutramine treatment.


CONCLUSIONS
The ECS is activated in obesity. We did not find any influence of 5% body weight loss induced by sibutramine on circulating levels of endocannabinoids and adipose-tissue expression of endocannabinoid genes in obese subjects. These data confirm our previous findings on dietary weight loss and suggest that the dysregulation of the ECS may be a cause rather than a consequence of obesity.
Engeli
Stefan
S
Franz Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany. stefan.engeli@charite.de
Heusser
Karsten
K
Janke
Jürgen
J
Gorzelniak
Kerstin
K
Bátkai
Sándor
S
Pacher
Pál
P
Harvey-White
Judith
J
Luft
Friedrich C
FC
Jordan
Jens
J
D050153:Abdominal Fat / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D001067:Appetite Depressants / Q000494:pharmacology / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000097:blood; D001706:Biopsy; D001835:Body Weight / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000235:genetics / Q000378:metabolism*; D018592:Cross-Over Studies; D003503:Cyclobutanes / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D063388:Endocannabinoids; D005786:Gene Expression Regulation; D005989:Glycerides / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D053284:Polyunsaturated Alkamides / Q000097:blood; D012044:Regression Analysis; D015431:Weight Loss / Q000502:physiology
D001067:Appetite Depressants; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D003503:Cyclobutanes; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide; C058254:sibutramine