title: Peripheral endocannabinoid system activity in patients treated with sibutramine.
abstract: 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.
authors: Franz Volhard Clinical Research Center, Medical Faculty of the Charité and HELIOS Klinikum, Berlin, Germany. stefan.engeli@charite.de
authors: Stefan
authors: S
authors: Engeli
authors: Karsten
authors: K
authors: Heusser
authors: Jürgen
authors: J
authors: Janke
authors: Kerstin
authors: K
authors: Gorzelniak
authors: Sándor
authors: S
authors: Bátkai
authors: Pál
authors: P
authors: Pacher
authors: Judith
authors: J
authors: Harvey-White
authors: Friedrich C
authors: FC
authors: Luft
authors: Jens
authors: J
authors: Jordan
mesh_terms: 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
chemical_list: 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