title: Fatty acid flux and oxidation are increased by rimonabant in obese women.
abstract: This study aimed to determine in obese women if endocannabinoid receptor antagonism has effects on fatty acid and triglyceride metabolism and insulin sensitivity which are independent from the metabolic effects of weight loss. Fourteen obese (BMI=33.0±0.5 kg/m(2)) (mean±SEM) Caucasian post-menopausal women, aged 57.8±4.7 years were studied. The women were randomised to 2 groups, one group received the endocannabinoid receptor antagonist rimonabant (20 mg/d) for 12 weeks. A control group achieved the same weight loss by a hypocaloric dietary intervention over 12 weeks. Palmitate production rate (Ra), a measure of lipolysis, and palmitate oxidation rate, and VLDL(1) and VLDL(2) triglyceride (TG) kinetics, were measured using isotopic tracers before and after the intervention. Weight loss was not different in the 2 groups; 2.6±0.5 kg with rimonabant and 3.1±1.0 kg in the control group. Palmitate Ra increased with rimonabant with no change in the control group (p=0.03 between groups). Palmitate oxidation rate increased with rimonabant but decreased in the control group (p=0.005 between groups). VLDL(1) TG secretion rate decreased in the control group and increased in the rimonabant group (p=0.008 between groups). There was no significant effect on insulin sensitivity. This study suggests that endocannabinoid receptor antagonism for 12 weeks in obese women increased lipolysis and fatty acid oxidation. The increase in VLDL(1) TG secretion rate may be due to the increase in lipolysis which exceeded the increase in fatty acid oxidation.
authors.affiliation: Diabetes and Metabolic Medicine, Postgraduate Medical School, University of Surrey, Guildford, UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Backhouse
authors.forename: Ivana
authors.initials: I
authors.lastname: Sarac
authors.forename: Fariba
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: Michael
authors.initials: M
authors.lastname: Stolinski
authors.forename: M Denise
authors.initials: MD
authors.lastname: Robertson
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
authors.forename: E Louise
authors.initials: EL
authors.lastname: Thomas
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: David
authors.initials: D
authors.lastname: Russell-Jones
authors.forename: A Margot
authors.initials: AM
authors.lastname: Umpleby
mesh_terms: D052242:Adiponectin / Q000097:blood; D000368:Aged; D001944:Breath Tests; D063387:Cannabinoid Receptor Antagonists; D002784:Cholesterol / Q000097:blood; D004038:Diet, Reducing; D002149:Energy Intake; D004734:Energy Metabolism / Q000187:drug effects*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010169:Palmitic Acids / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D000077285:Rimonabant; D014280:Triglycerides / Q000378:metabolism*; D006113:United Kingdom; D015431:Weight Loss
chemical_list: D052242:Adiponectin; D063387:Cannabinoid Receptor Antagonists; D005227:Fatty Acids; D020738:Leptin; D008079:Lipoproteins, VLDL; D010169:Palmitic Acids; D010880:Piperidines; D011720:Pyrazoles; D014280:Triglycerides; D002784:Cholesterol; D000077285:Rimonabant