The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease

• Published in: Chemistry and physics of lipids Vol. 204; pp. 85 - 93
• Main Authors: Jorgačević, Bojan, Vučević, Danijela, Đuričić, Ivana, Šobajić, Slađana, Mladenović, Dušan, Vesković, Milena, Vukićević, Rada Ješić, Radosavljević, Tatjana
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2017
• Subjects: Administration, Oral; Animals; Cannabinoid Receptor Antagonists - administration & dosage; Cannabinoid Receptor Antagonists - pharmacology; CB1 receptor blockade; Diet, High-Fat; Endocannabinoid system; Fatty Acids, Nonesterified - metabolism; Free fatty acid profile; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; NAFLD; Non-alcoholic Fatty Liver Disease - chemically induced; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Piperidines - administration & dosage; Piperidines - pharmacology; Pyrazoles - administration & dosage; Pyrazoles - pharmacology; Receptor, Cannabinoid, CB2 - antagonists & inhibitors; Receptor, Cannabinoid, CB2 - metabolism; Rimonabant; NAFLD; Endocannabinoid system; Mice; Rimonabant; CB1 receptor blockade; Free fatty acid profile
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2017.03.009

•Rimonabant improves hepatic fatty acid profile in nonalcoholic fatty liver disease.•Potential usefulness of CB1 blockade through modulation of plasma lipid profile.•Improvement of liver histology after treatment with CB1 blockator. We used rimonabant to investigate the role of CB1 receptor on hepatic FFAs profile during NAFLD. Male mice C57BL/6 were divided into: control group fed with control diet 20 weeks (C; n=6); group fed with HFD 20 weeks (HF; n=6); group fed with control diet and treated with rimonabant after 18 weeks (R; n=9); group fed with HFD and treated with rimonabant after 18 weeks (HFR; n=10). Rimonabant (10mg/kg) was administered daily to HFR and R group by oral gavage. Rimonabant decreased liver palmitic acid proportion in HFR group compared to HF group (p<0.05). Liver stearic and oleic acid proportions were decreased in R group compared to control (p<0.01 respectively). Rimonabant increased liver linoleic and arachidonic acid proportions in HFR group compared to HF group (p<0.01 respectively). CB1 blockade may be useful in the treatment of HFD-induced NAFLD due to modulation of plasma lipid and hepatic FFA profile.