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

Chem Phys Lipids. 2017 Apr:204:85-93. doi: 10.1016/j.chemphyslip.2017.03.009. Epub 2017 Mar 29.

Abstract

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.

Keywords: CB1 receptor blockade; Endocannabinoid system; Free fatty acid profile; Mice; NAFLD; Rimonabant.

MeSH terms

  • Administration, Oral
  • Animals
  • Cannabinoid Receptor Antagonists / administration & dosage
  • Cannabinoid Receptor Antagonists / pharmacology*
  • Diet, High-Fat
  • Fatty Acids, Nonesterified / metabolism*
  • Liver / drug effects*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • 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

Substances

  • Cannabinoid Receptor Antagonists
  • Cnr2 protein, mouse
  • Fatty Acids, Nonesterified
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB2
  • Rimonabant