The effect of cannabinoid receptor 1 blockade on adipokine and proinflammatory cytokine concentration in adipose and hepatic tissue in mice with nonalcoholic fatty liver disease

Can J Physiol Pharmacol. 2019 Feb;97(2):120-129. doi: 10.1139/cjpp-2018-0607. Epub 2019 Jan 23.

Abstract

In high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD), there is an increase in the endocannabinoid system activity, which significantly contributes to steatosis development. The aim of our study was to investigate the effects of cannabinoid receptor type 1 blockade on adipokine and proinflammatory cytokine content in adipose and hepatic tissue in mice with NAFLD. Male mice C57BL/6 were divided into a control group fed with a control diet for 20 weeks (C, n = 6) a group fed with a HFD for 20 weeks (HF, n = 6), a group fed with a control diet and treated with rimonabant after 18 weeks (R, n = 9), and a group fed with HFD and treated with rimonabant after 18 weeks (HFR, n = 10). Rimonabant significantly decreased leptin, resistin, apelin, visfatin, interleukin 6 (IL-6), and interferon-γ (IFN-γ) concentration in subcutaneous and visceral adipose tissue in the HFR group compared to the HF group (p < 0.01). Rimonabant reduced hepatic IL-6 and IFN-γ concentration as well as plasma glucose and insulin concentration and the homeostatic model assessment index in the HFR group compared to the HF group (p < 0.01). It can be concluded that the potential usefulness of CB1 blockade in the treatment of HFD-induced NAFLD is due to modulation of the adipokine profile and proinflammatory cytokines in both adipose tissues and liver as well as glucose metabolism.

Keywords: CB1 receptor blockade; NAFLD; adipokines; adipose tissue; cytokines pro-inflammatoires; endocannabinoid system; foie; inhibition des récepteurs CB1; liver; proinflammatory cytokines; stéatose hépatique non alcoolique; système endocannabinoïde; tissu adipeux.

MeSH terms

  • Adipokines / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / drug effects
  • Cannabinoid Receptor Antagonists / pharmacology*
  • Cannabinoid Receptor Antagonists / therapeutic use
  • Cytokines / metabolism*
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Glucose / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Rimonabant / pharmacology*
  • Rimonabant / therapeutic use

Substances

  • Adipokines
  • Blood Glucose
  • CNR1 protein, mouse
  • Cannabinoid Receptor Antagonists
  • Cytokines
  • Receptor, Cannabinoid, CB1
  • Glucose
  • Rimonabant