Controversies surrounding peripheral cannabinoid receptor 1 in fatty liver disease

Context. Polycystic ovary syndrome (PCOS) is frequently associated with nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1) may be responsible for individual susceptibility to obesity and related conditions.Objective. To determine the role of genetic variants ofCNR1in the etiopathology of NAFLD in women with PCOS.Design and Setting. Our department (a tertiary referral center) conducted a cross-sectional, case-controlled study.Subjects. 173 women with PCOS (aged 20–35) and 125 healthy, age- and weight-matched controls were studied.Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms ofCNR1(rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were genotyped.Results. Frequency of the G allele of rs806381 (P<0.025) and the GG genotype of rs10485170 (P<0.03) was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly,P=0.059). In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype.Conclusion. Our preliminary results suggest the potential role ofCNR1polymorphisms in the etiology of NAFLD, especially in PCOS women.

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The role of cannabinoid receptor 1 in the development of oxidative/nitrosative stress in mice with non-alcoholic fatty liver disease

Medicinski podmladak ◽

10.5937/mp70-17890 ◽

2019 ◽

Vol 70 (1) ◽

pp. 1-8

Author(s):

Dušan Brkić ◽

Bojan Jorgačević

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Nitrosative Stress ◽

Cannabinoid Receptor ◽

Cannabinoid Receptor 1 ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0607 ◽

2019 ◽

Vol 97 (2) ◽

pp. 120-129 ◽

Cited By ~ 3

Author(s):

Bojan Jorgačević ◽

Danijela Vučević ◽

Milena Vesković ◽

Dušan Mladenović ◽

Dušan Vukićević ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Proinflammatory Cytokine ◽

Fatty Liver Disease ◽

Cannabinoid Receptor ◽

Control Diet ◽

Hepatic Tissue ◽

Nonalcoholic Fatty Liver ◽

Ifn Γ

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.

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Rimonabant Improves Oxidative/Nitrosative Stress in Mice with Nonalcoholic Fatty Liver Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/842108 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Bojan Jorgačević ◽

Dušan Mladenović ◽

Milica Ninković ◽

Milena Vesković ◽

Vesna Dragutinović ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Nitrosative Stress ◽

Cannabinoid Receptor ◽

Control Diet ◽

Control Group ◽

Standard Diet ◽

Nonalcoholic Fatty Liver

The present study deals with the effects of rimonabant on oxidative/nitrosative stress in high diet- (HFD-) induced experimental nonalcoholic fatty liver disease (NAFLD). Male mice C57BL/6 were divided into the following groups: control group fed with control diet for 20 weeks (C;n=6); group fed with HFD for 20 weeks (HF;n=6); group fed with standard 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). Daily dose of rimonabant (10 mg/kg) was administered to HFR and R group by oral gavage for two weeks. Treatment induced a decrease in hepatic malondialdehyde concentration in HFR group compared to HF group(P<0.01). The concentration of nitrites + nitrates in liver was decreased in HFR group compared to HF group(P<0.01). Liver content of reduced glutathione was higher in HFR group compared to HF group(P<0.01). Total liver superoxide dismutase activity in HFR group was decreased in comparison with HF group(P<0.01). It was found that rimonabant may influence hepatic iron, zinc, copper, and manganese status. Our study indicates potential usefulness of cannabinoid receptor type 1 blockade in the treatment of HFD-induced NAFLD.

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