Cannabis Extracts Affected Metabolic Syndrome Parameters in Mice Fed High-Fat/Cholesterol Diet.

The Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
Eastern Regional R&D Center, Kiryat Arba, Israel.
Department of Plant Pathology and Weed Research, Volcani Center, Rishon LeZion, Israel.
Sackler School of Medicine, Tel Aviv University, Timrat, Israel.
Institute of Soil, Water and Environmental Sciences, Volcani Center, Rishon LeZion, Israel.

Nonalcoholic Fatty Liver Disease -- Drug Therapy ; Medical Marijuana -- Pharmacodynamics ; Plant Extracts -- Pharmacodynamics ; Disease Progression ; Metabolic Syndrome X ; Dietary Fats

Animal Studies; Mice; Dietary Fats -- Administration and Dosage; Medical Marijuana -- Administration and Dosage; Time Factors; Lipids -- Blood; Glucose Tolerance Test; Gene Expression; Microbiota -- Drug Effects; Outcome Assessment; Descriptive Statistics

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis may potentially be beneficial for treating metabolic disorders such as NAFLD, the effects of cannabis on liver diseases and gut microbiota profile are yet to be addressed. In this study, we evaluated the therapeutic effects of cannabis strains with different cannabinoid profiles on NAFLD progression. Materials and Methods: NAFLD was induced by feeding mice a high-fat/cholesterol diet (HFCD) for 6 weeks. During this period, cannabis extracts were administrated orally at a concentration of 5 mg/kg every 3 days. Profile of lipids, liver enzymes, glucose tolerance, and gene expression related to carbohydrate lipid metabolism and liver inflammation were analyzed. The effect of cannabis strains on microbiota composition in the gut was evaluated. Results: A cannabidiol (CBD)-rich extract produced an increase in inflammatory related gene expression and a less diverse microbiota profile, associated with increased fasting glucose levels in HFCD-fed mice. In contrast, mice receiving a tetrahydrocannabinol (THC)-rich extract exhibited moderate weight gain, improved glucose response curves, and a decrease in liver enzymes. Conclusions: The results of this study indicate that the administration of cannabis containing elevated levels of THC may help ameliorate symptoms of NAFLD, whereas administration of CBD-rich cannabis extracts may cause a proinflammatory effect in the liver, linked with an unfavorable change in the microbiota profile. Our preliminary data suggest that these effects are mediated by mechanisms other than increased expression of the endocannabinoid receptors cannabinoid receptor 1 (CB1) and CB2.

2378-8763

20200929

20200929

10.1089/can.2020.0013

145623021