Cannabidiol and Indole-3-carbinol Reduce Intracellular Lipid Droplet Accumulation in HepaRG, A Human Liver Cell Line, as well as in Human Adipocytes

Introduction: An increase in obesity-related diseases is becoming an alarming worldwide problem. Therefore, new therapeutic methods are constantly sought to prevent, treat, and alleviate symptoms of the diseases associated with obesity. Method: This study investigates the effects of two natural compounds (indole-3-carbinol, I3C, a bioactive indolic compound found in cruciferous vegetables; cannabidiol, CBD, the active ingredient derived from the hemp plant) on the fatty acid accumulation in the human liver cell line HepaRG, a well-established model for non-alcoholic fatty liver disease (NAFLD) and in human pre-adipocytes (adipose-derived mesenchymal stem cells, MSC). Results: EC50s of each compound were in the high μM range (approximately 30 mg/L), showing the low toxicity of these compounds. Determination of the selected compounds in cell media showed no significant differences during the exposure, suggesting that no significant metabolism or degradation happened during the exposure time. Quantification of the bioaccumulation of lipid droplets on exposed HepaRG revealed a significant reduction and mitigation of fatty acid accumulation when exposed to 1 nM of I3C and 100 nM of CBD.). On MSC cells a significant inhibition of lipogenesis and adipocyte differentiation was observed in cells exposed to 0.1 nM of I3C and 1 nM of CBD. Conclusion: This study provides a significant contribution to advancing the understanding of preventative dietary strategies that target adipocyte differentiation and NAFLD.