Around a third of adults around the world live with metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle changes like improved diet and physical activity are typically recommended to manage the disease. Few pharmaceutical treatment options are currently available.
In recent years, CBD and CBG have arisen as potential candidates for treating MASLD due to their anti-inflammatory, antioxidant, and metabolic-modulating properties. The underlying mechanisms behind their beneficial effects, however, remain unclear.
In the current study, researchers investigated how CBD and CBG affect a mouse model of diet-induced obesity and MASLD. To do so, they fed male mice a high-fat diet for 14 weeks before daily treatment with CBD, CBG, or a vehicle for 4 weeks.
Ultimately, the researchers found that CBD and CBG improved glycaemic control, reduced hepatic triglycerides, and normalized serum lipids without affecting energy expenditure.
The compounds were found to increase levels of phosphocreatine, which acts as a backup energy supply and helps liver cells maintain normal function when exposed to metabolic stressors like a high-fat diet.
The compounds also reactivated cathepsins, enzymes that function within lysosomes and help break down unwanted materials in cells so they can be removed. Restoring cathepsin activity enabled liver cells to better process and eliminate harmful fats and waste.
Overall, CBG produced greater improvements in multiple metabolic markers, reducing body fat mass and increasing insulin sensitivity more than CBD. The compound also showed a stronger ability to lower total cholesterol and ‘bad’ LDL cholesterol.
"Our findings identify a new mechanism by which CBD and CBG enhance hepatic energy and lysosomal function. This dual metabolic remodeling contributes to improved liver lipid handling and highlights these compounds as promising therapeutic agents for MASLD,” said study author, Prof. Joseph Tam of the School of Pharmacy at The Hebrew University of Jerusalem, in a press release.
The researchers noted that further research is needed to understand how the findings translate to human treatments.
Sources: Science Daily, British Journal of Pharmacology
