Cannabinoid Modulation of Metabolic Dysfunction Associated Steatotic Liver Disease in a Mouse Model

The liver plays an essential role in regulating metabolism. Though, when the physiology of the liver is thrown off, this can lead to pathological states. Metabolic dysfunction associated steatotic liver disease (MASLD) can be a consequence of irregular physiological state in relation to metabolism. MASLD is the leading chronic liver disease globally with estimated 30% of patients affected, and incidence rates expected to rise. MASLD is diagnosed when there is a >5% build up of lipids in the hepatocytes and is not associated with high alcohol consumption. There are many risk factors associated with MASLD, such as high fat or high carbohydrate diet, sedentary lifestyle, genetic predisposition, obesity, and insulin resistance. Patients diagnosed with MASLD can reverse their fatty liver through lifestyle changes, though this may not be sustainable or practical, therefore, finding a drug treatment to alleviate MASLD is crucial. MASLD is a multifactorial disease, meaning that finding an alleviating treatment must consider multiple lenses to respect the etiological nature of this disease. Cannabinoids come from Cannabis sativa and have increasing popularity from a pharmaceutical lens. Two major cannabinoids that are non-psychoactive include cannabigerol (CBG) and cannabidiol (CBD). Previous research has shown that both CBD and CBG have anti-inflammatory and anti-oxidant effects in various diseases, though there is less research in regards to CBG. This study revealed decreased steatosis with both CBD and CBG treatment in a mice model. Further molecular studies such as the role of de novo lipogenesis, peroxisome proliferator activated receptors, and oxidative stress were evaluated to explain these findings. In response to the growing burden of MASLD, this study seeked to elucidate the molecular mechanisms underlying MASLD pathological state, with the efforts of identifying potential therapeutic strategies.