Cannabigerol Alleviates Obesity-Induced Mitochondrial Dysfunction by Cardiolipin Fatty Acid Remodeling.

Abstract

<p>Until now, strategies to offset the harmful effects of obesity using phytocannabinoids have only begun to be unraveled. Therefore, we aimed to identify the possible therapeutic role of 2-week cannabigerol (CBG) treatment on intramuscular fatty acids (FAs) and lipid metabolism, with subsequent implications for mitochondrial cardiolipin composition in male Wistar rats in the context of a high-fat, high-sucrose diet-induced obesity. To elucidate underlying mechanisms, we assessed expression and cellular localization of fatty acid-handling proteins, intramuscular lipid profile, the total expression of proteins involved in FAs synthesis and metabolism, cardiolipin content and composition, cytochrome c oxidase activity, as well as superoxide dismutase (SOD) level and lipid peroxides formation using Western blotting, gas-liquid chromatography, and immunoenzymatic kits. Our findings demonstrate that CBG alleviates obesity-induced recruitment of fatty acid transporters to the plasma membrane, thereby limiting intracellular FAs influx and protecting myocytes against excess lipogenesis and subsequent lipid storage. Moreover, we also revealed obesity-related defective cardiolipin fatty-acyl chain remodeling, characterized by excess accumulation of docosahexaenoic acid, leading to increased unsaturated aldehyde formation. Importantly, CBG upregulated muscular cardiolipin and prevented the buildup of C22:6n-3, which was accompanied by elevated SOD levels and reduced formation of lipid peroxidation products, indicating enhanced cellular antioxidant defense. Hence, CBG-mediated effects may fulfill an urgent, so far unmet clinical need for treatments that can directly target muscular obesity-associated metabolic defects.</p>