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

Area of Science:

• Biochemistry
• Metabolic Science
• Pharmacology

Background:

• Obesity is linked to harmful metabolic defects, and phytocannabinoids show potential for therapeutic intervention.
• Strategies to counteract obesity's effects using plant-derived cannabinoids are emerging.
• Understanding the impact of specific phytocannabinoids on lipid metabolism is crucial.

Purpose of the Study:

• To investigate the therapeutic effects of cannabigerol (CBG) on intramuscular fatty acids and lipid metabolism in diet-induced obesity.
• To examine CBG's impact on mitochondrial cardiolipin composition and cellular antioxidant defense.
• To elucidate the mechanisms underlying CBG's action in protecting myocytes from lipotoxicity.

Main Methods:

• Male Wistar rats were subjected to a high-fat, high-sucrose diet to induce obesity.
• Treatment involved 2-week administration of cannabigerol (CBG).
• Assessed fatty acid transporters, lipid profiles, cardiolipin content, enzyme activity (cytochrome c oxidase), and oxidative stress markers (SOD, lipid peroxides) using Western blotting, gas-liquid chromatography, and immunoenzymatic kits.

Main Results:

• CBG treatment limited fatty acid transporter recruitment, reducing intracellular fatty acid influx and lipogenesis in myocytes.
• Obesity-induced defective cardiolipin remodeling, with excess docosahexaenoic acid accumulation, was ameliorated by CBG.
• CBG upregulated muscular cardiolipin, prevented C22:6n-3 buildup, increased superoxide dismutase (SOD) levels, and reduced lipid peroxidation.

Conclusions:

• Cannabigerol (CBG) demonstrates a therapeutic potential in mitigating obesity-associated muscular metabolic defects.
• CBG limits lipotoxicity by controlling fatty acid metabolism and enhances cellular antioxidant defense.
• These findings suggest CBG as a promising candidate for targeting muscle-specific metabolic dysfunctions in obesity.