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Cannabigerol Alleviates Obesity-Induced Mitochondrial Dysfunction by Cardiolipin Fatty Acid Remodeling
Patrycja Bielawiec1, Karolina Konstantynowicz-Nowicka1, Adrian Chabowski1
1Department of Physiology, Medical University of Bialystok, Bialystok, Poland.
Abstract:
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.
Insights
Cannabigerol (CBG) treatment may combat obesity by limiting fatty acid uptake in muscles. This phytocannabinoid enhances antioxidant defense and improves mitochondrial health, offering a potential treatment for metabolic defects.
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.
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