Abstract
It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol—CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.
Highlights
IntroductionIt is known that continuous heart work is associated with increased cardiomyocytes metabolic demands and a wide range of substrates that can be utilized during ATP synthesis, e.g., fatty acids (FAs), carbohydrates (glucose and lactate), ketone bodies, and amino acids [1]
Before 2-week CBD treatment, body weight of rats after five weeks of high-fat diet course was considerably elevated in both HFD and HFD + CBD groups compared to the respective control group (+3.08% and +8.32%, p < 0.05, Figure 1A, before treatment)
Our study has shown the relationship between myocardial sphingolipid metabolism and CBD treatment in high-fat diet-induced obesity in rats
Summary
It is known that continuous heart work is associated with increased cardiomyocytes metabolic demands and a wide range of substrates that can be utilized during ATP synthesis, e.g., fatty acids (FAs), carbohydrates (glucose and lactate), ketone bodies, and amino acids [1]
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