Early cardiac lipid overload, redox-inflammatory imbalance, fibrotic remodeling, and cannabinoid receptor up-regulation in sucrose-rich diet-fed rats: preventive effects of full-spectrum cannabis oil

Introduction Excessive intake of added sugars promotes metabolic disease, but the earliest myocardial responses to sugar-driven metabolic overload and their modulation by plant-derived bioactive compounds remain incompletely understood. We investigated whether a short-term sucrose-rich diet induces early cardiac remodeling and whether a full-spectrum cannabis oil (CO) can prevent these alterations. Methods Male Wistar rats were assigned for 3 weeks to a reference diet, a sucrose-rich diet, or a sucrose-rich diet plus full-spectrum CO (cannabidiol [CBD]: tetrahydrocannabinol [THC] ratio 2:1; 1 mg/kg/day, orally). Results Throughout the study period, the sucrose-rich diet significantly increased systolic and diastolic blood pressure (group effect, p = 0.0003 and p = 0.0029, respectively) and circulating cardiac injury markers (creatine kinase-MB [CK-MB], p = 0.0048; lactate dehydrogenase [LDH], p = 0.0173), promoted myocardial triglyceride accumulation ( p = 0.0002), and altered lipid metabolism-related regulators (e.g., fatty acid synthase [FAS], p = 0.0002; sterol regulatory element-binding protein 1c [SREBP-1c], p = 0.0007). These changes were accompanied by oxidative stress (reactive oxygen species [ROS], p < 0.0001), impaired antioxidant defenses (catalase [CAT], p < 0.0001), inflammatory and endothelial activation (nuclear factor-κB [NF-κB], p = 0.0049; vascular cell adhesion molecule-1 [VCAM-1], p < 0.0001), early fibrotic remodeling (myocardial collagen content, p < 0.0001), histological and ultrastructural injury, and increased cardiac cannabinoid receptor type 1 (CB 1 R, p = 0.0001) and cannabinoid receptor type 2 (CB 2 R, p = 0.0003) protein expression, whereas electrocardiographic parameters (heart rate, PR interval, QRS complex, corrected QT interval [QTc]) remained unchanged (all p > 0.05). Discussion Cannabis oil administration prevented or markedly attenuated most of these alterations, including cardiac lipid accumulation, redox imbalance, inflammatory and remodeling-related signaling, structural damage, and cannabinoid receptor upregulation. These findings show that the myocardium is an early target of sucrose-driven metabolic overload and identify full-spectrum CO as a plant-derived bioactive intervention capable of limiting early cardiac metabolic and redox-inflammatory remodeling in this preclinical model. Further studies are required to define the contribution of individual phytocannabinoids and to determine whether cannabinoid receptor signaling contributes to these effects.