Sodium butyrate attenuates aortic lipotoxicity and impaired nitric oxide synthesis in female Wistar rats exposed to high‑fructose drink

Abstract

High fructose (HFr) intake results in dyslipidemia with consequent insulin resistance through metabolic derangements. Inadequate mobilization of excess lipid into lipid droplets causes lipid accumulation with subsequent lipotoxicity in nonadipose tissues, thus contributing to cardiovascular disease. Short-chain fatty acid butyrate protects against cardiometabolic disorder (CMD). This study aimed at investigating the effect of sodium butyrate (NaB) on selected markers of endothelial function and aortic lipotoxicity in female Wistar rats. Twenty female Wistar rats with body weight 120–125 g were divided after a week of acclimatization into 4 groups of 5 rats each: control (CTR; normal chow), HFr drink: 10% fructose (w/v), NaB (200 mg/kg; po), and NaB + HFr. The administration was carried out for 6 weeks. The animals were euthanized with ketamine hydrochloride and blood samples were collected by cardiac puncture. Aortic tissue ring was excised and homogenized for biochemical parameters using standard assay methods. The results showed that HFr drink decreased plasma and aortic NO, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and high-density lipoprotein cholesterol (HDL), while it increased plasma and aortic triglyceride (TG), free fatty acid (FFA), uric acid (UA), and C-reactive protein (CRP) compared with the control group (p < 0.05). Interestingly, administration of NaB attenuated these metabolic-related perturbations in rats exposed to HFr. Therefore, the results of this study suggest that NaB protects against aortic lipotoxicity and endothelial dysfunction associated with HFr drink by attenuating aortic lipid deposition and improving VEGF.