Abstract Background and Objectives: Obesity has been reported to be associated with vascular dysfunction and morphology changes. This study aimed to evaluate the effect of limonin on vascular function and morphology in high fat (HF) diet-induced obesity in rats. Methods: Male Sprague-Dawley rats were divided into 3 groups; control group fed with normal diet and tap water; obese group fed with a HF-diet together with 15% fructose solution for 16 weeks and obese+LM100 group fed with a HF-diet plus 15% fructose solution, and limonin (100 mg/kg) for the last 4 weeks. At the end of the study, body weight (BW), retroperitoneal fat weight (RFW), vascular function, vascular morphology and oxidative stress markers were determined. Results: Obese rats had increases in BW and RFW while treatment with limonin can attenuate the high BW and RFW (p<0.05). Limonin improved vascular function by reducing the enhancement of contractile response to electrical filed stimulation in the mesenteric vascular beds and attenuated the impairment of vasorelaxation response to acetylcholine in aortic rings isolated from obese rats (p<0.05). Aortic hypertrophy, indicated by increases in cross-sectional area, aortic wall thickness and wall/lumen ratio, was normalized in obese rats after limonin treatment. Moreover, increased vascular superoxide production, and decreased plasma nitric oxide metabolites were also observed in obese rats and these were restored by limonin treatment (p<0.05). Conclusion: Limonin alleviated vascular dysfunction and hypertrophy in obese rats. The possible mechanism might associate with its anti-obesity and antioxidant properties.
