ObjectiveCapsaicinoids (CAPs), most commonly found in chili peppers, have a multitude of pharmacological and physiological effects, such as anti-inflammation, antioxidant, and anticancer effects. In the present study, we set out to investigate the hypothesis that CAPs mitigate obesity in rats and the possible mechanisms thereof.Materials and methodsRats were divided into six groups, including control (±10 mg CAPs/kg body weight [BW]), low-fat–high-sucrose diet (±10 mg CAPs/kg BW), and high-fat diet (±10 mg CAPs/kg BW). Blood samples and liver and aortic tissues were taken at the end of the study.ResultsCAPs supplementation significantly reduced hyperglycemia and hyperlipidemia (P<0.001) and ameliorated oxidative damage by reducing malondialdehyde concentrations in serum and liver and by increasing total antioxidant capacity in serum induced by the low-fat–high-sucrose and high-fat diets (P<0.001 for all). CAPs also depressed levels of NFκB p65, gp91phox, and p22phox, essential components of NADPH oxidase, in the aorta of rats. However, levels of Nrf2, Sirt1, and endothelial nitric oxide synthase were significantly increased in the aorta.ConclusionCAPs may at least partially reduce adverse effects due to high-fat diet and sucrose consumption through regulation of energy metabolism, oxidative stress, and proteins involved in vasoprotection.