Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2

OBJECTIVES: Elevated free fatty acids in obesity and high-fat diets can negatively impact artery function, increasing the risk of cardiovascular diseases. Raspberries (RB) are a concentrated source of polyphenols which can mediate cellular pathways in a protective manner. Thus, the objective of this study was to examine whether RB consumption could mitigate the detrimental effects of a high-fat high-sucrose (HFHS) diet in the aorta of mice in vivo and human aortic endothelial cells (HAECs) in vitro. METHODS: Eight-week-old male C57BL/6 mice were fed an AIN-93M control diet with or without 10% w/w freeze-dried RB supplementation for 4 weeks. At week 4, animals were randomized into three groups: control, HFHS, or RB + HFHS. After 24 weeks of dietary treatment, mice were sacrificed and aortas dissected for immunohistochemistry analysis. HAECs were cultured in endothelial cell growth medium and treated with 200 μg/ml of RB extract in starvation medium. After 2 h, cells were treated with 100 μM of palmitic acid (PA) for 6 h. Cells were then collected for protein expression analysis via western blot. Data were normalized to control. Statistical analysis was conducted with ANOVA followed by Dunnett's multiple comparisons test. RESULTS: In aorta, nitrotyrosine was increased in the HFHS group compared with control and RB + HFHS group. Additionally, inducible nitric oxide synthase was increased in both HFHS and RB + HFHS compared to control, but expression was not different between HFHS groups. In HAECs, PA alone had no effect on phosphorylation of endothelial nitric oxide synthase (p-eNOS(Ser1177)) compared to control. However, p-eNOS(Ser1177) expression was significantly increased in RB + PA -treated cells compared to both control and PA alone. Nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase (HO)-1 expression was also significantly increased with RB + PA treatment compared to control and PA alone. CONCLUSIONS: Raspberry consumption may reduce vascular oxidative stress induced by a HFHS diet via reduced NO oxidation despite increased iNOS in vivo. Further in vivo investigation is needed to confirm whether these effects are mediated by increased NRF2 activity. FUNDING SOURCES: Lewis College Foundation and Agriculture and Food Research Initiative (grant no. 2019–67,017-29,257/project accession no. 1,018,642) from the USDA National Institute of Food and Agriculture.