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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...

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Autores principales: Najjar, Rami, Meister, Maureen, Knapp, Denise, Wanders, Desiree, Feresin, Rafaela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193787/
http://dx.doi.org/10.1093/cdn/nzac053.062
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author Najjar, Rami
Meister, Maureen
Knapp, Denise
Wanders, Desiree
Feresin, Rafaela
author_facet Najjar, Rami
Meister, Maureen
Knapp, Denise
Wanders, Desiree
Feresin, Rafaela
author_sort Najjar, Rami
collection PubMed
description 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.
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spelling pubmed-91937872022-06-14 Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2 Najjar, Rami Meister, Maureen Knapp, Denise Wanders, Desiree Feresin, Rafaela Curr Dev Nutr Dietary Bioactive Components 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. Oxford University Press 2022-06-14 /pmc/articles/PMC9193787/ http://dx.doi.org/10.1093/cdn/nzac053.062 Text en © The Author 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Dietary Bioactive Components
Najjar, Rami
Meister, Maureen
Knapp, Denise
Wanders, Desiree
Feresin, Rafaela
Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title_full Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title_fullStr Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title_full_unstemmed Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title_short Raspberry Protects Against High-Fat, High-Sucrose Diet-Induced Vascular Oxidative Stress via NRF2
title_sort raspberry protects against high-fat, high-sucrose diet-induced vascular oxidative stress via nrf2
topic Dietary Bioactive Components
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9193787/
http://dx.doi.org/10.1093/cdn/nzac053.062
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