Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption

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art_ALVES_Aerobic_exercise_modulates_cardiac_NADPH_oxidase_and_the_2020.PDF.pdf (2.53 MB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2020
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMER PHYSIOLOGICAL SOC
Autores
ALVES, Renata
OLIVEIRA, Flavia Garcia de
FRANTZ, Eliete Dalla Corte
MEDEIROS, Renata Frauches de
NOBREGA, Antonio Claudio Lucas da
Citação
JOURNAL OF APPLIED PHYSIOLOGY, v.128, n.1, p.59-69, 2020
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECU-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups (n = 10). After 12 wk. the energy intake and body weight in the groups were similar. Maximum exercise testing, resting energy expenditure, resting oxygen consumption, and carbon dioxide production increased in the exercise groups (Exercise and Fructose + Exercise vs. Control and Fructose groups. P < 0.05). Chronic fructose intake induced circulating hypercholesterolemia, hypertriglyceridemia. and hyperleptinemia and increased white adipose tissue depots, with no changes in blood pressure. This metabolic environment increased circulating IL-6, IL-1 beta, IL-10, cardiac hypertrophy. and cardiac NF-kappa B-p65 and TNF-alpha expression, which were reduced by exercise (P < 0.05). Cardiac ANC. II type 1 receptor and NiD(P)H oxidase 2 (NOX2) were increased by fructose intake and exercise decreased this response (P < 0.05). Exercise increased the cardiac expression of the NRF2-to-KEAP1 ratio and phase II antioxidants in fructose-fed mice (P < 0.05). NOX4, glutathione reductase, and catalase protein expression were similar between the groups. These findings suggest that exercise confers modulatory cardiac effects, improving antioxidant defenses through the NRF2/KEAP1 pathway and decreasing oxidative stress, representing a potential nonpharmacological approach to protect against fructose-induced cardiometabolic diseases. NEW & NOTEWORTHY This is the first study to evaluate the cardiac modulation of NAD(P)H oxidase (NOX), the NRF2/Kelchlike ECH-associated protein 1 pathway (KEAP), and the thioredoxin TRX1) system through exercise in the presence of moderate fructose intake. We demonstrated a novel mechanism by which exercise improves cardiac antioxidant defenses in an experimental model of chronic fructose intake, which involves NRF2-to-KEAP1 ratio modulation, enhancing the local phase II antioxidants hemoxygenase-1, thioredoxin reductase (TXNRD1), and peroxiredoxin1B (PDRX1), and inhibiting cardiac NOX2 overexpression.
Palavras-chave
antioxidants, cardiometabolic disease, exercise, fructose
URI
https://observatorio.fm.usp.br/handle/OPI/35526
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - LIM/20
Artigos e Materiais de Revistas Científicas - LIM/22
Artigos e Materiais de Revistas Científicas - ODS/03