| Autor: |
Alves R; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil., Suehiro CL; Department of Pathology, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil.; Department of Internal Medicine, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil., Oliveira FG; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil., Frantz EDC; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil., Medeiros RF; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil., Vieira RP; Department of Internal Medicine, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil.; Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), Sao Jose dos Campos, Sao Paulo, Brazil.; Graduate Program in Sciences of Human Movement and Rehabilitation, Federal University of Sao Paulo, Santos, Sao Paulo, Brazil.; Graduate Program in Bioengineering, Universidade Brasil, Campus Itaquera, Sao Paulo, Sao Paulo, Brazil.; School of Medicine, Anhembi Morumbi University, São José dos Campos, Sao Paulo, Brazil., Martins MA; Department of Internal Medicine, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil., Lin CJ; Department of Pathology, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil., Nobrega ACLD; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil., Toledo-Arruda AC; Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil.; National Institute for Science and Technology-INCT (In)activity and Exercise, Conselho Nacional de Desenvolvimento Científico e Tecnológico-Niterói (RJ), Rio de Janeiro, Brazil.; Department of Pathology, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil.; Department of Internal Medicine, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil. |
| Abstrakt: |
The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECH-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-1β, IL-10, cardiac hypertrophy, and cardiac NF-κB-p65 and TNF-α expression, which were reduced by exercise ( P < 0.05). Cardiac ANG II type 1 receptor and NAD(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/Kelch-like 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. |
