Time course of neuroimmune changes induced by chronic fructose consumption in normotensive and hypertensive rats: role of aerobic exercise training

• Grant number: 15/11223-6
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2015 - February 28, 2018
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Kátia de Angelis Lobo D Avila
• Grantee: Kátia de Angelis Lobo D Avila
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The prevalence of metabolic syndrome have increased worldwide. Similarly fructose consumption is increasing due to the industrialized products like fast food and sugary drinks derived from corn syrup. It is known that increased consumption of fructose cause cardiometabolic disorders such as insulin resistance, elevated triglyceride levels, dyslipidemia, obesity and hypertension. In addition, the sympathetic hyperactivity, inflammation and oxidative stress have been identified as important mechanisms in the development of cardiometabolic diseases. Thus the present study aims to assess the time course of cardiometabolic, cardiovascular autonomic modulation, inflammatory, hormonal and oxidative stress alterations resulting from fructose overload in normotensive rats (Wistar) and spontaneously hypertensive rats (SHR). Additionally, considering the benefits obtained from regular physical activity, we aimed to evaluate the time course of the possible effects of an aerobic exercise training protocol in this condition. In this sense, we divided this project into four subprojects. We aim at subproject 1 to evaluate the time course of the changes induced by fructose overload initiated immediately after weaning (30 days old) to adulthood (90 days old) in male Wistar rats were divided into control group (C) and treated with fructose (F). In subproject 2, we have to evaluate the effects of aerobic exercise training of moderate intensity in the time course of the changes induced by the overload of fructose in Wistar rats, divided into sedentary (F) and trained (FT) treated with fructose groups. In addition, considering that fructose consumption does not induce an established hypertension condition, which is a common risk factor in the obese population with metabolic syndrome, the subproject 3 intend to evaluate the time course of the changes induced by fructose overload started soon after weaning until adulthood in rats SHR males, divided into control (C), hypertensive (H) and hypertensive patients treated with fructose (HF) groups. Finally, in the subproject 4 we intend to evaluate the effects of aerobic exercise training of moderate intensity in the time course of the changes induced by the overload of fructose in SHR rats divided into sedentary (HF) and trained (HFT) hypertensive treated with fructose groups. The above experimental groups will be divided in subgroups (n = 6 in each group / time) that will be assessed at 7, 14, 30 and 60 days of overload fructose (100 g / l in drinking water) in relation to hemodynamic parameters(blood pressure and heart rate); metabolic parameters (body weight, glucose, insulin, blood triglycerides and insulin resistance); functional capacity (maximal exercise test); autonomic parameters (baroreflex sensitivity, heart rate variability and blood pressure and catecholamines in the adipose tissue and spleen); oxidative stress parameters (lipid peroxidation of membrane protein carbonyls, activity of enzymes glutathione peroxidase, superoxide dismutase and catalase, redox balance (GSH / GSSG), total antioxidant capacity, NADPH and production of superoxide anion in the heart, pancreas, spleen and blood); nitric oxide metabolism (plasma concentration of nitrites and nitrates); inflammatory and hormonal parameters (angiotensin 2 and 1-7, AT1a receptor and the AT2 But NFkB in the heart, spleen and adipose tissue, and IL-6, IL-10 and TNF ± heart, spleen, adipose tissue). This study will test the hypothesis that changes in autonomic control precede cardiometabolic changes in normotensive and hypertensive rats treated with fructose, and that aerobic exercise training can have a preventive effect to mitigate the autonomic changes. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SARTORI, MICHELLE; CONTI, FILIPE F.; DIAS, DANIELLE DA SILVA; DOS SANTOS, FERNANDO; MACHI, JACQUELINE F.; PALOMINO, ZAIRA; CASARINI, DULCE E.; RODRIGUES, BRUNO; DE ANGELIS, KYTIA; IRIGOYEN, MARIA-CLAUDIA. Association between Diastolic Dysfunction with Inflammation and Oxidative Stress in Females ob/ob Mice. FRONTIERS IN PHYSIOLOGY, v. 8, AUG 23 2017. (10/17188-4, 15/11223-6, 11/15828-9)

FARAH, DANIELA; NUNES, JONAS; SARTORI, MICHELLE; DIAS, DANIELLE DA SILVA; SIRVENTE, RAQUEL; SILVA, MAIKON B.; FIORINO, PATRICIA; MORRIS, MARIANA; LLESUY, SUSANA; FARAH, VERA; et al. Exercise Training Prevents Cardiovascular Derangements Induced by Fructose Overload in Developing Rats. PLoS One, v. 11, n. 12, DEC 8 2016. (12/01873-5, 15/11223-6)

DIAS, DANIELLE DA SILVA; BERNARDES, NATHALIA; STOYELL-CONTI, FILIPE FERNANDES; DOS SANTOS, CAMILA PAIXAO; DE ARAUJO, AMANDA APARECIDA; LLESUY, SUSANA; INGOYEN, MARIA CLAUDIA; DE ANGELIS, KATIE. Impact of combined exercise training on the development of cardiometabolic and neuroimmune complications induced by fructose consumption in hypertensive rats. PLoS One, v. 15, n. 6, JUN 10 2020. (15/11223-6)

BERNARDES, NATHALIA; DIAS, DANIELLE DA SILVA; STOYELL-CONTI, FILIPE FERNANDES; BRITO-MONZANI, JANAINA DE OLIVEIRA; MALFITANO, CHRISTIANE; CALDINI, ELIA GARCIA; ULLOA, LUIS; LLESUY, SUSANA FRANCISCA; IRIGOYEN, MARIA-CLAUDIA; DE ANGELIS, KATIA. Baroreflex Impairment Precedes Cardiometabolic Dysfunction in an Experimental Model of Metabolic Syndrome: Role of Inflammation and Oxidative Stress. SCIENTIFIC REPORTS, v. 8, JUN 5 2018. (15/11223-6)

BRITO-MONZANI, JANAINA DE O.; SANCHES, IRIS CALLADO; BERNARDES, NATHALIA; PONCIANO, KATIA; MORAES-SILVA, IVANA C.; IRIGOYEN, MARIA-CLAUDIA; LLESUY, SUSANA; DE ANGELIS, KATIA. Hypertension induces additional cardiometabolic impairments and attenuates aerobic exercise training adaptations in fructose-fed ovariectomized rats. HYPERTENSION RESEARCH, v. 41, n. 2, p. 88-95, FEB 2018. (12/20141-5, 10/17188-4, 15/11223-6)

CONTI, FILIPE FERNANDES; IRIGOYEN, MARIA-CLAUDIA; SARTORI, MICHELLE; RIBEIRO, AMANDA APARECIDA; DOS SANTOS, FERNANDO; MACHI, JACQUELINE FREIRE; TABOAS FIGUEROA, DIEGO MENDROT; RODRIGUES, BRUNO; DE ANGELIS, KATIA. Aerobic Training Is Better Than Resistance Training on Cardiac Function and Autonomic Modulation in Female ob/ob Mice. FRONTIERS IN PHYSIOLOGY, v. 10, DEC 5 2019. (18/17183-4, 10/17188-4, 18/19006-2, 15/11223-6, 11/15828-9)

DIAS, DANIELLE DA SILVA; MORAES-SILVA, IVANA C.; BERNARDES, NATHALIA; BRITO-MONZANI, JANAINA DE OLIVEIRA; STOYELL-CONTI, FILIPE FERNANDES; MACHI, JACQUELINE FREIRE; LLESUY, SUSANA; IRIGOYEN, MARIA-CLAUDIA; DE ANGELIS, KATIA. Exercise training initiated at old stage of lifespan attenuates aging-and ovariectomy-induced cardiac and renal oxidative stress: Role of baroreflex. Experimental Gerontology, v. 124, SEP 2019. (18/17183-4, 18/19006-2, 15/11223-6)