Fructose overload in genitors: impact of exercise training on cardiometabolic and neuroimmune changes in offspring

• Grant number: 18/17183-4
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2019
• End date: August 31, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• 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

Nowadays, an exacerbated increase in fructose consumption has been observed due to its large use in the food industry, which seems to be related to the increase in the prevalence of metabolic syndrome. It is well known that high ingestion of fructose leads to increased adipose tissue, dyslipidemia, insulin resistance, hemodynamic and autonomic dysfunctions. Studies of our group have also shown that such dysfunctions are associated with inflammation, activation of the renin angiotensin system and oxidative stress, which can be attenuated by exercise training. Recently, the inflammatory cholinergic reflex has been described that seems to play an important role in the immunological responses, since this neural circuit is responsible for converting signals from the brain to the spleen, in a manner dependent on the alpha 7 subunit of the nicotinic acetylcholine receptor (alpha 7nAChR), decreasing the synthesis and release of proinflammatory cytokines systemically. However, despite the scientific advances in this area, we still do not know much about the impact of the exacerbated fructose consumption of the parents on the offspring, as well as the therapeutic potential of the exercise training in the prevention/treatment of this condition. Thus, the objective of this project will be: a) to evaluate cardiometabolic and neuroimmune parameters in offspring of Wistar rats submitted to fructose overload (10%); b) to test the role of the inflammatory cholinergic reflex, through splenectomy and vagotomy; c) investigate the impact of aerobic exercise training, a potential therapeutic approach, in modulating the possible neuroimmune alterations of the offspring. Initially, 28 Wistar rats will be used. Eighteen Wistar rats (4 males and 12 females) will undergo fructose overload (10%) in drinking water for a period of 60 days (from 30 to 90 days of life). The other 12 Wistar rats (3 males and 9 females) will only be followed for the same 60 days receiving water. After this period, each male rat will be allocated in an appropriate cage with 3 females to provide mating. Fructose overload will be maintained for females until the end of the lactation period. The day of birth of the offspring will be considered as day 0 of the study, which will be divided into 3 protocols. In protocol 1, the neonates of genitors treated with water (n = 24) or fructose (n = 24) will be evaluated and compared. In protocol 2, the offspring of rats treated with water or fructose on the last day of weaning and 7, 14 and 30 days after weaning (n = 10 animals, 5 males and 5 females per time/per group) were evaluated and compared. In protocol 3, vagatomy of celic branch or splenectomy, associated or not to exercise training (an approach with therapeutic potential), will be performed in the offspring of animals treated with fructose on the day of weaning, and they will be evaluated 30 days after this procedure and compared with the groups protocol 2. Metabolic, hemodynamic, autonomic, inflammatory, renin-angiotensin system and oxidative stress parameters will be evaluate systemically and in the cardiac and splenic tissues in all three protocols. The results obtained in the present study may contribute to the knowledge of the influence of the cardiometabolic health of the parents on their offspring, and could support future therapeutic strategies such as exercise training in the management of offspring dysfunctions. (AU)

Scientific publications

(11)

(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)

DIAS, DANIELLE DA SILVA; BERNARDES, NATHALIA; STOYELL-CONTI, FILIPE FERNANDES; DOS SANTOS, CAMILA PAIXAO; DE ARAUJO, AMANDA APARECIDA; LLESUY, SUSANA; IRIGOYEN, MARIA CLAUDIA; DE ANGELIS, KATIA. Impact of combined exercise training on the development of cardiometabolic and neuroimmune complications induced by fructose consumption in hypertensive rats (vol 15, e0233785, 2020). PLoS One, v. 15, n. 7, p. 1-pg., 2020-07-06. (18/17183-4, 15/11223-6)

DOS SANTOS, CAMILA; ARAUJO, AMANDA; DIAS, DANIELLE; SILVA, DEIWET; SHECAIRA, TANIA; DUTRA, MARINA; SILVA, MAIKON; IRIGOYEN, MARIA; DE ANGELIS, KATIA. Excessive Ingestion Of Parental Fructose Causes Autonomic Dysfunction Since Birth In Offspring: Impact on Adulthood. FASEB JOURNAL, v. 34, p. 2-pg., 2020-04-01. (18/17183-4)

DOS SANTOS, CAMILA PAIXAO; SILVA, DEIWET RIBEIRO; DIAS, DANIELLE DA SILVA; ARAUJO, AMANDA; BERNARDES, NATHALIA; CONTI, FILIPE FERNARDES; IRIGOYEN, MARIA CLAUDIA; DE ANGELIS, KATIA. Parents exacerbated fructose intake causes early cardiovascular autonomic dysfunctions in offspring. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (18/17183-4)

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)

BRITO-MONZANI, JANAINA DE OLIVEIRA; STOYELL-CONTI, FILIPE FERNANDES; SHECAIRA, TANIA PLENS; SILVA, MICHEL PABLO DOS SANTOS FERREIRA; DIAS, DANIELLE DA SILVA; BERNARDES, NATHALIA; DE ANGELIS, KATIA. Aerobic or resistance training improves autonomic control of circulation in oophorectomized rats with cardiometabolic dysfunctions: Impact on renal oxidative stress. Experimental Gerontology, v. 145, MAR 2021. (18/17183-4, 12/20141-5, 10/17188-4)

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)

S.C.F. FREITAS; C. PAIXÃO DOS SANTOS; A. ARNOLD; F.F. STOYELL-CONTI; M.R.H. DUTRA; M. VERAS; M.C. IRIGOYEN; K. DE ANGELIS. A method to assess heart rate variability in neonate rats: validation in normotensive and hypertensive animals. Brazilian Journal of Medical and Biological Research, v. 53, n. 8, 2020-06-26. (18/19006-2, 18/17183-4)

DIAS, DANIELLE DA SILVA; DOS SANTOS, CAMILA P.; ARAUJO, AMANDA A.; FERREIRA, MAYCON J.; NASCIMENTO-FILHO, ANTONIO V.; BERNARDES, NATHALIA; IRIGOYEN, MARIA CLAUDIA; DE ANGELIS, KATIA. Cardiovascular and autonomic profiles in offspring of fructose fed parents: role of anti-inflammatory cholinergic reflex and exercise training. FASEB JOURNAL, v. 36, p. 1-pg., 2022-01-01. (18/17183-4)

DIAS, DANIELLE; DOS SANTOS, CAMILA; ARAUJO, AMANDA; FERREIRA, MAYCON; SHECAIRA, TANIA; CARMO, GABRIEL; BERNARDES, NATHALIA; IRIGOYEN, MARIA; DE ANGELIS, KATIA. Effects of exercise training on metabolic and cardiovascular dysfunctions in offspring of fructose animals: role of cholinergic anti-inflammatory reflex. FASEB JOURNAL, v. 34, p. 2-pg., 2020-04-01. (18/17183-4)

BERNARDES, NATHALIA; DIAS, DANIELLE; STOYELL-CONTI, FILIPE; FREITAS, SARAH; PAIXAO, CAMILA; LLESUY, SUSANA; IRIGOYEN, MARIA-CLAUDIA; DE ANGELIS, KATIA. TIME COURSE CARDIOVASCULAR AND NEUROIMMUNE DYSFUNCTIONS IN A METABOLIC SYNDROME MODEL: IMPACT OF AEROBIC TRAINING. FASEB JOURNAL, v. 34, p. 2-pg., 2020-04-01. (18/17183-4)

FERREIRA, MAYCON JUNIOR; SANCHES, IRIS CALLADO; JORGE, LUCIANA; LLESUY, SUSANA FRANCISCA; IRIGOYEN, MARIA CLAUDIA; DE ANGELIS, KATIA. Ovarian status modulates cardiovascular autonomic control and oxidative stress in target organs. BIOLOGY OF SEX DIFFERENCES, v. 11, n. 1, APR 7 2020. (18/17183-4)