| 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 |
| City of the host institution: | São Paulo |
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)
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