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Effects of aerobic exercise training and treatment with galantamine in the offspring of rats submitted to fructose overload: role of the cholinergic anti-inflammatory reflex


Studies have reported increased consumption of manufactured foods containing high concentrations of fructose, which has been associated with the development of metabolic syndrome (MS). Experiments carried out by our group showed that rats submitted to chronic consumption of fructose presented insulin resistance and hemodynamic and autonomic dysfunctions associated with an inflammatory and oxidative stress profile. In this sense, the cholinergic anti-inflammatory reflex pathway seems to play an important role in the immune response. In models of systemic inflammation, it has been shown that this pathway, when activated through vagal electrical stimulation or by cholinergic agonists, reduces the synthesis of pro-inflammatory cytokines, just as vagotomy and splenectomy (S) abolish this effect. Galantamine (GAL), a drug that acts on cholinergic neurons of the central nervous system, also regulates the activity of the anti-inflammatory cholinergic pathway. In addition, the beneficial cardiometabolic and autonomic effects of aerobic exercise training (AET) are well known. However, little is known about the impact of parental fructose consumption on their offspring, the role of the anti-inflammatory cholinergic pathway, as well as the effects of AET in this scenario. Thus, the objectives of this project will be: 1) to investigate the participation of the cholinergic anti-inflammatory reflex, through splenectomy (S), splenic denervation (D) and treatment with GAL (a positive control) in neuroinflammatory and oxidative stress changes in offspring of parents of rats submitted to chronic fructose consumption (protocol 1); and 2) to evaluate the effects of AET, a well known non-pharmacological approach, to managing autonomic and inflammatory dysfunctions in this condition (protocol 2). Wistar rats (parents) will be subjected to fructose overload in drinking water (10%) or water consumption for 60 days. Then the rats will be placed in boxes to facilitate mating. Fructose overload for females will be maintained until the end of lactation. At 21 days of life (end of lactation) the offspring of the parents will be divided into groups (5 males and 5 females per group) for protocol 1: control (CG), fructose (FG), fructose+S (FSG), fructose+D (FDG), fructose+GAL (5mg/Kg, FGG), fructose+D+GAL (FDGG); protocol 2: CG, FG, FDG fructose+AET (FTG) and fructose+D+TFA (FDTG). All groups will be evaluated and compared after 35 days of weaning regarding metabolic, hemodynamic, neuroinflammatory (autonomic and inflammatory) and oxidative stress parameters. The results of this study may contribute to the knowledge of the mechanisms associated with cardiometabolic disorders associated with the development of MS, as well as serve as a basis for the search for future therapeutic strategies, positively impacting the quality of life. (AU)

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