Papel dos adrenoreceptores Beta 3 na função cardiovascular, em marcadores metabólicos e de estresse oxidativo em modelo de síndrome metabólica

• Ano de defesa: 2019
• Autor(a) principal: Dias Junior, Eduardo [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Metabolic Syndrome; Fructose; Autonomic Nervous System; Receptor Beta 3 Adrenergic; Oxidative Stress; Síndrome Metabólica; Frutose; Sistema Nervoso Autônomo; Receptor Beta 3 Adrenérgico; Estresse Oxidativo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7656384; https://repositorio.unifesp.br/handle/11600/59748

Objective: to analyze the role of the adrenoreceptor ß3 (ARβ3) in the Metabolic Syndrome (MS) induced by fructose consumption. Methods: CEUA/UNIFESP: 6908290716; CEUA/UPM: 151/01/2017 – male mice after weaning (21 days, 18-22g) were assigned into 4 groups (n=15/group): Wild type FVB strain control and ARβ3 Knockout Control - free access to food and water for 8 weeks; Wild type FVB Strain Fructose and ARβ3 Knockout Fructose - free access to food and fructose added to the drinking water (10%) for 8 weeks. At the end of the experiment was performed: intraperitoneal glucose tolerance test and direct register of blood pressure (30min). The variability of the resultant signal was analyzed in frequency and time domains using spectral analysis. Blood samples and white adipose tissue, heart and liver were collected after euthanasia to: 1. White adipose tissue histology (Hematoxylin&Eosin); 2. Cardiac and hepatic oxidative profile; 3. Cardiac gene expression (TNFα, NFκß, Interleucin-1ß, NOS3 and adrenoceptors ß1 and ß2); 4. Serum lipid profile (calorimetric methods). The results were statistically analyzed by two-way ANOVA followed by Bonferroni post-test or Fisher’s LSD test. Results: Fructose induced glucose intolerance and hypertriglyceridemia in both mice strains. There were no alterations in final body weight, but fructose increased fat deposition only in the wild type animals, as well as adipocyte area. The lack of the ARß3 itself caused an increase in adipocyte area. Fructose did not cause alterations in blood pressure and heart rate, but increased blood pressure variability in the wild type animals and in its own sympathetic modulation in both mice strains. Furthermore, the lack of the ARβ3 increased heart rate variability and in its own sympathetic modulation followed by a decrease on parasympathetic modulation. When associated, the lack of the ARβ3 and fructose lead to a decrease in heart rate variability and in its own sympathetic modulation, followed by an increased in the parasympathetic modulation. Fructose caused hepatic lipidoxidation in both strains. Besides, the lack of the ARß3 induced a state of hepatic and cardiac oxidative stress. Gene expression found a cardiac inflammation state and an increase in adrenoreceptor ß2 and nitric oxide 3 due to the lack of ARß3 itself or when associated with fructose consumption. Conclusion: MS induced by fructose is not dependent of the ARβ3. However, the ARβ3 is essencial for the cardiovascular homeostasis and redox/oxidative balance.