Sirtuínas e inflamação: efeitos metabólicos de um novo hidroxibutenolideo e papel do resveratrol no cérebro e cognição

Abstract

Obesity is one of the main health problems worldwide. Its epidemiological incidence is increasing, as is the mortality due to metabolic diseases and comorbidities such as metabolic syndrome and type 2 diabetes mellitus. Sirtuins are histone deacetylases regulatory enzymes of genetic material, deeply involved in numerous physiological tasks, including metabolism, brain function and aging. . The objective of this work is to evaluate the metabolic effects of Hydroxybutenolide (3-chloro-4-(p chlorophenylsulfonylamino-5-hydroxyfuran-2(5H)-one) in an animal model of obesity induction and to evaluate the role of resveratrol in cognition, brain and sirtuins.The thesis is divided into an experimental research carried out with an animal model (Swis mice) of obesity and metabolic syndrome induction and a systematic review on sirtuins and brain.The animals were divided into SD, SD+FS; HF and HF+FS and obesity induction lasted 13 weeks. The drug was administered by gavage at a dose of 70 mg/kg/day for 30 days, data on body weight, food consumption and glycemic tests were collected. After euthanasia of the animals, the biochemical dosages were measured, tissue collection and storage, histology, measurement of the white adipose tissue adipocyte area and RT-PCR for the SIRT1, SIRT3, SIRT5 and NFKβ genes. T of Stu dent, the results were presented in absolute and relative values, using mean and standard deviation and presented in graphs and figures. Body weight values decreased after drug treatment (ST+LS: -7.81 ±4.39, p = 0.0247 and HF+FS: -11.77 ±9.59, p = 0.0334). In both glycemic tests and fasting glucose, the values for the treated groups were lower (p<0.05). Adipose (ST+FS: 0.017 ±0.011; HF+FS: 0.062 ±0.017) and epididymal white adipose tissue volume decreased in the groups that received the drug, as well as the adipocyte area for the HF+FS group. The expression of SIRT1 was higher in the groups that received hydroxybutenolide. The most studied sirtuin is SIRT1, which plays an essential role in the prevention and evolution of neurodisorders. Resveratrol is a polyphenol, which belongs to a family of compounds identified as stilbenes, predominantly concentrated in grapes and red wine. Treatment with 3- chloro-4-(p-chlorophenylsulfonylamino)-5-hydroxyfuran-2(5H)-one promoted a decrease in body weight and white adipose tissue volume; smaller area of adipocytes; improved glucose metabolism and decreased triglycerinemia and overexpression of SIRT1. Like the new hydroxybutenolide tested, resveratrol is a natural substance with several proven beneficial effects, including the activation of sirtuins that contribute to the prevention of cognition problems and neurodegenerative diseases.