Metabolismo do tecido adiposo marrom em modelos de resistência à insulina: ratos diabéticos Goto Kakizaki e obesos Wistar.

• Ano de defesa: 2020
• Autor(a) principal: Serdan, Tamires Duarte Afonso
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Cruzeiro do Sul; Brasil; Programa de Pós Graduação em Ciências da Saúde; Cruzeiro do Sul
• Palavras-chave em Português: Obesidade; Diabetes mellitus; Termogênese; Expressão gênica; Batocinas; CNPQ::CIENCIAS DA SAUDE
• Link de acesso: https://repositorio.cruzeirodosul.edu.br/handle/123456789/2494

The brown adipose tissue (BAT) has been proposed as a targeted treatment of obesity due to the high metabolic activity to dissipates energy as heat, thus increasing energy expenditure. BAT responds to insulin and its activation plays an important role in glucose homeostasis, but the mechanisms involved are not yet fully understood. The aim of this study was to evaluate the BAT function in animal models of IR: obese animals (Wistar rats fed to a high-fat diet or high-fat diet plus condensed milk) and non-obese animals (Goto-Kakizaki rats, genetically predisposed to IR). The following were investigated: 1) Gene expression of genes involved in the glucose and fatty acids metabolism (GLUT-1, GLUT-4, UCP-1, CPT1, CPT2, FASN, phosphofructokinase, citrate synthase), insulin signaling pathway (insulin receptor, IRS -1, IRS-2, Akt, GSK-3b, MAPKs), batokines (FGF21), genes related to inflammation and obesity (GPx-1, PAI-1, PPARs, PGC-1, adiponectin, resistin, and leptin), and related in TAM activity (Dio2, SIRT1 and Cidea, and Adrb3). 2) The activation of proteins related to the insulin signaling pathway (GSK-3b and p-AMPK), mitochondrial proteins (Mitofusin 2, OXPHOS, and UCP-1) and proteins TAM metabolism (PPARa and FGF21), by the technique western blot to measures content of total and phosphorylated proteins. 3) TAM metabolism by PETCT, mitochondrial oxygen consumption, and thermography. 4) Histological analysis of BAT. GK animals showed increased (p < 0.05) mRNA expression of genes involved in fatty acid oxidation (CPT1, CPT2, and CS), insulin signaling pathway (IRS-2 and MAPK3), glucose uptake (GLUT4), BAT metabolism (Cidea), and obesogenic genes (leptin, PFK, and PAI-1), but showed a decreased (p < 0.05) expression of genes involved in glucose uptake (GLUT1), adipogenesis (resistin and adiponectin), and b3-adrenergic receptor (Adrb3). We observed increased protein content of Mitofusin 2 in GK animals compared to NL and HL groups; however, less mitochondrial activity by respirometry. In addition, we observed low 18F-FDG uptake after adrenergic stimulus, assessed by PET-CT and a greater adipocytes area, and a greater area of lipids droplets of BAT in GK animals. Our data are indicative that thermogenic activity, glucose uptake, and morphology of BAT are impaired in GK animals, suggesting a transition from TAM to TAB, a process known as “whitening”.