Estudo da via de sinalização da grelina e sua ação no metabolismo energético do tecido adiposo marrom de camundongos obesos hiperalimentados na lactação

• Autor(a) principal: Malafaia, Tayanne de Oliveira
• Data de Publicação: 2018
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/12709
• topic: Obesity; Ghrelin; Overfed; Brown adipose tissue; Metabolic programming; Obesidade; Grelina; Hiperalimentação; Tecido adiposo marrom; Programação metabólica; Obesidade - Metabolismo; Grelina - Metabolismo; Metabolismo energético; Hiperfagia; Tecido adiposo marrom; Camundongo como animal de laboratório; CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS

Obesity is one of the major public health problems resulting from an imbalance between food intake and energy expenditure. The increase in adiposity leads to the development of dyslipidemias, cardiovascular diseases and type 2 diabetes, besides favoring the emergence of potentially lethal diseases in the reduction of quality and life expectancy. The hormone ghrelin is synthesized by the stomach and acts on different tissues through a specific receptor (GHS-R1a), including the hypothalamus and brown adipose tissue (BAT). It is also involved in eating behavior and adiposity, modulating the storage or use of energetic substrates in adipocytes. It is known that BAT plays an important role in the regulation of energetic metabolism and that obese animals that were overnutrition during lactation present changes in the thermogenic activity of this tissue and lower secretion of plasma ghrelin. Therefore, considering that neonatal overnutrition induces obesity in adulthood by mechanisms not yet fully elucidated, in this study we investigated the effects of acylated ghrelin on biochemical parameters and protein analysis in BAT of hyperalimentary adult animals in early life. Overfed Swiss mice were used through the litter reduction model. To induce overnutrition the litters were reduced to 3 male pups per infant on the 3rd day postnatal life (overfed group - OG). The control litters were adjusted in 6 pups per infant (control group - CG). At 120 days the control and overfed groups were subdivided into animals receiving infusion of ghrelin (3nM) (GC-Gre and GH-Gre) or saline (GC-Sal and GH-Sal) for one hour fasting. Anthropometric parameters such as: body mass and visceral adipose tissue mass, liver and BAT weight were evaluated. We evaluated biochemical and hormonal parameters such as glycemia, insulin, acylated ghrelin, hepatic glycogen, triglycerides and total cholesterol. Through the Western Blotting technique, we evaluated the content of important proteins in mitochondrial metabolism, in the signaling pathway of insulin and ghrelin. Through high resolution respirometry we verify the mitochondrial respiratory flow rate of the animals. The data demonstrate that overnutrition induces a significant increase in body weight, visceral fat and hyperglycemia in adult animals. Administration of ghrelin increased glycemia in adult control (CG-Ghre) animals. In the obese, ghrelin promoted a reduction in glycemia when compared to OG-Sal. Plasma levels of insulin were not altered after administration of ghrelin, but there was an increase in hepatic glycogen in the control group and reduction in overfed (OG-Ghre), when compared to CG-Sal and OG-Sal, respectively. In addition, in brown adipose tissue, we observed that ghrelin promoted a reduction of the UCP1 and GHSR1a contents of the control animals when compared to the CG-Sal. Basically, we have shown that ghrelin infusion is involved in regulating glycemia, the ghrelin signaling pathway, and the modulation of thermogenic activity in BAT in control and hyperalimentary adult animals, suggesting that ghrelin is a hormone that acts differently depending on the nutritional status of the animal.