Control of glycerol-3-phosphate generation and fatty acid esterification in liver and white and brown adipose tissues

• Grant number: 06/00448-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2006
• End date: May 31, 2009
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Isis Do Carmo Kettelhut
• Grantee: Isis Do Carmo Kettelhut
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The main objective of the project is to clarify the mechanisms through which the generation of the glycerol-3-phosphate (G3P) needed for fatty acid (FA) esterification and triacylglycerol (TAG) synthesis is controlled in three tissues directly involved in caloric homeostasis: white (WAT) and brown (BAT) adipose tissues, and liver. The traditional and generally recognized source of G3P is glucose, through reduction of dihydroxyacetone-P in the glycolytic pathway. Recent work from this laboratory demonstrated the importance for the lipid metabolism of those three tissues of two other sources of G3P, hitherto little investigated: non-glycidic substrates (lactate, amino acids), by a partial reversion of glycolysis (glyceroneogenesis) and glycerol, directly phosphorylated by glycerokinase (GK). In continuation to previous work, the experiments in the project were designed to investigate in WAT, BAT and liver in vitro, and when possible, in vivo, the three pathways of G3P generation in the following experimental conditions: fasting, diabetes, adaptation to a high protein, carbohydrate-free (HP) diet, a hyperlipidic, hypercaloric (HLHC) diet, and cold exposure. The specific objectives are based on previous results and can be summarized as follows: a) to verify the effect of WAT and liver denervation on the activity of the three pathways b) to verify the role of preformed FA in the activation of glyceroneogenesis in the three tissues c) to verify if the effect of epididymal WAT denervation (hitherto never investigated) is similar to that of retroperitoneal WAT denervation d) to investigate the sympathetic control of WAT GK activity e) to investigate the role of insulin in the effects produced by the HLHC diet. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FRASSON, DANUBIA; BOSCHINI, RENATA POLESSI; CHAVES, VALERIA ERNESTANIA; SOARES MARTINS DOS SANTOS, MARIA EMILIA; GOMES, SILVIA DE PAULA; VALENTIM, RAFAEL ROSSI; RISSATO GAROFALO, MARIA ANTONIETA; CARVALHO NAVEGANTES, LUIZ CARLOS; MIGLIORINI, RENATO HELIOS; KETTELHUT, ISIS DO CARMO. The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats. METABOLISM-CLINICAL AND EXPERIMENTAL, v. 61, n. 10, p. 1473-1485, OCT 2012. (06/00448-8, 10/12206-4)