Involvement of acetate and bile acids on the prevention of glucose intolerance mediated by n-3 fatty acids

• Grant number: 11/21618-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2012
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Rui Curi
• Grantee: Jarlei Fiamoncini
• Supervisor: Hannelore Daniel
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Technical University of Munich (TUM), Germany
• Associated to the scholarship: 10/20322-4 - The role of peroxisomal function on the prevention of obesity and glucose intolerance, BP.PD

Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are associated with the prevention of insulin resistance. These molecules increase peroxisomal ²-oxidation of fatty acids (FA) and stimulate peroxisome proliferation in the liver through the activation of peroxisome proliferator activated receptors (PPAR). This project is based on the hypothesis that other than increasing peroxisomal FA ²-oxidation and acetil coA generation, peroxisome proliferation can also stimulate bile acids synthesis and free acetate formation. The excretion of excessive bile acids and free acetate could prevent that excessive intake of fat cause triacylglicerol accumulation in liver and other tissues. In this way, carbon skeletons that enter metabolism through the diet would be eliminated from the organism without being fully oxidised to CO2. Additionally, being the bile acids profile changed by n-3 PUFA intake, it is possible that they could modulate carbohydrate and lipid metabolism on a systemic level. In order to test this hypothesis, C57/Bl6 mice will be treated with hyperlipidic diets containing different concentrations of n-3 PUFA for 4 weeks. Acetate content in liver and urine and the plasmatic profile of bile acids will be quantified using chromatographic techniques associated with mass spectrometry. We are intendig to analyse also the expression pattern of genes related with peroxisomal metabolism of lipids to investigate which pathways are involved with the observed effects. If confirmed, these theories can become new mechanisms to explain the effects of n-3 PUFA on the prevention of obesity and glucose intolerance. (AU)