FLUXOMICS ANALYSIS TO ASSESS POSTPRANDIAL METABOLISM IN A MURINE MODEL: EFFECTS OF BILE ACIDS ON ISOLATED HEPATOCYTES

• Grant number: 23/18077-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 01, 2024
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Jarlei Fiamoncini
• Grantee: Larissa Rodrigues
• Supervisor: Karsten Hiller
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Technology Braunschweig, Germany
• Associated to the scholarship: 21/09237-0 - Postprandial metabolism and inflammation: the role of bile acids as signaling molecules, BP.DR

Abstract

After the ingestion of a meal, changes in plasma levels of nutrients, endogenous metabolites and signaling molecules trigger changes in several physiological processes, affecting energy metabolism and inducing a transient inflammatory response. The increase in plasma levels of bile acids (BA) is one of the most remarkable changes in plasma metabolome in the postprandial period, although its consequences to metabolism are largely unknown. The effects of BA in vivo models are little studied, despite the evidence supporting their role as modulators of inflammation and metabolism from in vitro studies. This proposal aims to identify the effects of BA on metabolism during the postprandial period in Sprague-Dawley rats. Two separate experiments are planned: the first investigates the effects of an acute dose of cholic acid (the most abundant BA in rat plasma) on postprandial metabolism and inflammation at a systemic level, while the second assesses metabolism and inflammation in liver cells isolated during the postprandial period. For both experiments, rats ingested a mixed meal after an overnight fasting and were culled at fasting, 1, 2, 3 and 5 hours after food intake followed or not by an oral dose of cholic acid. 13C-labelled glucose was included in the meal to track metabolic fluxes of the most important pathways of energy metabolism (fluxomics analysis). This proposal encompasses the workplan for a 12-month internship (BEPE) under the supervision of Prof. Kasten Hiller at the Technical University of Braunschweig, Germany. At Prof. Hiller's group, we will carry out the analysis of 13C-labelled metabolites derived from the ingested 13C-labelled glucose to assess the activity of metabolic pathways such as glycolysis, TCA cycle, glycogen and fatty acid synthesis. The proposed study will provide new data, contributing to fill the gaps in the understanding of postprandial metabolic changes and the role of BA in the regulation of energy metabolism and inflammation.