Postprandial metabolism and inflammation: the role of bile acids as signaling molecules

Abstract

Bile acids (BA) are amphipathic molecules derived from cholesterol catabolism, recently recognized as metabolic integrators, participating in the regulation of energy metabolism (including the inhibition of gluconeogenesis and stimulation of fatty acid ²-oxidation) and inflammation through hormone-like functions. Among the endogenous metabolites, BA are those whose plasma concentration show the largest variation after the ingestion of a meal. Postprandial inflammation, hyperlipemia, and hyperglycemia are risk factors for the development of chronic diseases, but have been neglected by studies that focus in samples collected after an overnight fasting, therefore lacking information derived from the response to a meal. Given their regulatory effects and postprandial plasma kinetics that resemble signaling compounds such as insulin and incretins, we propose to investigate whether BA can influence postprandial metabolic and inflammatory responses in Sprague Dawley rats submitted to dietary challenges. Four experiments will be conducted as part of this proposal: 1) a characterization of postprandial plasma kinetics of BA when rats are challenged with meals with different macronutrient composition. 2) A study to evaluate the development of the postprandial inflammatory and metabolic responses in different tissues and organs, investigating the role of BA in these processes. 3) A third study will deepen the investigation about the effects of BA on the postprandial metabolism and inflammation, analyzing postprandial metabolic responses when rats are given a dose of ursodeoxycholic acid in its free and taurine-conjugated forms. 4) The last study will assess postprandial responses in metabolism and function of hepatocytes and Kupffer cells isolated from rats after the ingestion of meals supplemented or not with BA. This original proposal will study the relationship between BA and physiological processes regulated in the postprandial period, with potential to make novel contributions to the field. We expect to deliver the characterization of an animal model to study the effects of BA in postprandial physiology and generate new information about the regulation of metabolism and inflammation in an organ- and tissue-specific manner at different time points during the postprandial period.