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

• Grant number: 21/09237-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: July 28, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Jarlei Fiamoncini
• Grantee: Larissa Rodrigues
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07914-8 - FoRC - Food Research Center, AP.CEPID
• Associated scholarship(s): 23/18077-1 - FLUXOMICS ANALYSIS TO ASSESS POSTPRANDIAL METABOLISM IN A MURINE MODEL: EFFECTS OF BILE ACIDS ON ISOLATED HEPATOCYTES, BE.EP.DR

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.

Scientific publications

(4)

(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)

DONADO-PESTANA, CARLOS M.; VASCONCELOS, AMANDA D.; MANTOVAM, VINICIUS B.; DE LIMA, GUSTAVO C.; RODRIGUES, LARISSA; BARBEIRO, HERMES, V; FOCK, RICARDO; DE SOUZA, HERALDO P.; FRANCO, BERNADETTE D. G. DE M.; FIAMONCINI, JARLEI. Circulating inflammatory markers linked to dysregulated postprandial metabolism in postmenopausal women. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 143, p. 9-pg., 2025-09-01. (23/02522-6, 21/09237-0, 22/02941-6, 22/08109-0, 20/16542-0, 13/07914-8)

DONADO-PESTANA, C. M.; RODRIGUES, L.; RUNDLE, M.; THOMAS, E. L.; WOPEREIS, S.; GUNDERSEN, T. E.; TREZZI, J. P.; BUNZEL, D.; KISELOVA-KANEVA, Y.; SONNTAG, D.; et al. Plasma metabolomic profiles reveal sex-specific response to an oral glucose tolerance test in late middle-aged adults. MECHANISMS OF AGEING AND DEVELOPMENT, v. 226, p. 12-pg., 2025-08-01. (20/16542-0, 21/09237-0, 22/02941-6)

PESSOA, ERIKA V. M.; MOURA, MARCIO H. C.; RODRIGUES, LARISSA; ROSSI E SILVA, RAFAELA; CASTRO, ERIQUE; FESTUCCIA, WILLIAM T.; DONADO-PESTANA, CARLOS M.; GENOVESE, MARIA INES. Jaboticaba (Plinia jaboticaba (Vell.) Berg) polyphenols alleviate skeletal muscle insulin resistance by modulating PI3K/Akt/GLUT-4 and AMPK signaling pathways in diet-induced obese mice. FOOD PRODUCTION PROCESSING AND NUTRITION, v. 6, n. 1, p. 9-pg., 2024-08-04. (21/09237-0, 20/16542-0, 13/07914-8)

DUARTE, STEPHANY GONCALVES; DONADO-PESTANA, CARLOS M.; MORE, TUSHAR H.; RODRIGUES, LARISSA; HILLER, KARSTEN; FIAMONCINI, JARLEI. Dry blood spots as a sampling strategy to identify insulin resistance markers during a dietary challenge. GENES AND NUTRITION, v. 19, n. 1, p. 9-pg., 2024-12-01. (21/09237-0, 20/16542-0, 22/02941-6, 21/08657-5)