Study of the metabolic reprograming sustaining microglial activation to inflammatory profiles

• Grant number: 15/07670-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2015
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Bruno Chausse de Freitas
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Microglia are innate immune cells resident in the central nervous system, whose activation has been related to chronic pathologies such as Parkinson's disease and obesity. Recent evidences suggest that microglial activation is supported by decreases in oxidative metabolism a long with enhancements in anaerobic glycolysis. Nonetheless, the metabolic reprograming sustaining microglial inflammatory profiles are not fully understood. Here, we aim to evaluate the mechanistic connection between metabolic and redox pathways that supports microglial activation to proinflammatory profiles induced by LPS and nutrient excess. Preliminary results suggest that mitochondrial function loss, a marker of LPS-induced microglial activation, occurs in a progressive manner and that cytosolic oxidant production precedes changes in oxidative metabolism. In addition, part of the inflammatory response seems to be modulated independently of metabolic alterations. Further results suggest that, in contrast to LPS, nutrient excess induces the expression of anti-inflammatory markers in parallel to enhancements in mitochondrial function. To detail the mechanistic connection between metabolic and redox pathways underlying microglial activation, next experiments include the evaluation of alterations in oxidative balance and mitochondrial morphology and function sustaining these inflammatory profiles.

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)

CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; CALDEIRA-DA-SILVA, CAMILLE C.; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; DA SILVA, RAILMARA PEREIRA; MIYAMOTO, SAYURI; KOWALTOWSKI, ALICIA J.. Distinct metabolic patterns during microglial remodeling by oleate and palmitate. BIOSCIENCE REPORTS, v. 39, p. 15-pg., 2019-04-30. (13/07937-8, 15/07670-7, 15/25862-0, 15/21563-9)

CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; CALDEIRA-DA-SILVA, CAMILLE C.; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; DA SILVA, RAILMARA PEREIRA; MIYAMOTO, SAYURI; KOWALTOWSKI, ALICIA J.. Distinct metabolic patterns during microglial remodeling by oleate and palmitate. BIOSCIENCE REPORTS, v. 39, n. 4, APR 30 2019. (13/07937-8, 15/07670-7, 15/21563-9, 15/25862-0)

ALSABEEH, NOUR; CHAUSSE, BRUNO; KAKIMOTO, PAMELA A.; KOWALTOWSKI, ALICIA J.; SHIRIHAI, ORIAN. Cell culture models of fatty acid overload: Problems and solutions. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1863, n. 2, p. 143-151, FEB 2018. (13/07937-8, 15/07670-7, 15/25862-0)

KAKIMOTO, PAMELA A.; CHAUSSE, BRUNO; CALDEIRA DA SILVA, CAMILLE C.; DONATO JUNIOR, JOSE PRIME; KOWALTOWSKI, ALICIA J.. Resilient hepatic mitochondria! function and lack of iNOS dependence in diet-induced insulin resistance. PLoS One, v. 14, n. 2, FEB 4 2019. (13/07937-8, 17/18972-0, 15/25862-0, 15/07670-7)