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Distinct metabolic patterns during microglial remodeling by oleate and palmitate

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Author(s):
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.
Total Authors: 8
Document type: Journal article
Source: BIOSCIENCE REPORTS; v. 39, p. 15-pg., 2019-04-30.
Abstract

Microglial activation by oleate and palmitate differentially modulates brain inflammatory status. However, the metabolic reprogramming supporting these reactive phenotypes remains unknown. Employing real-time metabolic measurements and lipidomic analysis, we show that both fatty acids promote microglial oxidative metabolism, while lipopolysaccharide (LPS) enhances glycolytic rates. Interestingly, oleate treatment was followed by enrichment in storage lipids bound to polyunsaturated fatty acids (PUFA), in parallel with protection against oxidative imbalance. Palmitate, in turn, induced a distinct lipid distribution defined by PUFA linked to membrane phospholipids, which are more susceptible to lipid peroxidation and inflammatory signaling cascades. This distribution was mirrored by LPS treatment, which led to a strong pro-inflammatory phenotype in microglia. Thus, although both oleate and palmitate preserve mitochondrial function, a contrasting lipid distribution supports differences in fatty acid-induced neuroinflammation. These data reinforce the concept that reactive microglial profiles are achieved by stimulus-evoked remodeling in cell metabolism. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/07670-7 - Study of the metabolic reprograming sustaining microglial activation to inflammatory profiles
Grantee:Bruno Chausse de Freitas
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/25862-0 - Hepatic bioenergetics and redox signaling in obesity murine model: integrative analysis of nutritional, hormonal, and inflammatory stimuli
Grantee:Pâmela Aiako Hypólito Brito Kakimoto
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 15/21563-9 - Study of the paper uric acid and redox modulation on the system cell innate immune microbicide activity
Grantee:Railmara Pereira da Silva
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)