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Artículo

Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages

Quiroga, Ivana YoseliIcon ; Pellon Maison, MagaliIcon ; Suchanek, Amanda L.; Grandinetti, Rosalinda; Gonzalez Baro, Maria del RosarioIcon
Fecha de publicación: 01/2019
Editorial: Portland Press
Revista: Biochemical Journal
ISSN: 0264-6021
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Macrophage classical M1 activation via TLR4 triggers a variety of responses to achieve the elimination of foreign pathogens. During this process, there is also an increase in lipid droplets which contain large quantities of triacylglycerol (TAG) and phospholipid (PL). The functional consequences of this increment in lipid mass are poorly understood. Here, we studied the contribution of glycerolipid synthesis to lipid accumulation, focusing specifically on the first and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase (GPAT). Using bone marrow-derived macrophages (BMDMs) treated with Kdo 2 -lipid A, we showed that glycerolipid synthesis is induced during macrophage activation. GPAT4 protein level and GPAT3/GPAT4 enzymatic activity increase during this process, and these two isoforms were required for the accumulation of cell TAG and PL. The phagocytic capacity of Gpat3 −/− and Gpat4 −/− BMDM was impaired. Additionally, inhibiting fatty acid β-oxidation reduced phagocytosis only partially, suggesting that lipid accumulation is not necessary for the energy requirements for phagocytosis. Finally, Gpat4 −/− BMDM expressed and released more pro-inflammatory cytokines and chemokines after macrophage activation, suggesting a role for GPAT4 in suppressing inflammatory responses. Together, these results provide evidence that glycerolipid synthesis directed by GPAT4 is important for the attenuation of the inflammatory response in activated macrophages.
Palabras clave: KDO-LIPID A , CYTOKINES , LIPID DROPLETS , PHAGOCYTOSIS
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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
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URI: http://hdl.handle.net/11336/130106
DOI: https://doi.org/10.1042/BCJ20180381
URL: https://portlandpress.com/biochemj/article-abstract/476/1/85/88/Glycerol-3-phosp
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Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Quiroga, Ivana Yoseli; Pellon Maison, Magali; Suchanek, Amanda L.; Grandinetti, Rosalinda; Gonzalez Baro, Maria del Rosario; Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages; Portland Press; Biochemical Journal; 476; 1; 1-2019; 85-99
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