Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages.
J Biol Chem
; 287(14): 10894-904, 2012 Mar 30.
Article
em En
| MEDLINE
| ID: mdl-22334674
ABSTRACT
Lipin-2 is a member of the lipin family of enzymes, which are key effectors in the biosynthesis of lipids. Mutations in the human lipin-2 gene are associated with inflammatory-based disorders; however, the role of lipin-2 in cells of the immune system remains obscure. In this study, we have investigated the role of lipin-2 in the proinflammatory action of saturated fatty acids in murine and human macrophages. Depletion of lipin-2 promotes the increased expression of the proinflammatory genes Il6, Ccl2, and Tnfα, which depends on the overstimulation of the JNK1/c-Jun pathway by saturated fatty acids. In contrast, overexpression of lipin-2 reduces the release of proinflammatory factors. Metabolically, the absence of lipin-2 reduces the cellular content of triacylglycerol in saturated fatty acid-overloaded macrophages. Collectively, these studies demonstrate a protective role for lipin-2 in proinflammatory signaling mediated by saturated fatty acids that occurs concomitant with an enhanced cellular capacity for triacylglycerol synthesis. The data provide new insights into the role of lipin-2 in human and murine macrophage biology and may open new avenues for controlling the fatty acid-related low grade inflammation that constitutes the sine qua non of obesity and associated metabolic disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidato Fosfatase
/
Proteínas Nucleares
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Transdução de Sinais
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Ácidos Graxos
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Macrófagos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Espanha