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Title

Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages

AuthorsValdearcos, Martín ; Esquinas, Esperanza ; Meana, Clara ; Peña, Lucía ; Gil-de-Gómez, Luis ; Balsinde, Jesús ; Balboa, María A.
Issue Date2012
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 287(14): 10894-10904 (2012)
AbstractLipin-2 is a member of the lipin family of enzymes, which are key effectors in the biosynthesis of lipids. Mutations in the humanlipin-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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M112.342915
URIhttp://hdl.handle.net/10261/116596
DOI10.1074/jbc.M112.342915
Identifiersdoi: 10.1074/jbc.M112.342915
issn: 0021-9258
e-issn: 1083-351X
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