title: Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages.
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.
authors.affiliation: Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, 47003 Valladolid and the Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, 08036 Barcelona, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Valdearcos
authors.forename: Esperanza
authors.initials: E
authors.lastname: Esquinas
authors.forename: Clara
authors.initials: C
authors.lastname: Meana
authors.forename: Lucía
authors.initials: L
authors.lastname: Peña
authors.forename: Luis
authors.initials: L
authors.lastname: Gil-de-Gómez
authors.forename: Jesús
authors.initials: J
authors.lastname: Balsinde
authors.forename: María A
authors.initials: MA
authors.lastname: Balboa
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000166:cytology; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D005227:Fatty Acids; C502575:LPIN2 protein, human; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014280:Triglycerides; D048031:JNK Mitogen-Activated Protein Kinases; D010711:Phosphatidate Phosphatase; C540254:Lipin 2 protein, mouse