Document Detail

Lipin-2 reduces proinflammatory signaling induced by saturated fatty acids in macrophages.
MedLine Citation:
PMID:  22334674     Owner:  NLM     Status:  MEDLINE    
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.
Martín Valdearcos; Esperanza Esquinas; Clara Meana; Lucía Peña; Luis Gil-de-Gómez; Jesús Balsinde; María A Balboa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-02-08
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-09-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10894-904     Citation Subset:  IM    
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.
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MeSH Terms
Cell Line
Cytokines / biosynthesis
Enzyme Activation / drug effects
Fatty Acids / metabolism,  pharmacology*
Inflammation / genetics,  metabolism,  pathology
JNK Mitogen-Activated Protein Kinases / metabolism
Macrophages / cytology*,  drug effects*,  metabolism
Monocytes / cytology
Nuclear Proteins / deficiency,  metabolism*
Phosphatidate Phosphatase / deficiency,  metabolism*
Signal Transduction / drug effects*
Transcription Factor AP-1 / metabolism
Triglycerides / metabolism
Up-Regulation / drug effects
Reg. No./Substance:
0/Cytokines; 0/Fatty Acids; 0/LPIN2 protein, human; 0/Nuclear Proteins; 0/Transcription Factor AP-1; 0/Triglycerides; EC Mitogen-Activated Protein Kinases; EC Phosphatase; EC 2 protein, mouse

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