Lipin 1 represses NFATc4 transcriptional activity in adipocytes to inhibit secretion of inflammatory factors

Hyun Bae Kim, Anil Kumar, Lifu Wang, Guang Hui Liu, Susanna R. Keller, John C. Lawrence, Brian N. Finck, Thurl E. Harris

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Lipin 1 is a bifunctional protein that regulates gene transcription and, as a Mg2+-dependent phosphatidic acid phosphatase (PAP), is a key enzyme in the biosynthesis of phospholipids and triacylglycerol. We describe here the functional interaction between lipin 1 and the nuclear factor of activated T cells c4 (NFATc4). Lipin 1 represses NFATc4 transcriptional activity through protein-protein interaction, and lipin 1 is present at the promoters of NFATc4 transcriptional targets in vivo. Catalytically active and inactive lipin 1 can suppress NFATc4 transcriptional activity, and this suppression may involve recruitment of histone deacetylases to target promoters. In fat pads from mice deficient for lipin 1 (fld mice) and in 3T3-L1 adipocytes depleted of lipin 1 there is increased expression of several NFAT target genes including tumor necrosis factor alpha, resistin, FABP4, and PPARγ. Finally, both lipin 1 protein and total PAP activity are decreased with increasing adiposity in the visceral, but not subcutaneous, fat pads of ob/ob mice. These observations place lipin 1 as a potentially important link between triacylglycerol synthesis and adipose tissue inflammation.

Original languageEnglish
Pages (from-to)3126-3139
Number of pages14
JournalMolecular and cellular biology
Volume30
Issue number12
DOIs
StatePublished - Jun 2010

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