Lipin 1 Represses NFATc4 Transcriptional Activity in Adipocytes to Inhibit Secretion of Inflammatory Factors

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2010 Apr 14

PMID 20385772

Citations 69

Authors

Hyun Bae Kim

Anil Kumar

Lifu Wang

Guang-Hui Liu

Susanna R Keller

John C Lawrence Jr

Brian N Finck

Thurl E Harris

Affiliations

Soon will be listed here.

Abstract

Lipin 1 is a bifunctional protein that regulates gene transcription and, as a Mg(2+)-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 PPARgamma. 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.

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