Document Detail

Thematic Review Series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism.
MedLine Citation:
PMID:  18791037     Owner:  NLM     Status:  MEDLINE    
Phosphatidate phosphatase-1 (PAP1) enzymes have a key role in glycerolipid synthesis through the conversion of phosphatidate to diacylglycerol, the immediate precursor of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. PAP1 activity in mammals is determined by the lipin family of proteins, lipin-1, lipin-2, and lipin-3, which each have distinct tissue expression patterns and appear to have unique physiological functions. In addition to its role in glycerolipid synthesis, lipin-1 also operates as a transcriptional coactivator, working in collaboration with known nuclear receptors and coactivators to modulate lipid metabolism gene expression. The requirement for different lipin activities in vivo is highlighted by the occurrence of lipodystrophy, insulin resistance, and neuropathy in a lipin-1-deficient mutant mouse strain. In humans, variations in lipin-1 expression levels and gene polymorphisms are associated with insulin sensitivity, metabolic rate, hypertension, and risk for the metabolic syndrome. Furthermore, critical mutations in lipin-2 result in the development of an inflammatory disorder in human patients. A key goal of future studies will be to further elucidate the specific roles and modes of regulation of each of the three lipin proteins in key metabolic processes, including triglyceride and phospholipid synthesis, fatty acid metabolism, and insulin sensitivity.
Karen Reue; David N Brindley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2008-09-12
Journal Detail:
Title:  Journal of lipid research     Volume:  49     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2009-02-09     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2493-503     Citation Subset:  IM    
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
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MeSH Terms
Adipose Tissue / metabolism
Genetic Variation
Insulin Resistance
Lipid Metabolism / physiology*
Liver / metabolism
Models, Biological
Muscles / metabolism
Phosphatidate Phosphatase / metabolism*
Grant Support
Reg. No./Substance:
EC Phosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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