Journal
PROGRESS IN LIPID RESEARCH
Volume 52, Issue 3, Pages 305-316Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2013.04.001
Keywords
Glycerolipid synthesis; Phosphatidic acid; Diacylglycerol; Gene family; Gene mutation; Lipodystrophy
Funding
- United States Public Health Service [HL090553, HL028481, T32HG002536]
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Members of the lipin protein family are phosphatidate phosphatase (PAP) enzymes, which catalyze the dephosphorylation of phosphatidic acid to diacylglycerol, the penultimate step in TAG synthesis. Lipins are unique among the glycerolipid biosynthetic enzymes in that they also promote fatty acid oxidation through their activity as co-regulators of gene expression by DNA-bound transcription factors. Lipin function has been evolutionarily conserved from a single ortholog in yeast to the mammalian family of three lipin proteins-lipin-1, lipin-2, and lipin-3. In mice and humans, the levels of lipin activity are a determinant of TAG storage in diverse cell types, and humans with deficiency in lipin-1 or lipin-2 have severe metabolic diseases. Recent work has highlighted the complex physiological interactions between members of the lipin protein family, which exhibit both overlapping and unique functions in specific tissues. The analysis of lipinopathies in mouse models and in humans has revealed an important role for lipin activity in the regulation of lipid intermediates (phosphatidate and diacylglycerol), which influence fundamental cellular processes including adipocyte and nerve cell differentiation, adipocyte lipolysis, and hepatic insulin signaling. The elucidation of lipin molecular and physiological functions could lead to novel approaches to modulate cellular lipid storage and metabolic disease. (C) 2013 Elsevier Ltd. All rights reserved.
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