J. Lipid Res.
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A more recent version of this article appeared on May 1, 2008 Originally published In Press as doi:10.1194/jlr.M800013-JLR200 on February 15, 2008

Papers In Press, published online ahead of print February 2, 2008
J. Lipid Res., doi:10.1194/jlr.M800013-JLR200
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Submitted on January 11, 2008
Revised on January 31, 2008
Accepted on February 2, 2008

Glucocorticoids and cAMP selectively increase hepatic lipin-1 expression and insulin acts antagonistically

Boripont Manmontri, Meltem Sariahmetoglu, Jimmy Donkor, Maroun Bou Khalil, Meenakshi Sundaram, Zemin Yao, Karen Reue, Richard Lehner, and David N. Brindley

Biochemistry, University of Alberta, Edmonton, AB T6G-2S2

Corresponding Author: david.brindley{at}ualberta.ca

Glucocorticoids increase hepatic phosphatidate phosphatase-1 (PAP1) activity. This is important in enhancing the liver’s capacity for storing fatty acids as triacylglycerols that can be used subsequently for ß-oxidation or VLDL secretion. PAP-1 catalyzes the conversion of phosphatidate to diacylglycerol, a key substrate for triacylglycerol and phospholipid biosynthesis. PAP1 enzymes in liver include lipin-1A and -1B (alternatively spliced isoforms) and two distinct gene products, lipin-2 and lipin-3 (Donkor et al. (2007) J. Biol. Chem. 282, 3450-3457). We determined the mechanisms by which the composite PAP1 activity is regulated using rat and mouse hepatocytes. Levels of lipin-1A and -1B mRNA were increased by dexamethasone (a synthetic glucocorticoid) and this resulted in increased lipin-1 synthesis, protein levels and PAP1 activity. The stimulatory effect of dexamethasone on lipin-1 expression was enhanced by glucagon or cAMP and antagonized by insulin. Lipin-2 and lipin-3 mRNA were not increased by dexamethasone/cAMP, indicating that increased PAP1 activity is attributable specifically to enhanced lipin-1 expression. This work provides the first evidence for differential regulation of lipin activities. Selective lipin-1 expression explains the glucocorticoid and cAMP effects on increased hepatic PAP1 activity, which occurs in hepatic steatosis during starvation, diabetes, stress, and ethanol consumption.


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P. Zhang, L. O'Loughlin, D. N. Brindley, and K. Reue
Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis
J. Lipid Res., July 1, 2008; 49(7): 1519 - 1528.
[Abstract] [Full Text] [PDF]


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