This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gowri, P. M. Articles by Katzenellenbogen, B. S. Search for Related Content PubMed PubMed Citation Articles by Gowri, P. M. Articles by Katzenellenbogen, B. S.

Lipin1 Regulation by Estrogen in Uterus and Liver: Implications for Diabetes and Fertility

Departments of Molecular and Integrative Physiology (P.M.G., S.S., B.S.K.) and Cell and Developmental Biology (B.S.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; and Department of Pediatrics (S.B.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

Address all correspondence and requests for reprints to: Dr. Benita S. Katzenellenbogen, University of Illinois, Department of Molecular and Integrative Physiology, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801-3704. E-mail: katzenel{at}uiuc.edu.

Estrogens are essential for fertility and also have important effects on regulation of adiposity and the euglycemic state. We report here that lipin1, a candidate gene for lipodystrophy and obesity that is a phosphatidic acid phosphatase critical in regulation of cellular levels of diacylglycerol and triacylglycerol and a key regulator of lipid utilization, is rapidly and robustly down-regulated in the uterus by estradiol via the estrogen receptor. Lipin1 is expressed predominantly in the uterine luminal and glandular epithelium, and during the estrous cycle, lipin1 is lowest when blood levels of estrogen are highest. Lipin1 is expressed throughout all cells in the liver of ovariectomized female mice, and a sustained down-regulation is observed at the mRNA, protein and immunohistochemical levels after estrogen administration. Because the coupling of proper energy use and availability is central to reproduction, we also investigated expression of lipin1 in the uterus and liver of several mouse models of diabetes. Nonobese diabetic (NOD) mice, which have high blood levels of estrogen and impaired fertility, were severely deficient in lipin1 in the uterus and liver, which, interestingly, could be restored by insulin treatment. By contrast, nonobese diabetic/severe combined immunodeficient (NOD-SCID) mice, which do not develop diabetes, showed normal levels of lipin1. Our findings of lipin1 regulation by estrogen in two key target organs suggest a new role for this lipid-regulating phosphatase not only in central metabolic regulation but also in uterine function and reproductive biology. Estrogen regulation of lipin1 may provide a mechanistic link between estrogens, lipid metabolism, and lipid signaling.

This article has been cited by other articles:

				G. M. Carman and G.-S. Han Phosphatidic Acid Phosphatase, a Key Enzyme in the Regulation of Lipid Synthesis J. Biol. Chem., January 30, 2009; 284(5): 2593 - 2597. [Full Text] [PDF]

				K. Reue and D. N. Brindley Thematic Review Series: Glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism J. Lipid Res., December 1, 2008; 49(12): 2493 - 2503. [Abstract] [Full Text] [PDF]

				M. C. Vantyghem, D. Vincent-Desplanques, F. Defrance-Faivre, J. Capeau, C. Fermon, A. S. Valat, O. Lascols, A. C. Hecart, P. Pigny, B. Delemer, et al. Fertility and Obstetrical Complications in Women with LMNA-Related Familial Partial Lipodystrophy J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2223 - 2229. [Abstract] [Full Text] [PDF]