HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Papers In Press, published online ahead of print November 1, 2006
J. Lipid Res., doi:10.1194/jlr.M600303-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M600303-JLR200v1 47/11/2503    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hanniman, E. A. Articles by Sinal, C. J. Search for Related Content PubMed PubMed Citation Articles by Hanniman, E. A. Articles by Sinal, C. J. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 2503-2514, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Apolipoprotein A-IV is regulated by nutritional and metabolic stress: involvement of glucocorticoids, HNF-4, and PGC-1

Elyhisha A. Hanniman^*, Gilles Lambert, Yusuke Inoue, Frank J. Gonzalez and Christopher J. Sinal^1,*

^* Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
University of Nantes Medical School, Institut National de la Santé et de la Recherche Médicale U539, Centre Hospitalier Universitaire de Nantes Hôtel Dieu, Nantes, France
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD

The online version of this article (available at http://www.jlr.org) contains additional two tables.

Published, JLR Papers in Press, August 23, 2006.

¹ To whom correspondence should be addressed. e-mail: csinal{at}dal.ca

Apolipoprotein A-IV (apoA-IV) is a 46 kDa glycoprotein that associates with triglyceride-rich and high density lipoproteins. Blood levels of apoA-IV generally correlate with triglyceride levels and are increased in diabetic patients. This study investigated the mechanisms regulating the in vivo expression of apoA-IV in the liver and intestine of mice in response to changes in nutritional status. Fasting markedly increased liver and ileal apoA-IV mRNA and plasma protein concentrations. This induction was associated with increased serum glucocorticoid levels and was abolished by adrenalectomy. Treatment with dexamethasone increased apoA-IV expression in adrenalectomized mice. Marked increases of apoA-IV expression were also observed in two murine models of diabetes. Reporter gene analysis of the murine and human apoA-IV/C-III promoters revealed a conserved cooperative activation by the hepatic nuclear factor-4 (HNF-4) and the peroxisome proliferator-activated receptor coactivator-1 (PGC-1) but no evidence of a direct regulatory role for the glucocorticoid receptor. Consistent with these in vitro data, induction of apoA-IV in response to fasting was accompanied by increases in HNF-4 and PGC-1 expression and was abolished in liver-specific HNF-4-deficient mice. Together, these results indicate that the induction of apoA-IV expression in fasting and diabetes likely involves PGC-1-mediated coactivation of HNF-4 in addition to glucocorticoid-dependent actions.

Supplementary key words glucocorticoid receptor • fasting • diabetes • adrenalectomy • hepatic nuclear factor-4 • peroxisome proliferator-activated receptor coactivator-1

Abbreviations: apoA-IV, apolipoprotein A-IV; Cyp, cytochrome P450; GR, glucocorticoid receptor; HNF, hepatic nuclear factor; HRE, hormone response element; PGC-1, peroxisome proliferator-activated receptor coactivator-1; PPAR, peroxisome proliferator-activated receptor; QPCR, real-time quantitative polymerase chain reaction; TBS-T, Tris-buffered saline plus Tween-20

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. G. Holloway, G. D. Miles, A. A. Dombkowski, and D. J. Waxman Liver-Specific Hepatocyte Nuclear Factor-4{alpha} Deficiency: Greater Impact on Gene Expression in Male than in Female Mouse Liver Mol. Endocrinol., May 1, 2008; 22(5): 1274 - 1286. [Abstract] [Full Text] [PDF]

				M. Hoekstra, I. Meurs, M. Koenders, R. Out, R. B. Hildebrand, J. K. Kruijt, M. Van Eck, and T. J. C. Van Berkel Absence of HDL cholesteryl ester uptake in mice via SR-BI impairs an adequate adrenal glucocorticoid-mediated stress response to fasting J. Lipid Res., April 1, 2008; 49(4): 738 - 745. [Abstract] [Full Text] [PDF]

				S. Leng, S. Lu, Y. Yao, Z. Kan, G. S. Morris, B. R. Stair, M. A. Cherny, and D. D. Black Hepatocyte nuclear factor-4 mediates apolipoprotein A-IV transcriptional regulation by fatty acid in newborn swine enterocytes Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G475 - G483. [Abstract] [Full Text] [PDF]