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

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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Feingold, K. Articles by Grunfeld, C. Search for Related Content PubMed PubMed Citation Articles by Feingold, K. Articles by Grunfeld, C.

Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response

Metabolism Section, Department of Medicine, University of California San Francisco, Medical Service, Department of Veterans Affairs Medical Center, San Francisco, California 94121

Submitted 7 May 2003 ; accepted in final form 27 September 2003

Severe sepsis results in the decreased uptake and oxidation of fatty acids in the heart and cardiac failure. Some of the key proteins required for fatty acid uptake and oxidation in the heart have been shown to be downregulated after endotoxin (LPS) administration. The nuclear hormone receptors, peroxisome proliferator-activated receptor (PPAR) and thyroid receptor (TR), which heterodimerize with the retinoid X receptor (RXR), are important regulators of fatty acid metabolism and decrease in the liver after LPS administration. In the present study, we demonstrate that LPS treatment produces a rapid and marked decrease in the mRNA levels of all three RXR isoforms, PPAR and PPAR, and TR and TR in the heart. Moreover, LPS administration also decreased the expression of the coactivators CREB-binding protein (CBP)/p300, steroid receptor coactivator (SRC)-1, SRC-3, TR-associated protein (TRAP)220, and PPAR coactivator (PGC)-1, all of which are required for the transcriptional activity of RXR-PPAR and RXR-TR. In addition, the mRNA levels of the target genes malic enzyme, Spot 14, sarcoplasmic reticulum Ca²⁺-ATPase, or SERCA2, the VLDL receptor, fatty acyl-CoA synthetase, fatty acid transporter/CD36, carnitine palmitoyltransferase I, and lipoprotein lipase decrease in the heart after LPS treatment. The decrease in expression of RXR, -, and -, PPAR and -, and TR and -, and of the coactivators CBP/p300, SRC-1, SRC-3, TRAP220, and PGC-1 and the genes they regulate, induced by LPS in the heart, could account for the decreased expression of key proteins required for fatty acid oxidation and thereby play an important role in cardiac contractility. These alterations could contribute to the myocardial dysfunction that occurs during sepsis.

endotoxin; fatty acid oxidation; cardiac contractility

This article has been cited by other articles:

				K. R. Feingold, Y. Wang, A. Moser, J. K. Shigenaga, and C. Grunfeld LPS decreases fatty acid oxidation and nuclear hormone receptors in the kidney J. Lipid Res., October 1, 2008; 49(10): 2179 - 2187. [Abstract] [Full Text] [PDF]

				B. Lu, A. H. Moser, J. K. Shigenaga, K. R. Feingold, and C. Grunfeld Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response J. Lipid Res., October 1, 2006; 47(10): 2179 - 2190. [Abstract] [Full Text] [PDF]

				H.-L. Noh, K. Okajima, J. D. Molkentin, S. Homma, and I. J. Goldberg Acute lipoprotein lipase deletion in adult mice leads to dyslipidemia and cardiac dysfunction Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E755 - E760. [Abstract] [Full Text] [PDF]

				C. J. Cifelli and A. C. Ross All-trans-retinoic acid distribution and metabolism in vitamin A-marginal rats. Am J Physiol Gastrointest Liver Physiol, August 1, 2006; 291(2): G195 - G202. [Abstract] [Full Text] [PDF]

				Y. Wang, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Downregulation of liver X receptor-{alpha} in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines J. Lipid Res., November 1, 2005; 46(11): 2377 - 2387. [Abstract] [Full Text] [PDF]

				M. S. Kim, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Suppression of estrogen-related receptor {alpha} and medium-chain acyl-coenzyme A dehydrogenase in the acute-phase response J. Lipid Res., October 1, 2005; 46(10): 2282 - 2288. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]