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 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 Hunt, M. C. Articles by Alexson, S. E. H. Search for Related Content PubMed PubMed Citation Articles by Hunt, M. C. Articles by Alexson, S. E. H. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 814-823, May 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Involvement of the peroxisome proliferator-activated receptor in regulating long-chain acyl-CoA thioesterases

Correspondence to: Stefan E. H. Alexson

Long-chain acyl-CoA thioesterases catalyze the hydrolysis of acyl-CoAs to the corresponding free fatty acid and CoA. We recently cloned four members of a novel multi-gene family of peroxisome proliferator-induced genes encoding cytosolic (CTE-I), mitochondrial (MTE-I), and peroxisomal (PTE-Ia and PTE-Ib) acyl-CoA thioesterases (Hunt et al. 1999. J. Biol. Chem. 274: 34317–34326). As the peroxisome proliferator-activated receptor alpha (PPAR) plays a central role in regulating genes involved in lipid metabolism, we examined the involvement of this receptor in regulation of the thioesterases, particularly CTE-I and MTE-I. Northern blot analysis shows that the induction of these thioesterases by clofibrate is mediated through a strictly PPAR-dependent mechanism. All four acyl-CoA thioesterases are induced at mRNA level by fasting and using PPAR-null mice, it is evident that the increase in CTE-I due to fasting is mainly independent of the PPAR in liver and heart. The CTE-I gene responds rapidly to fasting, with induction of mRNA and protein evident after 6 h. This fasting effect is rapidly reversible, with CTE-I mRNA returning almost to control levels after 3 h refeeding, and being further repressed to 20% of control after 9 h refeeding. Although CTE-I mRNA shows a low basal expression in liver, it can be suppressed 90% by feeding a fat-free diet.

These data demonstrate that the nutritional regulation of the thioesterases involves the PPAR and other signaling pathways responsible for activation and repression. Putative physiological functions for the acyl-CoA thioesterases are discussed.—Hunt, M. C., P. J. G. Lindquist, J. M. Peters, F. J. Gonzalez, U. Diczfalusy, and S. E. H. Alexson. Involvement of the peroxisome proliferator-activated receptor in regulating long-chain acyl-CoA thioesterases. J. Lipid Res. 2000. 41: 814;–823.

Supplementary key words: acyl-CoA thioesterases, acyl-CoA, fasting, peroxisome proliferator-activated receptor, lipid metabolism, fat free diet, clofibrate

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

This article has been cited by other articles:

				M. A. K. Westin, M. C. Hunt, and S. E. H. Alexson Peroxisomes Contain a Specific Phytanoyl-CoA/Pristanoyl-CoA Thioesterase Acting as a Novel Auxiliary Enzyme in {alpha}- and beta-Oxidation of Methyl-branched Fatty Acids in Mouse J. Biol. Chem., September 14, 2007; 282(37): 26707 - 26716. [Abstract] [Full Text] [PDF]

				B. Dongol, Y. Shah, I. Kim, F. J. Gonzalez, and M. C. Hunt The acyl-CoA thioesterase I is regulated by PPAR{alpha} and HNF4{alpha} via a distal response element in the promoter J. Lipid Res., August 1, 2007; 48(8): 1781 - 1791. [Abstract] [Full Text] [PDF]

				L. K. Gerber, B. J. Aronow, and M. A. Matlib Activation of a novel long-chain free fatty acid generation and export system in mitochondria of diabetic rat hearts Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1198 - C1207. [Abstract] [Full Text] [PDF]

				J. M. Dhahbi, T. Tsuchiya, H.-J. Kim, P. L. Mote, and S. R. Spindler Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2006; 61(3): 218 - 231. [Abstract] [Full Text] [PDF]

				M. A. K. Westin, M. C. Hunt, and S. E. H. Alexson The Identification of a Succinyl-CoA Thioesterase Suggests a Novel Pathway for Succinate Production in Peroxisomes J. Biol. Chem., November 18, 2005; 280(46): 38125 - 38132. [Abstract] [Full Text] [PDF]

				K. Solaas, B. F. Kase, V. Pham, K. Bamberg, M. C. Hunt, and S. E. H. Alexson Differential regulation of cytosolic and peroxisomal bile acid amidation by PPAR{alpha} activation favors the formation of unconjugated bile acids J. Lipid Res., June 1, 2004; 45(6): 1051 - 1060. [Abstract] [Full Text] [PDF]

				M. A. K. Westin, S. E. H. Alexson, and M. C. Hunt Molecular Cloning and Characterization of Two Mouse Peroxisome Proliferator-activated Receptor {alpha} (PPAR{alpha})-regulated Peroxisomal Acyl-CoA Thioesterases J. Biol. Chem., May 21, 2004; 279(21): 21841 - 21848. [Abstract] [Full Text] [PDF]

				G. B. Tilton, J. M. Shockey, and J. Browse Biochemical and Molecular Characterization of ACH2, an Acyl-CoA Thioesterase from Arabidopsis thaliana J. Biol. Chem., February 27, 2004; 279(9): 7487 - 7494. [Abstract] [Full Text] [PDF]

				A. Cabrero, M. Merlos, J. C. Laguna, and M. V. Carrera Down-regulation of acyl-CoA oxidase gene expression and increased NF-{kappa}B activity in etomoxir-induced cardiac hypertrophy J. Lipid Res., February 1, 2003; 44(2): 388 - 398. [Abstract] [Full Text] [PDF]

				K. Huhtinen, J. O'Byrne, P. J. G. Lindquist, J. A. Contreras, and S. E. H. Alexson The Peroxisome Proliferator-induced Cytosolic Type I Acyl-CoA Thioesterase (CTE-I) Is a Serine-Histidine-Aspartic Acid alpha /beta Hydrolase J. Biol. Chem., January 25, 2002; 277(5): 3424 - 3432. [Abstract] [Full Text] [PDF]

				T. E. Akiyama, C. J. Nicol, C. Fievet, B. Staels, J. M. Ward, J. Auwerx, S. S. T. Lee, F. J. Gonzalez, and J. M. Peters Peroxisome Proliferator-activated Receptor-alpha Regulates Lipid Homeostasis, but Is Not Associated with Obesity. STUDIES WITH CONGENIC MOUSE LINES J. Biol. Chem., October 12, 2001; 276(42): 39088 - 39093. [Abstract] [Full Text] [PDF]

				M. C. Hunt, Y.-Z. Yang, G. Eggertsen, C. M. Carneheim, M. Gafvels, C. Einarsson, and S. E. H. Alexson The Peroxisome Proliferator-activated Receptor alpha (PPARalpha ) Regulates Bile Acid Biosynthesis J. Biol. Chem., September 8, 2000; 275(37): 28947 - 28953. [Abstract] [Full Text] [PDF]

				M. C. Hunt, K. Solaas, B. F. Kase, and S. E. H. Alexson Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism J. Biol. Chem., January 4, 2002; 277(2): 1128 - 1138. [Abstract] [Full Text] [PDF]