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

J. Biol. Chem., Vol. 282, Issue 46, 33553-33561, November 16, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/46/33553    most recent M706763200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Hessel, S. Articles by Wyss, A. Search for Related Content PubMed PubMed Citation Articles by Hessel, S. Articles by Wyss, A. Social Bookmarking                      What's this?

CMO1 Deficiency Abolishes Vitamin A Production from -Carotene and Alters Lipid Metabolism in Mice^*

Susanne Hessel¹, Anne Eichinger¹, Andrea Isken, Jaume Amengual², Silke Hunzelmann, Ulrich Hoeller, Volker Elste, Willi Hunziker^¶, Regina Goralczyk, Vitus Oberhauser, Johannes von Lintig³, and Adrian Wyss⁴

From the Institute of Biology I, Animal Physiology and Neurobiology, Hauptstrasse 1, D-79104 Freiburg, Germany, DSM Nutritional Products Ltd., R & D Human Nutrition and Health, P.O. Box 3255, CH-4002 Basel, Switzerland, and ^¶Frimorfo SA, Chemin du Musée, CH-1700 Fribourg, Switzerland

Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant-derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15'-oxygenase (CMO1) and a putative carotenoid-9',10'-oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing -carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in -carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1^-/- mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor -regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism.

Received for publication, August 14, 2007 , and in revised form, September 12, 2007.

^* This work was supported by a grant from the Ministry of Science and Art Baden-Württemberg (to J. v. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors contributed equally to this work.

² Supported by an exchange grant from the European Nutrigenomic Organization.

³ To whom correspondence may be addressed: Dept. of Neurobiology and Animal Physiology, Institute of Biology I, Hauptstrasse 1, Albert-Ludwig University, 79104 Freiburg, Germany. Tel.: 49-761-203-2539; Fax: 49-761-203-2921; E-mail: lintig{at}biologie.uni-freiburg.de. ⁴ To whom correspondence may be addressed: DSM Nutritional Products, 4303 Kaiseraugst, Switzerland. Tel.: 41-61-688-57-92; Fax: 41-61-688-16-40; E-mail: adrian.wyss{at}dsm.com.

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

This article has been cited by other articles:

				W. C. Leung, S. Hessel, C. Meplan, J. Flint, V. Oberhauser, F. Tourniaire, J. E. Hesketh, J. von Lintig, and G. Lietz Two common single nucleotide polymorphisms in the gene encoding {beta}-carotene 15,15'-monoxygenase alter {beta}-carotene metabolism in female volunteers FASEB J, April 1, 2009; 23(4): 1041 - 1053. [Abstract] [Full Text] [PDF]

				B. L. Lindshield, J. L. King, A. Wyss, R. Goralczyk, C.-H. Lu, N. A. Ford, and J. W. Erdman Jr Lycopene Biodistribution Is Altered in 15,15'-Carotenoid Monooxygenase Knockout Mice J. Nutr., December 1, 2008; 138(12): 2367 - 2371. [Abstract] [Full Text] [PDF]