FASEB J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published as doi: 10.1096/fj.06-7964com.
 (The FASEB Journal. 2007;21:2886-2896.)
© 2007 FASEB
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
fj.06-7964comv1
21/11/2886    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, M.
Right arrow Articles by Napoli, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, M.
Right arrow Articles by Napoli, J. L.

Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse

Min Zhang1,2, Peirong Hu1, Charles R. Krois, Maureen A. Kane and Joseph L. Napoli3

Nutritional Science and Toxicology, University of California, Berkeley, California, USA

3Correspondence: Nutritional Science and Toxicology, 119 Morgan Hall, MC#3104, University of California, Berkeley, CA 94720-3104, USA. Email: jna{at}berkeley.edu

Rat RoDH performs efficiently (Vm/Km) in a pathway of all-trans-retinoic acid biosynthesis in cells and recognizes the physiological form of vitamin A, i.e., retinol bound with cellular retinol binding-protein, type I. Here we report that mouse embryo (e7.5 to e18.5) and liver (e12.5 to P2M) display inversely related mRNA expression of an Rodh ortholog, rdh1, and a major retinoic acid catabolic enzyme, cyp26a1, suggesting coordinate modulation of retinoic acid homeostasis. Rdh1 inactivation by homologous recombination produces mice with decreased liver cyp26a1 mRNA and protein and increased liver and kidney retinoid stores, when fed vitamin A-restricted diets. Thus, null mice autocompensate by down-regulating cyp26a1 and sparing retinoids, indicating that rdh1 metabolizes retinoids in vivo. Surprisingly, rdh1-null mice grow longer than wild type, with increased weight and adiposity, when restricted in vitamin A. Liver, kidney, and multiple fat pads increase in weight. Some differences reflect the larger sizes of rdh1-null mice, but mesentery, femoral, and inguinal fat pads grow disproportionately larger. These data reveal an unexpected contribution of Rdh1 to size and adiposity and provide the first genetic evidence of a candidate retinol dehydrogenase affecting either vitamin A-related homeostasis physiologically or vitamin A-related gene expression or biological function in vivo.—Zhang, M., Hu, P., Krois, C. R., Kane, M. A., Napoli, J. L. Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse.


Key Words: retinoic acid • retinol • short-chain dehydrogenase/reductase




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
O. V. Belyaeva, M. P. Johnson, and N. Y. Kedishvili
Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase
J. Biol. Chem., July 18, 2008; 283(29): 20299 - 20308.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by The Federation of American Societies for Experimental Biology.