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

J. Biol. Chem., Vol. 279, Issue 28, 29031-29042, July 9, 2004

This Article Full Text Full Text (PDF) An addition or correction has been published All Versions of this Article: 279/28/29031    most recent M309449200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nagata, R. Articles by Kashiwagi, A. Search for Related Content PubMed PubMed Citation Articles by Nagata, R. Articles by Kashiwagi, A. Social Bookmarking                      What's this?

Single Nucleotide Polymorphism (–468 Gly to Ala) at the Promoter Region of Sterol Regulatory Element-binding Protein-1c Associates with Genetic Defect of Fructose-induced Hepatic Lipogenesis^*

Ryoko Nagata, Yoshihiko Nishio, Osamu Sekine, Yoshio Nagai, Yasuhiro Maeno, Satoshi Ugi, Hiroshi Maegawa, and Atsunori Kashiwagi

From the Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga, 520-2192, Japan

To evaluate the genetic susceptibility to metabolic disorders induced by high fructose diet, we investigated the metabolic characteristics in 10 strains of inbred mice and found that they were separated into CBA and DBA groups according to the response to high fructose diet. The hepatic mRNA expression of the sterol regulatory element-binding protein-1 (SREBP-1) in CBA/JN was remarkably enhanced by high fructose diet but not in DBA/2N. Similar results were observed in primary hepatocytes after exposure to fructose. The nucleotide sequence at –468 bp from the putative starting point of the SREBP-1c gene was adenine in the DBA group while it was guanine in the CBA group. In hepatocytes from CBA/JN, the activity of CBA-SREBP-1c promoter was significantly increased by 2.4- and 2.2-fold, in response to 30 mM fructose or 10 nM insulin, respectively, whereas the activity of DBA-SREBP-1c promoter responded to insulin but not to fructose. In hepatocytes from DBA/2N, both types of SREBP-1c promoter activities in response to insulin were attenuated. Furthermore, electrophoretic mobility shift assay revealed an unidentified nuclear protein bound to the oligonucleotides made from the region between –453 to –480 bp of the SREBP-1c promoter of CBA/JN but not to the probe from DBA/2N. Thus, in DBA/2N, the reduced mRNA expression of SREBP-1 after fructose refeeding appeared to associate with two independent mechanisms, 1) loss of binding of unidentified proteins to the region between –453 to –480 bp of the SREBP-1c promoter and 2) impaired insulin stimulation of SREBP-1c promoter activity.

Received for publication, August 26, 2003 , and in revised form, April 30, 2004.

^* This study was supported in part by the Suzuken Memorial Foundation. 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.

To whom correspondence should be addressed. Tel.: 81-77-548-2222; Fax: 81-77-543-3858; E-mail: nishio{at}belle.shiga-med.ac.jp.

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

This article has been cited by other articles:

				S. H Zeisel Nutrigenomics and metabolomics will change clinical nutrition and public health practice: insights from studies on dietary requirements for choline Am. J. Clinical Nutrition, September 1, 2007; 86(3): 542 - 548. [Abstract] [Full Text] [PDF]

				V. Farah, K. M. Elased, and M. Morris Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1083 - H1089. [Abstract] [Full Text] [PDF]