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) An erratum has been published All Versions of this Article: M600177-JLR200v1 47/9/2028    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services 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 Wang, Y. Articles by Jump, D. B. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Jump, D. B. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 2028-2041, September 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity

Yun Wang^*,1, Daniela Botolin^*,1, Jinghua Xu^,1, Barbara Christian^*, Ernestine Mitchell^*, Bolleddula Jayaprakasam, Muraleedharan Nair, Jeffery M. Peters^**, Julia Busik^*, L. Karl Olson^* and Donald B. Jump^2,*,

^* Department of Physiology, Michigan State University, East Lansing, MI 48824
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824
Department of Horticulture, Michigan State University, East Lansing, MI 48824
^** Department of Veterinary Science and Biomedical Sciences, Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, PA 16802

Published, JLR Papers in Press, June 21, 2006.

¹ Yun Wang, Daniela Botolin, and Jinghua Xu contributed equally to this work.

² To whom correspondence should be addressed. e-mail: jump{at}msu.edu

Fatty acid elongases and desaturases play an important role in hepatic and whole body lipid composition. We examined the role that key transcription factors played in the control of hepatic elongase and desaturase expression. Studies with peroxisome proliferator-activated receptor (PPAR)-deficient mice establish that PPAR was required for WY14643-mediated induction of fatty acid elongase-5 (Elovl-5), Elovl-6, and all three desaturases [⁵ desaturase (⁵D), ⁶D, and ⁹D]. Increased nuclear sterol-regulatory element binding protein-1 (SREBP-1) correlated with enhanced expression of Elovl-6, ⁵D, ⁶D, and ⁹D. Only ⁹D was also regulated independently by liver X receptor (LXR) agonist. Glucose induction of L-type pyruvate kinase, ⁹D, and Elovl-6 expression required the carbohydrate-regulatory element binding protein/MAX-like factor X (ChREBP/MLX) heterodimer. Suppression of Elovl-6 and ⁹D expression in livers of streptozotocin-induced diabetic rats and high fat-fed glucose-intolerant mice correlated with low levels of nuclear SREBP-1. In leptin-deficient obese mice (Lep^ob/ob), increased SREBP-1 and MLX nuclear content correlated with the induction of Elovl-5, Elovl-6, and ⁹D expression and the massive accumulation of monounsaturated fatty acids (18:1,n-7 and 18:1,n-9) in neutral lipids. Diabetes- and obesity-induced changes in hepatic lipid composition correlated with changes in elongase and desaturase expression. In conclusion, these studies establish a role for PPAR, LXR, SREBP-1, ChREBP, and MLX in the control of hepatic fatty acid elongase and desaturase expression and lipid composition.

Supplementary key words peroxisome proliferator-activated receptor • sterol-regulatory element binding protein-1 • carbohydrate-regulatory element binding protein • MAX-like factor X • liver X receptor

Abbreviations: ACC, acetyl-coenzyme A carboxylase; ChoRE, carbohydrate-regulatory element; ChREBP, carbohydrate-regulatory element binding protein; ⁵D, ⁵ desaturase; Elovl-1, fatty acid elongase-1; HNF-4, hepatic nuclear factor-4; L-PK, L-type pyruvate kinase; Luc, luciferase; LXR, liver X receptor; MLX, MAX-like factor X; PPAR, peroxisome proliferator-activated receptor ; qRT, quantitative real-time; SREBP-1, sterol-regulatory element binding protein-1; T1317, T0901317; T₃, triiodothyronine

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

This article has been cited by other articles:

				M. Igarashi, K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport Rat heart cannot synthesize docosahexaenoic acid from circulating {alpha}-linolenic acid because it lacks elongase-2 J. Lipid Res., August 1, 2008; 49(8): 1735 - 1745. [Abstract] [Full Text] [PDF]

				Y. Wang, M. Torres-Gonzalez, S. Tripathy, D. Botolin, B. Christian, and D. B. Jump Elevated hepatic fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition J. Lipid Res., July 1, 2008; 49(7): 1538 - 1552. [Abstract] [Full Text] [PDF]

				M. Igarashi, K. Ma, L. Chang, J. M. Bell, and S. I. Rapoport Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain J. Lipid Res., November 1, 2007; 48(11): 2463 - 2470. [Abstract] [Full Text] [PDF]