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) All Versions of this Article: M400039-JLR200v1 45/9/1674    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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-H. Articles by Ntambi, J. M. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-H. Articles by Ntambi, J. M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 45, 1674-1682, September 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Lack of stearoyl-CoA desaturase 1 upregulates basal thermogenesis but causes hypothermia in a cold environment

Seong-Ho Lee^*, Agnieszka Dobrzyn^*, Pawel Dobrzyn^*, Shaikh Mizanoor Rahman^*, Makoto Miyazaki^* and James M. Ntambi^1,*,

^* Department of Biochemistry, University of Wisconsin, Madison, WI 53706
Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706

¹ To whom correspondence should be addressed. e-mail: ntambi{at}biochem.wisc.edu

Stearoyl-CoA desaturase (SCD) is a microsomal enzyme involved in the biosynthesis of oleate and palmitoleate. Mice with a targeted disruption of the SCD1 isoform (SCD1^–/–) exhibit reduced adiposity and increased energy expenditure. To address whether the energy expenditure is attributable to increased thermogenesis, we investigated the effect of SCD1 deficiency on basal and cold-induced thermogenesis. SCD1^–/– mice have increased expression of uncoupling proteins in brown adipose tissue (BAT) relative to controls. The ß3-adrenergic receptor (ß3-AR) expression was increased and the phosphorylation of cAMP response element binding protein and the protein level of peroxisome proliferator-activated receptor- coactivator-1 were increased in the SCD1^–/– mice. Both lipolysis and fatty acid oxidation were increased in the SCD1^–/– mice. When exposed to 4°C, SCD1^–/– mice showed hypothermia, hypoglycemia, and depleted liver glycogen. High levels of dietary oleate partially compensated for the hypothermia and rescued plasma glucose and liver glycogen.

These results suggest that SCD1 deficiency stimulates basal thermogenesis through the upregulation of the ß3-AR-mediated pathway and a subsequent increase in lipolysis and fatty acid oxidation in BAT. The hypothermia and hypoglycemia in cold-exposed SCD1^–/– mice and the compensatory recovery by oleate indicate an important role of SCD1 gene expression in thermoregulation.

Abbreviations: ß3-AR, ß3-adrenergic receptor; BAT, brown adipose tissue; CREB, cAMP response element binding protein; DAG, diacylglycerol; HSL, hormone-sensitive lipase; PCA, perchloric acid; PGC1, peroxisome proliferator-activated receptor- coactivator-1; PL, phospholipid; SCD, stearoyl-CoA desaturase; TG, triglyceride; UCP, uncoupling protein

Supplementary key words brown adipose tissue • uncoupling protein • lipid metabolism

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

This article has been cited by other articles:

				J. M. Brown, S. Chung, J. K. Sawyer, C. Degirolamo, H. M. Alger, T. Nguyen, X. Zhu, M.-N. Duong, A. L. Wibley, R. Shah, et al. Inhibition of Stearoyl-Coenzyme A Desaturase 1 Dissociates Insulin Resistance and Obesity From Atherosclerosis Circulation, September 30, 2008; 118(14): 1467 - 1475. [Abstract] [Full Text] [PDF]

				P. Dobrzyn, H. Sampath, A. Dobrzyn, M. Miyazaki, and J. M. Ntambi Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E357 - E364. [Abstract] [Full Text] [PDF]

				T. J. Brock, J. Browse, and J. L. Watts Fatty Acid Desaturation and the Regulation of Adiposity in Caenorhabditis elegans Genetics, June 1, 2007; 176(2): 865 - 875. [Abstract] [Full Text] [PDF]

				A. Dobrzyn, P. Dobrzyn, S.-H. Lee, M. Miyazaki, P. Cohen, E. Asilmaz, D. G. Hardie, J. M. Friedman, and J. M. Ntambi Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing {beta}-oxidation in skeletal muscle Am J Physiol Endocrinol Metab, March 1, 2005; 288(3): E599 - E607. [Abstract] [Full Text] [PDF]