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: 288/3/E599    most recent 00439.2004v1 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 ISI Web of Science 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 ISI Web of Science (25) Citing Articles via Google Scholar Google Scholar Articles by Dobrzyn, A. Articles by Ntambi, J. M. Search for Related Content PubMed PubMed Citation Articles by Dobrzyn, A. Articles by Ntambi, J. M.

Stearoyl-CoA desaturase-1 deficiency reduces ceramide synthesis by downregulating serine palmitoyltransferase and increasing -oxidation in skeletal muscle

Departments of ¹Biochemistry and ⁵Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin; ²Laboratory of Molecular Genetics and ⁴Howard Hughes Medical Institute, The Rockefeller University, New York, New York; and ³Division of Molecular Physiology, School of Life Sciences, Dundee University, Dundee, United Kingdom

Submitted 15 September 2004 ; accepted in final form 15 November 2004

Stearoyl-CoA desaturase (SCD) has recently been shown to be a critical control point of lipid partitioning and body weight regulation. Lack of SCD1 function significantly increases insulin sensitivity in skeletal muscles and corrects the hypometabolic phenotype of leptin-deficient ob/ob mice, indicating the direct antilipotoxic action of SCD1 deficiency. The mechanism underlying the metabolic effects of SCD1 mutation is currently unknown. Here we show that SCD1 deficiency reduced the total ceramide content in oxidative skeletal muscles (soleus and red gastrocnemius) by 40%. The mRNA levels and activity of serine palmitoyltransferase (SPT), a key enzyme in ceramide synthesis, as well as the incorporation of [¹⁴C]palmitate into ceramide were decreased by 50% in red muscles of SCD1^–/– mice. The content of fatty acyl-CoAs, which contribute to de novo ceramide synthesis, was also reduced. The activity and mRNA levels of carnitine palmitoyltransferase I (CPT I) and the rate of -oxidation were increased in oxidative muscles of SCD1^–/– mice. Furthermore, SCD1 deficiency increased phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK activation may be partially responsible for the increased fatty acid oxidation and decreased ceramide synthesis in red muscles of SCD1^–/– mice. SCD1 deficiency also reduced SPT activity and ceramide content and increased AMPK phosphorylation and CPT I activity in muscles of ob/ob mice. Taken together, these results indicate that SCD1 deficiency reduces ceramide synthesis by decreasing SPT expression and increasing the rate of -oxidation in oxidative muscles.

adenosine 5'-monophosphate-activated protein kinase; ob/ob mouse; leptin; carnitine palmitoyltransferase

This article has been cited by other articles:

				R. Mar-Heyming, M. Miyazaki, D. Weissglas-Volkov, N. A. Kolaitis, N. Sadaat, C. Plaisier, P. Pajukanta, R. M. Cantor, T. W.A. de Bruin, J. M. Ntambi, et al. Association of Stearoyl-CoA Desaturase 1 Activity With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1193 - 1199. [Abstract] [Full Text] [PDF]

				C. Roy, S. Paglialunga, A. Fisette, P. Schrauwen, E. Moonen-Kornips, J. St-Onge, M. K. Hesselink, D. Richard, D. R. Joanisse, and K. Cianflone Shift in metabolic fuel in acylation-stimulating protein-deficient mice following a high-fat diet Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1051 - E1059. [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]

				M. C. Levin, M. Monetti, M. J. Watt, M. P. Sajan, R. D. Stevens, J. R. Bain, C. B. Newgard, R. V. Farese Sr., and R. V. Farese Jr. Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1772 - E1781. [Abstract] [Full Text] [PDF]

				A. C. Smith, K. L. Mullen, K. A. Junkin, J. Nickerson, A. Chabowski, A. Bonen, and D. J. Dyck Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia Am J Physiol Endocrinol Metab, July 1, 2007; 293(1): E172 - E181. [Abstract] [Full Text] [PDF]

				J. C. Molero, N. Turner, C. B.F. Thien, W. Y. Langdon, D. E. James, and G. J. Cooney Genetic Ablation of the c-Cbl Ubiquitin Ligase Domain Results in Increased Energy Expenditure and Improved Insulin Action Diabetes, December 1, 2006; 55(12): 3411 - 3417. [Abstract] [Full Text] [PDF]

				S. A. Lehnert, K. A. Byrne, A. Reverter, G. S. Nattrass, P. L. Greenwood, Y. H. Wang, N. J. Hudson, and G. S. Harper Gene expression profiling of bovine skeletal muscle in response to and during recovery from chronic and severe undernutrition J Anim Sci, December 1, 2006; 84(12): 3239 - 3250. [Abstract] [Full Text] [PDF]

				D. Mainieri, S. Summermatter, J. Seydoux, J.-P. Montani, S. Rusconi, A. P. Russell, O. Boss, A. J. Buchala, and A. G. Dulloo A role for skeletal muscle stearoyl-CoA desaturase 1 in control of thermogenesis FASEB J, August 1, 2006; 20(10): 1751 - 1753. [Abstract] [Full Text] [PDF]

				A. K. Busch, E. Gurisik, D. V. Cordery, M. Sudlow, G. S. Denyer, D. R. Laybutt, W. E. Hughes, and T. J. Biden Increased Fatty Acid Desaturation and Enhanced Expression of Stearoyl Coenzyme A Desaturase Protects Pancreatic {beta}-Cells from Lipoapoptosis Diabetes, October 1, 2005; 54(10): 2917 - 2924. [Abstract] [Full Text] [PDF]