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

Papers In Press, published online ahead of print April 1, 2006
J. Lipid Res., doi:10.1194/jlr.M500553-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M500553-JLR200v1 47/4/745    most recent 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vergnes, L. Articles by Reue, K. Search for Related Content PubMed PubMed Citation Articles by Vergnes, L. Articles by Reue, K. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 745-754, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity

Laurent Vergnes^*, Anne P. Beigneux, Ryan Davis, Steven M. Watkins, Stephen G. Young and Karen Reue^1,*

^* Departments of Medicine and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, and VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073
Division of Cardiology, Department of Internal Medicine, University of California, Los Angeles, CA 90095
Lipomics Technologies, West Sacramento, CA 95691

The online version of this article (available at http://www.jlr.org) contains additional table and figure.

Published, JLR Papers in Press, January 25, 2006.

¹ To whom correspondence should be addressed. e-mail: reuek{at}ucla.edu

Triglyceride synthesis in most mammalian tissues involves the sequential addition of fatty acids to a glycerol backbone, with unique enzymes required to catalyze each acylation step. Acylation at the sn-2 position requires 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) activity. To date, seven Agpat genes have been identified based on activity and/or sequence similarity, but their physiological functions have not been well established. We have generated a mouse model deficient in AGPAT6, which is normally expressed at high levels in brown adipose tissue (BAT), white adipose tissue (WAT), and liver. Agpat6-deficient mice exhibit a 25% reduction in body weight and resistance to both diet-induced and genetically induced obesity. The reduced body weight is associated with increased energy expenditure, reduced triglyceride accumulation in BAT and WAT, reduced white adipocyte size, and lack of adipose tissue in the subdermal region. In addition, the fatty acid composition of triacylglycerol, diacylglycerol, and phospholipid is altered, with proportionally greater polyunsaturated fatty acids at the expense of monounsaturated fatty acids. Thus, Agpat6 plays a unique role in determining triglyceride content and composition in adipose tissue and liver that cannot be compensated by other members of the Agpat family.

Supplementary key words acyltransferase • gene-trap • adipose tissue • energy expenditure • 1-acylglycerol-3-phosphate O-acyltransferase

Abbreviations: AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; BAT, brown adipose tissue; DAG, diacylglycerol; DGAT1, acyl-coenzyme A:diacylglycerol acyltransferase-1; GPAT, glycerol-3-phosphate acyltransferase; HF/HC, high-fat/high-carbohydrate; TAG, triacylglycerol; WAT, white adipose tissue

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

This article has been cited by other articles:

				S. Sukumaran, R. I Barnes, A. Garg, and A. K Agarwal Functional characterization of the human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 10/glycerol-3-phosphate acyltransferase isoform 3 J. Mol. Endocrinol., June 1, 2009; 42(6): 469 - 478. [Abstract] [Full Text] [PDF]

				K. Takeuchi and K. Reue Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1195 - E1209. [Abstract] [Full Text] [PDF]

				R. E. Gimeno and J. Cao Thematic Review Series: Glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity J. Lipid Res., October 1, 2008; 49(10): 2079 - 2088. [Abstract] [Full Text] [PDF]

				M. Bionaz and J. J. Loor ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 Are the Most Abundant Isoforms in Bovine Mammary Tissue and Their Expression Is Affected by Stage of Lactation J. Nutr., June 1, 2008; 138(6): 1019 - 1024. [Abstract] [Full Text] [PDF]

				Y. Q. Chen, M.-S. Kuo, S. Li, H. H. Bui, D. A. Peake, P. E. Sanders, S. J. Thibodeaux, S. Chu, Y.-W. Qian, Y. Zhao, et al. AGPAT6 Is a Novel Microsomal Glycerol-3-phosphate Acyltransferase J. Biol. Chem., April 11, 2008; 283(15): 10048 - 10057. [Abstract] [Full Text] [PDF]

				C. A. Nagle, L. Vergnes, H. DeJong, S. Wang, T. M. Lewin, K. Reue, and R. A. Coleman Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6-/- mice J. Lipid Res., April 1, 2008; 49(4): 823 - 831. [Abstract] [Full Text] [PDF]

				F. F. Chehab Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect? Endocrinology, March 1, 2008; 149(3): 925 - 934. [Abstract] [Full Text] [PDF]

				R. A. Hegele, T. R. Joy, S. A. Al-Attar, and B. K. Rutt Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism J. Lipid Res., July 1, 2007; 48(7): 1433 - 1444. [Abstract] [Full Text] [PDF]

				A. K Agarwal, S. Sukumaran, R. Bartz, R. I Barnes, and A. Garg Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9: cloning, tissue distribution, gene structure, and enzymatic activity J. Endocrinol., June 1, 2007; 193(3): 445 - 457. [Abstract] [Full Text] [PDF]

				J. Cao, J.-L. Li, D. Li, J. F. Tobin, and R. E. Gimeno Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis PNAS, December 26, 2006; 103(52): 19695 - 19700. [Abstract] [Full Text] [PDF]

				A. J. Lusis A thematic review series: systems biology approaches to metabolic and cardiovascular disorders J. Lipid Res., September 1, 2006; 47(9): 1887 - 1890. [Full Text] [PDF]

				K. Reue and L. Vergnes Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Approaches to lipid metabolism gene identification and characterization in the postgenomic era J. Lipid Res., September 1, 2006; 47(9): 1891 - 1907. [Abstract] [Full Text] [PDF]

				A. P. Beigneux, L. Vergnes, X. Qiao, S. Quatela, R. Davis, S. M. Watkins, R. A. Coleman, R. L. Walzem, M. Philips, K. Reue, et al. Agpat6--a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium J. Lipid Res., April 1, 2006; 47(4): 734 - 744. [Abstract] [Full Text] [PDF]