- Acyltransferase, Triglyceride, Lipid droplet, Obesity, Diabetes
About Dr. Scot Stone
B.Sc. University of Saskatchewan, 1993, Department of Physiology
The goal of my research program is to understand how DGAT2 functions in cells to synthesize triacylglycerol. Triacylglycerols are the major storage form of energy in eukaryotic organisms. However, excessive accumulation of triacylglycerols in adipose tissue results in obesity, which has now reached epidemic proportions in Canada. In addition, excessive levels of triacylglycerols in non-adipose tissues, such as skeletal muscle, liver, heart, and pancreatic beta cells are associated with insulin resistance and can lead to type 2 diabetes mellitus, while elevated plasma triacylglycerol levels are associated with cardiovascular disease.
In mammals, triacylglycerols are synthesized in a reaction catalyzed by acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes (DGAT1 and DGAT2) and are stored primarily in white adipose tissue in cytosolic lipid droplets. DGAT2 is present in the endoplasmic reticulum, but also interacts with lipid droplets where it catalyzes triacylglycerol synthesis for lipid droplet expansion.
Our studies are designed to address fundamental questions in triacylglycerol metabolism and provide new insights into the molecular mechanisms responsible for triacylglycerol synthesis and storage. In the long term, this knowledge may be of clinical significance with respect to the development of therapies for the treatment or prevention of obesity and cardiovascular disease.
- 2014 Jin Y, McFie PJ, Banman SL, Brandt C, Stone SJ. Diacylglycerol acyltransferase-2 (DGAT2) and monoacylglycerol acyltransferase-2 (MGAT2) interact to promote triacylglycerol synthesis. J Biol Chem. 2014 Oct 10;289(41):28237-48.
- 2014 McFie PJ, Jin Y, Banman SL, Beauchamp E, Berthiaume LG, Stone SJ. Characterization of the interaction of diacylglycerol acyltransferase-2 with the endoplasmic reticulum and lipid droplets. Biochim Biophys Acta. 2014 Sep;1841(9):1318-28.
- 2011 Stone, S.J. Mammalian Diacylglycerol Acyltransferase Enzymes. TheLipid Library (http://lipidlibrary.aocs.org/animbio/dgat/index.htm)
- 2011 Qin, W., Sundaram, M., Wang, Y., Zhou, H.,Zhong, S., Chang, C., Manhas, S., Yao, E.F., Parks, R.J., McFie, P.J., Stone, S.J., Jiang, Z.G., Wang, C.,Figeys, D., Jia, W. and Yao, Z. Missense mutation in APOC3 within theC-terminal lipid-binding domain of human apoC-III results in impaired assemblyand secretion of triacylglycerol-rich very low density lipoproteins: Evidencethat APOC-III plays a major role in the formation of lipid precursors withinthe microsomal lumen. Journal of Biological Chemistry. 286:27769-27780.
- 2011 McFie P.J., Banman, S.L., Kary, S. and Stone, S.J. Murine Diacylglycerol Acyltransferase-2 (DGAT2) Can Catalyze Triacylglycerol Synthesis and Promote Lipid Droplet FormationIndependent Of Its Localization To The Endoplasmic Reticulum. Journal of Biological Chemistry.286:28235-28246.
- 2011 McFie P.J.and Stone, S.J. A Fluorescent Assay to Quantitatively Measure in vitro Acyl CoA:Diacylglycerol Acyltransferaseactivity. Journal of Lipid Research. 52:1760-1764.
- 2011 Harris,C.A, Haas, J.T., Streeper, R.S., Stone, S.J.,Kumari, M., Yang, K. , Han, X., Brownell, N., Gross, R.W., Zechner,R.., Farese, R.V. Jr. DGAT enzymes are required for triacylglycerolsynthesis and lipid droplets in adipocytes. Journal ofLipid Research. 52:657-667.
- 2010 McFie P.J., Stone S.L., Banman S.L., Stone S.J.Topological orientation ofacyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) and identification of aputative active site histidine and the role of the N-terminus in dimer/tetramerformation. Journalof Biological Chemistry. 285:37377-37387. Publishedon September 27, 2010 [doi:10.1074/jbc.M110.163691].
- 2009 Stone S.J., Levin M., Zhou P., Han J., Walther, T. and Farese R.V. Jr. The Endoplasmic Reticulum Enzyme DGAT2 Is Found in Mitochondria-Associated Membranes and has a Mitochondrial Targeting Signal that Promotes Its Association with Mitochondria. Journal of Biological Chemistry. 284:5352-5361.
- 2008 Yen, C.L., Stone, S.J., Koliwad, S.,Harris, C., Farese, R.V. Jr. Thematic Review Series: Glycerolipids. DGAT Enzymes and TriacylglycerolBiosynthesis. Journal of Lipid Research. 49:2283-2301.