Abstract

Acyl coenzyme A: cholesterol acyl transferase (ACAT) is an intracellular enzyme that catalyses the formation of cholesteryl esters (CE). It has been postulated that this enzyme is responsible for the synthesis of CE in macrophages (in the artery wall), for cholesterol absorption, hepatic VLDL production and adrenal steroidogenesis. In order to determine the role of ACAT in these processes, the PI has developed ACAT knockout mice. These mice will be used to determine ACATs role in these processes. These same mice will be studied alone or after breeding with other knockout mice (apoE or LDL Receptor) and will be used to determine whether ACAT has an important role in atherosclerosis. The PI will also characterize cDNAs that appear to encode two new novel ACAT genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057170-03
Application #
2872949
Study Section
Metabolism Study Section (MET)
Project Start
1997-02-01
Project End
2002-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
J. David Gladstone Institutes
Department
Type
DUNS #
047120084
City
San Francisco
State
CA
Country
United States
Zip Code
94158

  Publications

Zhang, Jun; Kelley, Kathryn L; Marshall, Stephanie M et al. (2012) Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient to prevent diet-induced cholesterol accumulation in the liver and blood. J Lipid Res 53:1144-52
Repa, Joyce J; Buhman, Kimberly K; Farese Jr, Robert V et al. (2004) ACAT2 deficiency limits cholesterol absorption in the cholesterol-fed mouse: impact on hepatic cholesterol homeostasis. Hepatology 40:1088-97
Willner, Emily L; Tow, Bryan; Buhman, Kimberly K et al. (2003) Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc Natl Acad Sci U S A 100:1262-7
Fazio, S; Major, A S; Swift, L L et al. (2001) Increased atherosclerosis in LDL receptor-null mice lacking ACAT1 in macrophages. J Clin Invest 107:163-71
Buhman, K F; Accad, M; Farese, R V (2000) Mammalian acyl-CoA:cholesterol acyltransferases. Biochim Biophys Acta 1529:142-54
Chen, H C; Farese Jr, R V (2000) DGAT and triglyceride synthesis: a new target for obesity treatment? Trends Cardiovasc Med 10:188-92
Farese Jr, R V; Cases, S; Smith, S J (2000) Triglyceride synthesis: insights from the cloning of diacylglycerol acyltransferase. Curr Opin Lipidol 11:229-34
Buhman, K K; Accad, M; Novak, S et al. (2000) Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat Med 6:1341-7
Accad, M; Smith, S J; Newland, D L et al. (2000) Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. J Clin Invest 105:711-9
Cases, S; Novak, S; Zheng, Y W et al. (1998) ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression, and characterization. J Biol Chem 273:26755-64

Showing the most recent 10 out of 11 publications