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Molecular
Biology of Cellular Lipid Metabolism
Our laboratory investigates the molecular biology of cellular lipid metabolism
with an emphasis on neutral lipid metabolism. Neutral lipids, such as
triglycerides and cholesterol esters, are highly hydrophobic molecules
that are important in many physiologic and pathologic processes, including
energy storage, lipoprotein assembly, lactation, sebaceous gland secretion,
and steroidogenesis. Cholesterol esters accumulate in atherosclerotic
lesions in arteries and triglycerides accumulate in adipose tissue of
obese individuals. Our laboratory has focused on the functional analysis
of enzymes involved in neutral lipid synthesis. These include acyl CoA:diacylglycerol
acyltransferase (DGAT), which catalyzes triglyceride synthesis, and acyl
CoA:cholesterol acyltransferase (ACAT), which catalyzes cholesterol ester
synthesis.
Selected Publications:
Cases S, Smith SJ, Zheng Y-W, Myers HM, Lear SR, Sande E, Novak S, Collins
C, Welch CB, Lusis AJ, Erickson SK, Farese RV Jr (1998) Identification
of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme
in triacylglycerol synthesis. Proc. Natl. Acad. Sci. USA 95:13018Ð13023.
Smith SJ, Cases S, Jensen DR, Chen HC, Sande E, Tow B, Sanan DA, Raber
J, Eckel RH, Farese RV Jr (2000) Obesity resistance and multiple mechanisms
of triglyceride synthesis in mice lacking DGAT. Nat. Genet. 25:87Ð90.
Chen HC, Farese RV Jr (2000) DGAT and triglyceride synthesis: A new target
for obesity treatment? Trends Cardiovasc. Med. 10:188Ð192.
Meiner VL, Cases S, Myers HM, Sande ER, Bellosta S, Schambelan M, Pitas
RE, McGuire J, Herz J, Farese RV Jr (1996) Disruption of the acyl-CoA:cholesterol
acyltransferase gene in mice: Evidence suggesting multiple cholesterol
esterification enzymes in mammals. Proc. Natl. Acad. Sci. USA 93:14041Ð14046.
Cases S, Novak S, Zheng Y-W, Myers HM, Lear SR, Sande E, Welch CB, Lusis
AJ, Spencer TA, Krause BR, Erickson SK, Farese RV Jr (1998) ACAT-2, a
second mammalian acyl-CoA:cholesterol acyltransferase. Its cloning, expression,
and characterization. J. Biol. Chem. 273:26755Ð26764.
Buhman KK, Accad M, Novak S, Choi RS, Wong JS, Hamilton RL, Turley S,
Farese RV Jr (2000) Resistance to diet-induced hypercholesterolemia and
gallstone formation in ACAT2-deficient mice. Nat. Med. 6:1341Ð1347.
Accad M, Smith SJ, Newland DL, Sanan DA, King LE Jr, Linton MF, Fazio
S, Farese RV Jr (2000) Massive xanthomatosis and altered composition of
atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol
acyltransferase 1. J. Clin. Invest. 105:711Ð719.
8. Terasawa Y, Ladha Z, Leonard SW, Morrow JD, Newland D, Sanan D, Packer
L, Traber MG, Farese RV Jr (2000) Increased atherosclerosis in hyperlipidemic
mice deficient in a-tocopherol transfer protein and vitamin E. Proc. Natl.
Acad. Sci. USA 97:13830Ð13834.
Contact Information:
Email: bfarese@gladstone.ucsf.edu
Phone: 415/ 826-7500
Address: Box 1230, SFGH Bldg 40, Room 430
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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