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J. Biol. Chem., Vol. 277, Issue 28, 25474-25479, July 12, 2002
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From the Dietary triacylglycerols are a major source of
energy for animals. The absorption of dietary triacylglycerols involves
their hydrolysis to free fatty acids and monoacylglycerols in the
intestinal lumen, the uptake of these products into enterocytes, the
resynthesis of triacylgylcerols, and the incorporation of newly
synthesized triacylglycerols into nascent chylomicrons for secretion.
In enterocytes, the final step in triacylglycerol synthesis is believed
to be catalyzed primarily through the actions of
acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. In this study,
we analyzed intestinal triacylglycerol absorption and chylomicron
synthesis and secretion in DGAT1-deficient
(Dgat1
DGAT1 Is Not Essential for Intestinal Triacylglycerol Absorption
or Chylomicron Synthesis*
§,§,§,
,,,§¶¶
Gladstone Institute of Cardiovascular
Disease, San Francisco, California 94141-9100, the
§ Cardiovascular Research Institute, Departments of
¶¶ Medicine and Anatomy, University of California,
San Francisco, California 94143, the ¶ Department of Pharmacology,
University of Texas Southwestern Medical Center, Dallas, Texas
75390-9050, the ** Nuclear Medicine Program, Oak Ridge
National Laboratory, Oak Ridge, Tennessee 37831, The
Western Human Nutrition Research Center, United States Department of
Agriculture, Davis, California 95616, and the
§§ Department of Physiology and Biophysics,
State University of New York, Stony Brook, New York 11793-8661
/) mice. Surprisingly, DGAT1 was not
essential for quantitative dietary triacylglycerol absorption, even in
mice fed a high fat diet, or for the synthesis of chylomicrons.
However, Dgat1/ mice had reduced
postabsorptive chylomicronemia (1 h after a high fat challenge) and
accumulated neutral-lipid droplets in the cytoplasm of enterocytes when
chronically fed a high fat diet. These results suggest a reduced rate
of triacylglycerol absorption in Dgat1/
mice. Analysis of intestine from Dgat1/
mice revealed activity for two other enzymes, DGAT2 and diacylglycerol transacylase, that catalyze triacylglycerol synthesis and apparently help to compensate for the absence of DGAT1. Our findings indicate that
multiple mechanisms for triacylglycerol synthesis in the intestine
facilitate triacylglycerol absorption.
*
This work was supported by National Institutes of Health
(NIH) Grant DK56084 (to R. V. F.), a NIH postdoctoral
fellowship training grant (to K. K. B. and S. J. Smith),
a Canadian Institute of Health Research postdoctoral fellowship (to
S. J. Stone), the Howard Hughes Medical Institutes (to J. J. R.), and the J. David Gladstone Institutes. Research at Oak
Ridge National Laboratory was supported by DOE Contract
DE-AC05-00OR22725 with UT-Battelle, LLC.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Gladstone
Inst. of Cardiovascular Disease, San Francisco, CA 94141-9100. Tel.: 415-826-7500; Fax: 415-285-5632; E-mail:
bfarese@gladstone.ucsf.edu.
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