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Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice

Buhman, Kimberly K., Accad, Michel, Novak, Sabine, Choi, Rebekah S., Wong, Jinny S., Hamilton, Robert L., Turley, Stephen, Farese, Robert V.·2000·Nature Medicine
DOI 10.1038/82153
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Abstract

The importance of cholesterol ester synthesis by acyl CoA:cholesterol acyltransferase (ACAT) enzymes in intestinal and hepatic cholesterol metabolism has been unclear. We now demonstrate that ACAT2 is the major ACAT in mouse small intestine and liver, and suggest that ACAT2 deficiency has profound effects on cholesterol metabolism in mice fed a cholesterol-rich diet, including complete resistance to diet-induced hypercholesterolemia and cholesterol gallstone formation. The underlying mechanism involves the lack of cholesterol ester synthesis in the intestine and a resultant reduced capacity to absorb cholesterol. Our results indicate that ACAT2 has an important role in the response to dietary cholesterol, and suggest that ACAT2 inhibition may be a useful strategy for treating hypercholesterolemia or cholesterol gallstones.

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  • Treatment with ezetimibe protects mice from diet-induced hypercholesterolemia and atherosclerosis.

    “Treatment with EZ protects mice from diet-induced hypercholesterolemia and atherosclerosis (1, 3, 12, 13).”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [3]

  • Free cholesterol deposited into the inner leaflet of the apical plasma membrane by NPC1L1 must subsequently move to the endoplasmic reticulum to be esterified by ACAT2.

    “Free cholesterol deposited into the inner leaflet of the apical PM by NPC1L1 must subsequently move to the ER to be esterified by ACAT2 (3–5).”

    From Aster-dependent nonvesicular transport facilitates dietary cholesterol uptake (2023) · cites this paper as [3]

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Metadata

Authors
Buhman, K. K., Accad, M., Novak, S., Choi, R. S., Wong, J. S., Hamilton, R. L., Turley, S., & Farese, R. V.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2000-12
Volume
6
Issue
12
Pages
1341-1347
ISSN
  • 1078-8956
  • 1546-170X
DOI
10.1038/82153
Cited by
312
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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