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

Kimberly K. Buhman, Michel Accad, Sabine Novak, Rebekah S. Choi, Jinny S. Wong, Robert L. Hamilton, Stephen Turley, Robert V. Farese

Research output: Contribution to journalArticle

257 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1341-1347
Number of pages7
JournalNature Medicine
Volume6
Issue number12
DOIs
StatePublished - 2000

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Gallstones
Nutrition
Hypercholesterolemia
Cholesterol
Diet
Sterol O-Acyltransferase
Cholesterol Esters
Metabolism
Dietary Cholesterol
Liver
Small Intestine
Intestines
Enzymes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Buhman, K. K., Accad, M., Novak, S., Choi, R. S., Wong, J. S., Hamilton, R. L., ... Farese, R. V. (2000). Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nature Medicine, 6(12), 1341-1347. https://doi.org/10.1038/82153

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.

In: Nature Medicine, Vol. 6, No. 12, 2000, p. 1341-1347.

Research output: Contribution to journalArticle

Buhman, KK, Accad, M, Novak, S, Choi, RS, Wong, JS, Hamilton, RL, Turley, S & Farese, RV 2000, 'Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice', Nature Medicine, vol. 6, no. 12, pp. 1341-1347. https://doi.org/10.1038/82153
Buhman, Kimberly K. ; Accad, Michel ; Novak, Sabine ; Choi, Rebekah S. ; Wong, Jinny S. ; Hamilton, Robert L. ; Turley, Stephen ; Farese, Robert V. / Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. In: Nature Medicine. 2000 ; Vol. 6, No. 12. pp. 1341-1347.
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