Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice

Ephraim Sehayek, Jennie G. Ono, Elizabeth M. Duncan, Ashok K. Batta, Gerald Salen, Sarah Shefer, Lien B. Neguyen, Kan Yang, Martin Lipkin, Jan L. Breslow

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

We examined the effect of hyodeoxycholic acid (HDCA) on plasma cholesterol levels and atherosclerosis in mice. In wild-type C57BL/6 mice, feeding increasing amounts of HDCA resulted in i) progressive decrease in dietary cholesterol absorption, ii) increased concentrations of HDCA in the gallbladder bile, iii) decreased liver cholesterol content, iv) increased liver cholesterol synthesis, and v) increased plasma concentrations of HDCA. In C57BL/6 LDL-receptor knockouts (LDLR-KO) the addition of HDCA to chow and a 0.5% cholesterol diet decreased their total plasma cholesterol levels by 21% and 62%, respectively, because of a decrease in VLDL and LDL cholesterol. Turnover studies showed that HDCA has no effect on VLDL removal from plasma. Furthermore, the addition of HDCA to chow- and 0.5% cholesterol-fed LDLR-KO mice decreased the aortic root atherosclerosis lesion area by 50% and 80%, respectively. Finally, we tested the effect of HDCA on intestinal tumor formation. Feeding C57BL/6 ApcMin mice with HDCA did not affect the number of tumors but decreased the tumor volume in these animals. These results suggest that HDCA might have beneficial effects in the treatment of increased plasma cholesterol levels and atherosclerosis.

Original languageEnglish
Pages (from-to)1250-1256
Number of pages7
JournalJournal of Lipid Research
Volume42
Issue number8
StatePublished - 2001

Keywords

  • Bile acids
  • Cholesterol absorption
  • Colon cancer
  • Dietary cholesterol
  • LDL-receptor knockout

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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