Hyodeoxycholic acid efficiently suppresses atherosclerosis formation and plasma cholesterol levels in mice.
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.
Sehayek
E
E
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021, USA.
Ono
J G
JG
Duncan
E M
EM
Batta
A K
AK
Salen
G
G
Shefer
S
S
Neguyen
L B
LB
Yang
K
K
Lipkin
M
M
Breslow
J L
JL
D000042:Absorption; D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control*; D001646:Bile / Q000378:metabolism; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000502:physiology
D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D011973:Receptors, LDL; D003840:Deoxycholic Acid; C010471:hyodeoxycholic acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases