title: Hyodeoxycholic acid improves HDL function and inhibits atherosclerotic lesion formation in LDLR-knockout mice.
abstract: We examined the effects of a natural secondary bile acid, hyodeoxycholic acid (HDCA), on lipid metabolism and atherosclerosis in LDL receptor-null (LDLRKO) mice. Female LDLRKO mice were maintained on a Western diet for 8 wk and then divided into 2 groups that received chow, or chow + 1.25% HDCA, diets for 15 wk. We observed that mice fed the HDCA diet were leaner and exhibited a 37% (P<0.05) decrease in fasting plasma glucose level. HDCA supplementation significantly decreased atherosclerotic lesion size at the aortic root region, the entire aorta, and the innominate artery by 44% (P<0.0001), 48% (P<0.01), and 94% (P<0.01), respectively, as compared with the chow group. Plasma VLDL/IDL/LDL cholesterol levels were significantly decreased, by 61% (P<0.05), in the HDCA group as compared with the chow diet group. HDCA supplementation decreased intestinal cholesterol absorption by 76% (P<0.0001) as compared with the chow group. Furthermore, HDL isolated from the HDCA group exhibited significantly increased ability to mediate cholesterol efflux ex vivo as compared with HDL of the chow diet group. In addition, HDCA significantly increased the expression of genes involved in cholesterol efflux, such as Abca1, Abcg1, and Apoe, in a macrophage cell line. Thus, HDCA is a candidate for antiatherosclerotic drug therapy.
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., A2-237 CHS, Los Angeles, CA 90095-1679, USA. dshih@mednet.ucla.edu
authors.forename: Diana M
authors.initials: DM
authors.lastname: Shih
authors.forename: Zory
authors.initials: Z
authors.lastname: Shaposhnik
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Meng
authors.forename: Melenie
authors.initials: M
authors.lastname: Rosales
authors.forename: Xuping
authors.initials: X
authors.lastname: Wang
authors.forename: Judy
authors.initials: J
authors.lastname: Wu
authors.forename: Boris
authors.initials: B
authors.lastname: Ratiner
authors.forename: Filiberto
authors.initials: F
authors.lastname: Zadini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zadini
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003840:Deoxycholic Acid / Q000627:therapeutic use*; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D003840:Deoxycholic Acid; C010471:hyodeoxycholic acid
keywords: bile acid; high-density lipoprotein; intestinal cholesterol absorption; low-density lipoprotein; reverse cholesterol transport