title: Dietary hyodeoxycholic acid exerts hypolipidemic effects by reducing farnesoid X receptor antagonist bile acids in mouse enterohepatic tissues.
abstract: Mice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid-supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1. Hyodeoxycholic acid administration markedly changes the ratio of FXR-antagonist/FXR-agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.
authors.affiliation: Department of Nutritional Biochemistry, Institute of Natural Medicines, University of Toyama, Toyama, 930-0194, Japan, shirowat@inm.u-toyama.ac.jp.
authors.forename: Shiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Fujita
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000008:administration & dosage; D003840:Deoxycholic Acid / Q000008:administration & dosage*; D019587:Dietary Supplements; D004764:Enterohepatic Circulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D054890:Fatty Acid Synthase, Type I / Q000235:genetics; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000103:Acetyl-CoA Carboxylase; D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D003840:Deoxycholic Acid; D054890:Fatty Acid Synthase, Type I; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013230:Stearoyl-CoA Desaturase; D051780:Sterol Regulatory Element Binding Protein 1; D000099150:Receptor, Farnesoid X-Activated; C497388:Srebf1 protein, mouse; C010471:hyodeoxycholic acid; C490333:Scd1 protein, mouse