{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:50:23Z","timestamp":1791352223328,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T00:00:00Z","timestamp":1485907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003514","name":"Kommunfullm\u00e4ktige, Stockholms Stad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The natural farnesoid X receptor (\n FXR<\/jats:styled-content>\n ) agonist chenodeoxycholic acid (\n CDCA<\/jats:styled-content>\n ) suppresses hepatic cholesterol and bile acid synthesis and reduces biliary cholesterol secretion and triglyceride production. Animal studies have shown that bile acids downregulate hepatic\n LDL<\/jats:styled-content>\n receptors (\n LDLR<\/jats:styled-content>\n s); however, information on\n LDL<\/jats:styled-content>\n metabolism in humans is limited.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Kinetics of autologous\n 125<\/jats:sup>\n I\u2010\n LDL<\/jats:styled-content>\n were determined in 12 male subjects at baseline and during treatment with\n CDCA<\/jats:styled-content>\n (15 mg kg\n \u22121<\/jats:sup>\n day\n \u22121<\/jats:sup>\n ). In seven patients with gallstones treated with\n CDCA<\/jats:styled-content>\n for 3 weeks before cholecystectomy, liver biopsies were collected and analysed for enzyme activities and for specific\n LDLR<\/jats:styled-content>\n binding. Serum samples obtained before treatment and at surgery were analysed for markers of lipid metabolism, lipoproteins and the\n LDLR<\/jats:styled-content>\n modulator proprotein convertase subtilisin\/kexin type 9 (\n PCSK<\/jats:styled-content>\n 9).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Chenodeoxycholic acid treatment increased plasma\n LDL<\/jats:styled-content>\n cholesterol by ~10% as a result of reduced clearance of plasma\n LDL<\/jats:styled-content>\n \u2010apolipoprotein (apo)B;\n LDL<\/jats:styled-content>\n production was somewhat reduced. The reduction in\n LDL<\/jats:styled-content>\n clearance occurred within 1 day after initiation of treatment. In\n CDCA<\/jats:styled-content>\n \u2010treated patients with gallstones, hepatic microsomal cholesterol 7\u03b1\u2010hydroxylase and\n HMG<\/jats:styled-content>\n \u2010CoA reductase activities were reduced by 83% and 54%, respectively, and specific\n LDLR<\/jats:styled-content>\n binding was reduced by 20%. During treatment, serum levels of fibroblast growth factor 19 and total and\n LDL<\/jats:styled-content>\n cholesterol increased, whereas levels of 7\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one, lathosterol,\n PCSK<\/jats:styled-content>\n 9, apoA\u2010I, apoC\u2010\n III<\/jats:styled-content>\n , lipoprotein(a), triglycerides and insulin were reduced.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Chenodeoxycholic acid has a broad influence on lipid metabolism, including reducing plasma clearance of\n LDL<\/jats:styled-content>\n . The reduction in circulating\n PCSK<\/jats:styled-content>\n 9 may dampen its effect on hepatic\n LDLR<\/jats:styled-content>\n s and plasma\n LDL<\/jats:styled-content>\n cholesterol. Further studies of the effects of other\n FXR<\/jats:styled-content>\n agonists on cholesterol metabolism in humans seem warranted, considering the renewed interest for such therapy in liver disease and diabetes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/joim.12594","type":"journal-article","created":{"date-parts":[[2017,2,1]],"date-time":"2017-02-01T04:24:56Z","timestamp":1485923096000},"page":"575-585","source":"Crossref","is-referenced-by-count":67,"title":["Treatment with the natural\n FXR<\/scp>\n agonist chenodeoxycholic acid reduces clearance of plasma\n LDL<\/scp>\n whilst decreasing circulating\n PCSK<\/scp>\n 9, lipoprotein(a) and apolipoprotein C\u2010\n III<\/scp>"],"prefix":"10.1111","volume":"281","author":[{"given":"M.","family":"Ghosh Laskar","sequence":"first","affiliation":[{"name":"Metabolism Unit Department of Endocrinology, Metabolism and Diabetes Karolinska Institutet Karolinska University Hospital Huddinge Stockholm Sweden"},{"name":"Molecular Nutrition Unit 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