The effect of colesevelam treatment on bile acid and lipid metabolism and glycemic control in healthy men.
Physiol Res
; 65(6): 995-1003, 2016 12 13.
Article
en En
| MEDLINE
| ID: mdl-27539104
ABSTRACT
The treatment of hypercholesterolemia with bile acid (BA) sequestrants results in upregulation of BA synthesis through the classical pathway initiated by cholesterol 7alpha-hydroxylase (CYP7A1). To characterize the detailed dynamics of serum lipid and BA concentrations and the BA synthesis rate in response to treatment with BA sequestrants and to determine whether the -203A/C promoter polymorphism of the CYP7A1 encoding gene (CYP7A1) affects such a response, this pilot study was carried out in healthy men (8 homozygous for the -203A allele and 8 homozygous for the -203C allele of CYP7A1). The subjects were treated for 28 days with colesevelam and blood was drawn for analysis before and on days 1, 3, 7, 14 and 28 of treatment. The response of lipids, BA, fibroblast growth factor-19 (FGF19) and 7alpha-hydroxy-4-cholesten-3-one (C4) to colesevelam did not differ between carriers of -203A and -203C alleles; their data were then aggregated for further analysis. Colesevelam treatment caused immediate suppression of FGF19 concentration and a fivefold increase in CYP7A1 activity, as assessed from C4 concentration, followed by a 17 % decrease in LDL-cholesterol. Although total plasma BA concentrations were not affected, the ratio of cholic acid/total BA rose from 0.25+/-0.10 to 0.44+/-0.16 during treatment at the expense of decreases in chenodeoxycholic and deoxycholic acid.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glucemia
/
Ácidos y Sales Biliares
/
Colagogos y Coleréticos
/
Metabolismo de los Lípidos
/
Clorhidrato de Colesevelam
Límite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Physiol Res
Asunto de la revista:
FISIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
República Checa