The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane x receptors

M.L. Ricketts, M.V. Boekschoten, A.J. Kreeft, G.J. Hooiveld, C.J. Moen, M. Müller, R.R. Frants, S. Kasanmoentalib, S.M. Post, H.M.G. Princen, J.G. Porter, M.B. Katan, M.H. Hofker, D.D Moore

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian boiled, Turkish, and cafetière coffee, is the most potent cholesterol-elevating compound known in the human diet. Several genes involved in cholesterol homeostasis have previously been shown to be targets of cafestol, including cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis. We have examined the mechanism by which cafestol elevates serum lipid levels. Changes in several lipid parameters were observed in cafestol-treated APOE3Leiden mice, including a significant increase in serum triglyceride levels. Microarray analysis of these mice identified alterations in hepatic expression of genes involved in lipid metabolism and detoxification, many of which are regulated by the nuclear hormone receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR). Further studies demonstrate that cafestol is an agonist ligand for FXR and PXR, and that cafestol down-regulates expression of the bile acid homeostatic genes CYP7A1, sterol 12α-hydroxylase, and Na
Original languageEnglish
Pages (from-to)1603-1616
JournalMolecular Endocrinology
Volume21
Issue number7
DOIs
Publication statusPublished - 2007

Fingerprint

Dive into the research topics of 'The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane x receptors'. Together they form a unique fingerprint.

Cite this