Boiled coffee fails to raise serum cholesterol in hamsters and rats

Beynen, A.C.; Wouw, M.P.M.E. Weusten-van der; Roos, Baukje de; Katan, Martijn B.

doi:10.1079/bjn19960081

Cited by 22 publications

(17 citation statements)

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“…5 The availability of an animal model to study this hypothesis in vivo would be of great value, since it may help us to validate our in vitro experiments and eventually to discover the metabolic control points of cafestol. However, in previous studies, various animal models like hamsters 6 -8 ; rats 6,9 ; gerbils 8 ; and Cebus, Rhesus, and African green monkeys 10 did not respond to cafestol and kahweol as humans do, regardless of the dosage, the mode of administration, or the duration of treatment.…”

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confidence: 99%

Cafestol Increases Serum Cholesterol Levels in Apolipoprotein E*3-Leiden Transgenic Mice by Suppression of Bile Acid Synthesis

Post¹,

Roos²,

Vermeulen³

et al. 2000

ATVB

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Abstract-Cafestol, a diterpene present in unfiltered coffee, potently increases serum cholesterol levels in humans. So far, no suitable animal model has been found to study the biochemical background of this effect. We determined the effect of cafestol on serum cholesterol and triglycerides in different mouse strains and subsequently studied its mechanism of action in apolipoprotein (apo) E*3-Leiden transgenic mice. ApoE*3-Leiden, heterozygous low density lipoproteinreceptor (LDLRϩ/Ϫ) knockout, or wild-type (WT) C57BL/6 mice were fed a high-(0.05% wt/wt) or a low-(0.01% wt/wt) cafestol diet or a placebo diet for 8 weeks. Standardized to energy intake, these amounts are equal to 40, 8, or 0 cups of unfiltered coffee per 10 MJ per day in humans. In apoE*3-Leiden mice, serum cholesterol was statistically significantly increased by 33% on the low-and by 61% on the high-cafestol diet. In LDLRϩ/Ϫ and WT mice, the increases were 20% and 24%, respectively, on the low-cafestol diet and 55% and 46%, respectively, on the high-cafestol diet. These increases were mainly due to a rise in very low density lipoprotein (VLDL) and intermediate density lipoprotein cholesterol in all 3 mouse strains. To investigate the mechanism of this effect, apoE*3-Leiden mice were fed a high-cafestol or a placebo diet for 3 weeks. Cafestol suppressed enzyme activity and mRNA levels of cholesterol 7␣-hydroxylase by 57% and 58%, respectively. mRNA levels of enzymes involved in the alternate pathway of bile acid synthesis, ie, sterol 27-hydroxylase and oxysterol 7␣-hydroxylase, were reduced by 32% and 48%, respectively. The total fecal bile acid output was decreased by 41%. Cafestol did not affect hepatic free and esterified cholesterol, but it decreased LDLR mRNA levels by 37%. The VLDL apoB and triglyceride production rates, as measured after Triton injection, were 2-fold decreased by cafestol, indicating that the number of particles secreted had declined and that there was no change in the amount of triglycerides present in the VLDL particle during cafestol treatment. However, the VLDL particles contained a 4-times higher amount of cholesteryl esters, resulting in a net 2-fold increased secretion of cholesteryl esters. The decrease in triglyceride production was the result of a reduction in hepatic triglyceride content by 52%. In conclusion, cafestol increases serum cholesterol levels in apoE*3-Leiden mice by suppression of the major regulatory enzymes in the bile acid synthesis pathways, leading to decreased LDLR mRNA levels and increased secretion of hepatic cholesterol esters. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans. Key Words: bile acid synthesis Ⅲ cholesterol 7␣-hydroxylase Ⅲ sterol 27-hydroxylase Ⅲ apolipoprotein E*3-Leiden mice Ⅲ cafestol U nfiltered coffee markedly increases serum cholesterol levels in humans. The compounds responsible for this effect are cafestol and kahweol, 2 diterpenes that are present in coffee beans. 1 From our experimen...

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confidence: 99%

Cafestol Increases Serum Cholesterol Levels in Apolipoprotein E*3-Leiden Transgenic Mice by Suppression of Bile Acid Synthesis

Post¹,

Roos²,

Vermeulen³

et al. 2000

ATVB

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“…Boiled coffee (Al-Kanhal et al 1990) and coffee oil (AHM Terpstra, MB Katan, MPME Weusten-van der Wouw, B de Roos and AC Beynen, unpublished results) significantly increased serum cholesterol on both a low-and high-cholesterol diet. However, in two other studies using Wistar rats, serum lipids were not affected by unfiltered coffee (Hostmark et al 1988;Beynen et al 1996), although one of these studies used a background diet which was relatively high in cholesterol (Beynen et al 1996).…”

Section: Coffee Diterpenes Fail To Show Consistent Results In Other Amentioning

confidence: 99%

“…For details of diets and procedures, see p. 552. Change in serum cholesterol (mmol/l) Beynen et al (1996) Fig . 3.…”

Section: Coffee Diterpenes Fail To Show Consistent Results In Other Amentioning

confidence: 99%

“…Plasma levels of alanine aminotransferase (EC 2.6.1.2) did not differ between the placebooil and the coffee-oil periods (Table 1), which indicates that liver cell integrity was not disturbed. In two previous animal studies also, coffee diterpenes did not affect plasma alanine aminotransferase (Terpstra et al 1995;Beynen et al 1996).…”

Section: Effect Of Coffee Diterpenes In African Green Monkeys and Hummentioning

confidence: 99%

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Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

et al. 1999

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fax +31 317 485369Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDLcholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the mechanism of action of cafestol and kahweol. Cafestol and kahweol increased serum lipids in African green monkeys (Cercopithecus aethiops), cebus (Cebus apella) and rhesus (Macaca mulatta) monkeys, hamsters, rats and gerbils differently from the increase in human subjects. In African green monkeys, the rise in total cholesterol was less pronounced than that in human subjects. In addition, the increase in total cholesterol was predominantly due to a rise in HDL-cholesterol rather than LDL-cholesterol. Thus, the rise in plasma lipids might illustrate the mechanism in these monkeys rather than the mechanism in human subjects. In other animal species, cafestol and kahweol did not raise cholesterol consistently. The variability in effects on serum lipids could not be explained by the mode of administration or dose of diterpenes, nor by the amount of cholesterol in the diet. In conclusion, we did not find an animal model in which cafestol and kahweol elevate plasma lipoproteins to the same extent as in human subjects. For the time being, therefore, studies on the mechanism of action should be done preferably in human subjects.

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“…21,22,42 One of the problems in studying the effects of cafestol in a suitable animal model is the fact that various strains of wild-type mice, rats, gerbils, hamsters, rhesus and cebus monkeys do not show the same alterations in triglyceride levels as those seen in humans following cafestol ingestion. [128][129][130] ApoE3Leiden transgenic mice are an established model used in studies relating to hyperlipidemia and atherosclerosis. 131,132 A mutated form of the human APOE3 gene has been introduced resulting in an attenuated clearance of apoB-containing lipoproteins, because of the concomitant expression of ApoE3Leiden and ApoC1 in this strain.…”

Section: Coffee and The Diterpene Cafestolmentioning

confidence: 99%

Dietary modification of metabolic pathways via nuclear hormone receptors

Caiozzi

Wong

Ricketts

2012

Cell Biochemistry & Function

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Nuclear hormone receptors (NHRs), as ligand-dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail.

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Boiled coffee fails to raise serum cholesterol in hamsters and rats

Cited by 22 publications

References 19 publications

Cafestol Increases Serum Cholesterol Levels in Apolipoprotein E*3-Leiden Transgenic Mice by Suppression of Bile Acid Synthesis

Cafestol Increases Serum Cholesterol Levels in Apolipoprotein E*3-Leiden Transgenic Mice by Suppression of Bile Acid Synthesis

Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

Dietary modification of metabolic pathways via nuclear hormone receptors

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