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Open Access Research article

C57Bl/6 N mice on a western diet display reduced intestinal and hepatic cholesterol levels despite a plasma hypercholesterolemia

Charles Desmarchelier1*, Christoph Dahlhoff12, Sylvia Keller3, Manuela Sailer1, Gerhard Jahreis3 and Hannelore Daniel1

Author Affiliations

1 Molecular Nutrition Unit, Technische Universität München, Molecular Nutrition Unit, Gregor-Mendel-Strasse 2, 85350 Freising Weihenstephan, Germany

2 PhD Graduate School 'Epigenetics, Imprinting and Nutrition', ZIEL -Research Center for Nutrition and Food Sciences, Technische Universität München (TUM), 85350 Freising Weihenstephan, Germany

3 Friedrich Schiller University, Institute of Nutrition, 07743 Jena, Germany

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BMC Genomics 2012, 13:84  doi:10.1186/1471-2164-13-84

Published: 6 March 2012

Abstract

Background

Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be determined.

Methods

We therefore measured cholesterol and phospholipid concentration in intestine and liver and quantified fecal neutral sterol and bile acid excretion in C57Bl/6 N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat Western diet containing 0.03% (w/w) cholesterol. To identify the underlying mechanisms of dietary adaptations in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively.

Results

Mice on Western diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry.

Conclusions

Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load.