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An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training

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Abstract

Purpose

The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training.

Methods

Sprague–Dawley rats (n = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week.

Results

The AD resulted in a large (P < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction (P < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding.

Conclusions

It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.

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Acknowledgments

This work was supported by grants from the Canadian Institutes of Health Research (CIHR; T 0602 145.02) and the Natural Sciences and Engineering Research Council of Canada (NSERC; 7594).

Conflict of interest

All authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Kinesiology, Université de Montréal, C.P. 6128, Succ. centre-ville, Montreal, QC, H3C 3J7, Canada

    Isabelle Côté, Emilienne Tudor Ngo Sock & Jean-Marc Lavoie

  2. Department of Nutrition, Centre de recherche du CHU Ste-Justine, Montreal, QC, Canada

    Émile Lévy

Authors
  1. Isabelle Côté
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  2. Emilienne Tudor Ngo Sock
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  3. Émile Lévy
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  4. Jean-Marc Lavoie
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Correspondence to Jean-Marc Lavoie.

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Côté, I., Ngo Sock, E.T., Lévy, É. et al. An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training. Eur J Nutr 52, 1523–1532 (2013). https://doi.org/10.1007/s00394-012-0459-5

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  • DOI: https://doi.org/10.1007/s00394-012-0459-5

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