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Animal Models

Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

International Journal of Obesity volume 38, pages 1027–1034 (2014)Cite this article

Subjects

Abstract

Objective:

Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice.

Research design:

To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt−1, mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt−1) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion).

Results:

In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation.

Conclusions:

CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.

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Acknowledgements

JST, FVD, APG and ATV were recipients of a Fundação para a Ciência e a Tecnologia PhD scholarship (SFRH/BD/38467/2007, SFRH/BD/38372/2007, SFRH/BD/44674/2008 and SFRH/BD/44796/2008, respectively). This project was supported by a FCT grant PTCD/SAU-OSM/72443/2006, PEst-C/SAU/LA0001/2011 and EU FP7 project DIABAT (HEALTH-F2—2011-278373) and by the Czech Science Foundation (13-00871S).

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Author notes

  1. J S Teodoro and P Zouhar: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal

    J S Teodoro, A P Gomes, F V Duarte, A T Varela, A P Rolo & C M Palmeira

  2. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal

    J S Teodoro, A P Gomes, F V Duarte, A T Varela & C M Palmeira

  3. Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic

    P Zouhar, P Flachs, K Bardova, P Janovska & J Kopecký

  4. Department of Biology, University of Aveiro, Aveiro, Portugal

    A P Rolo

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  1. J S Teodoro
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Teodoro, J., Zouhar, P., Flachs, P. et al. Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice. Int J Obes 38, 1027–1034 (2014). https://doi.org/10.1038/ijo.2013.230

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