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Animal Models

Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?

International Journal of Obesity volume 40, pages 824–832 (2016)Cite this article

Subjects

Abstract

Background:

Recent studies have led to an expansion of potential factors capable of stimulating obesity. Increasing evidence indicates that environmental factors, including disturbance of circadian rhythms, also contribute to its etiology.

Objectives:

To determine the effects of altered circadian rhythms on adipogenesis and to better understand how circadian and adipogenic regulatory pathways are linked, zebrafish larvae were exposed to various light/dark cycles or hypercaloric feeding (HCF).

Methods:

Clock and adipogenic gene expression was quantitative real time PCR. Adipogenesis was characterized using coherent anti-Stokes Raman scattering microscopy (CARS) and whole-mount lipid composition was analyzed by gas chromatography. The clock protein Rev-erbα and the adipogenesis-regulating protein Pparγ were localized by immunohistochemistry.

Results:

Zebrafish larvae exposed to continuous light (LL) had a sevenfold higher prevalence of adipocytes compared with control fish under a 14 h light and 10 h dark cycle. It was also significantly higher compared with that in HCF larvae with control light/dark cycle, which showed a 5.5-fold increase compared with control animals. Although total fatty acid content was unaffected, adipocyte lipid composition was altered in LL zebrafish. In contrast, shifting the onset and duration of the light periods did not affect adipogenesis or total fatty acid content. Gene expression analysis revealed effects of LL and HCF on circadian cyclicity, with increased expression of the clock gene period2 and altered circadian rev-erbα expression in LL larvae. Immunostaining revealed for the first time that Rev-erbα and Pparγ colocalize in adipocytes, which together with the gene expression analysis suggests interplay between Rev-erbα and Ppar isoforms.

Conclusions:

The amount of light, but not shifted light/dark cycles, affected adipogenesis and lipid composition, possibly due to increased period2 expression, which, in turn, enhances Rev-erbα-regulated gene expression. As the pparβδ promoter includes three Rev-erbα binding sites, we hypothesize that pparβδ may be a direct target that ultimately activates Pparγ.

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Acknowledgements

We thank Jurjen Broeke, Peter Cenijn, Philip Nijssen, Gerda Hopman-Ubbels and the Animal Caretakers of the VU University Amsterdam for their support in carrying out the experiments. We acknowledge the financial support by the European Union (FP7-PEOPLE-IEF, 303197 Obesity and Light and the Marie Curie Foundation No. CIG322284) and the Netherlands Organization for Scientific Research (VIDI/864.09.005).

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Authors and Affiliations

  1. Institute for Environmental Studies (IVM), VU University Amsterdam, Amsterdam, The Netherlands

    R Kopp, J Legradi, M den Broeder & J Legler

  2. Department of Molecular Spectroscopy, Max Planck Institute for Polymer Research, Mainz, Germany

    N Billecke & S H Parekh

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  1. R Kopp
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Correspondence to R Kopp or J Legler.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Kopp, R., Billecke, N., Legradi, J. et al. Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?. Int J Obes 40, 824–832 (2016). https://doi.org/10.1038/ijo.2015.240

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