Kopp, R., Billecke, N., Legradi, J., den Broeder, M., Parekh, S.H., Legler, J. (2016) Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?. International journal of obesity (2005). 40(5):824-32.
Background Recent studies have led to an expansion of potential factors capable of stimulating obesity. Increasing evidence indicates that also environmental factors, including disturbance of circadian rhythms, 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 quantified by qRT-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
RESULTSZebrafish larvae exposed to continuous light (LL) had a 7 fold higher prevalence of adipocytes compared to control fish under a 14 h light and 10 h dark cycle. It was also significantly higher than in HCF larvae with control light/dark cycle, which showed a 5.5 fold increase compared to control animals. Though 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 Reverbα and Pparγ co-localize in adipocytes, which together with the gene expression analysis, suggests interplay between Reverbα and Ppar isoforms.
Conclusion The amount of light but not shifted light/dark cycles affected adipogenesis and lipid composition, possibly due to increased period2 expression that 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.