Paraoxonase 1 (PON1) and pomegranate influence circadian gene expression and period length

ABSTRACT

The circadian timing system regulates key aspects of mammalian physiology. Here, we analyzed the effect of the endogenous antioxidant paraoxonase 1 (PON1), a high-density lipoprotein-associated lipolactonase that hydrolyses lipid peroxides and attenuates atherogenesis, on circadian gene expression in C57BL/6J and PON1KO mice fed a normal chow diet or a high-fat diet (HFD). Expression levels of core-clock transcripts Nr1d1, Per2, Cry2 and Bmal1 were altered in skeletal muscle in PON1-deficient mice in response to HFD. These findings were supported by circadian bioluminescence reporter assessments in mouse C2C12 and human primary myotubes, synchronized in vitro, where administration of PON1 or pomegranate juice modulated circadian period length.

KEYWORDS:

• Circadian bioluminescence recording
• circadian clock
• pomegranate
• PON1
• skeletal muscle

Acknowledgments

We are grateful to Jacques Philippe (Geneva University Hospital) for constructive comments on this work and to our colleagues Laurent Perrin and Camille Saini (Department of Clinical Medicine, University of Geneva) for help with the experiments.

Declaration of interest

The authors have no conflict of interest to declare. This work was supported by grants from the Swiss National Science Foundation (grant no. 31003A_146475/1 to C.D.), the Sinergia Swiss National Science Foundation (grant no. CRSII3-154405 to C.D.) and by the Technion Rappaport Faculty of Medicine and Institute research funds (to M.A.).

Supplemental Material

Supplemental data for this article can be accessed at www.tandfonline.com/icbi.