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

<p>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 <i>Nr1d1, Per2, Cry2</i> and <i>Bmal1</i> 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 <i>in vitro</i>, where administration of PON1 or pomegranate juice modulated circadian period length.</p>