We developed a non-invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non-light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non-image-forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders.

SCOPE:The study investigates the effects of pterostilbene (PTE) on exercise endurance and circadian rhythm in sleep-restricted (SR) mice.

METHODS AND RESULTS:The SR model is established by keeping mice awake during the first 8 h of light period for 5 d and PTE (100 mg kgd) is given once a day. PTE improves endurance in SR mice by significantly prolonging the exhaustive swimming time and ameliorating exercise fatigue biochemical parameters, including creatine kinase and lactate dehydrogenase. It is observed that PTE effectively regained mitochondrial function by improving mitochondrial swelling and maintaining oxidative phosphorylation system-related genes expression, and inhibited the decrease of mitochondrial biogenesis-related genes expression. Furthermore, PTE restores rhythms of AMP-activated protein kinase (AMPK) phosphorylation activity, silent information regulator 1 (SIRT1) deacetylation activity, and SIRT1-mediated peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) deacetylation in SR mice. Finally, the results demonstrate that the AMPK/SIRT1/PGC-1α pathway may be correlated with the relationships between mitochondrial function and circadian rhythms, markedly regulating the expression of skeletal muscle clock genes, circadian locomotor output cycles kaput, and brain and muscle arnt-like 1.

CONCLUSIONS:PTE ameliorates SR-induced exercise intolerance associated with circadian misalignment and mitochondrial dysfunction through AMPK/SIRT1/PGC-1α pathway.