The Preventive Effects of Pterostilbene on the Exercise Intolerance and Circadian Misalignment of Mice Subjected to Sleep Restriction.

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 kg d ) 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.