%0 Systematic Review %T Impact of fasting on the AMPK and PGC-1α axis in rodent and human skeletal muscle: A systematic review. %A Storoschuk KL %A Lesiuk D %A Nuttall J %A LeBouedec M %A Khansari A %A Islam H %A Gurd BJ %J Metabolism %V 152 %N 0 %D 2024 Mar 27 %M 38154612 %F 13.934 %R 10.1016/j.metabol.2023.155768 %X Based primarily on evidence from rodent models fasting is currently believed to improve metabolic health via activation of the AMPK-PGC-1α axis in skeletal muscle. However, it is unclear whether the skeletal muscle AMPK-PGC-1α axis is activated by fasting in humans. The current systematic review examined the fasting response in skeletal muscle from 34 selected studies (7 human, 21 mouse, and 6 rat). From these studies, we gathered 38 unique data points related to AMPK and 47 related to PGC-1α. In human studies, fasting mediated activation of the AMPK-PGC-1α axis is largely absent. Although evidence does support fasting-induced activation of the AMPK-PGC-1α axis in rodent skeletal muscle, the evidence is less robust than anticipated. Our findings question the ability of fasting to activate the AMPK-PGC-1α axis in human skeletal muscle and suggest that the metabolic benefits of fasting in humans are associated with caloric restriction rather than the induction of mitochondrial biogenesis. Registration: https://doi.org/10.17605/OSF.IO/KWNQY.