Impact of fasting on the AMPK and PGC-1α axis in rodent and human skeletal muscle: A systematic review

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 •Fasting is believed to improve metabolic health by increasing muscle mitochondria.•This belief is based on evidence that fasting activates AMPK and PGC-1a in mice.•Our results do not support activation of AMPK/PGC-1a by fasting in human muscle.•We also observed inconsistent effects of fasting on AMPK/PGC1a in rodent muscle.•Human data is not consistent with benefits of fasting on muscle mitochondria.