Key result
Exercise regulates the Hippo signaling network to mediate skeletal muscle hypertrophy and fiber type switching.
This review highlights the role of the Hippo signaling network in mediating physiological adaptations to exercise in skeletal and cardiac muscle.
No immediate changes to exercise prescriptions; leaves open Hippo-Yap/Taz modulation as targets for future adaptation trials.
The ubiquitous transcriptional coactivators Yap (gene symbol Yap1) and Taz (gene symbol Wwtr1) regulate gene expression mainly by coactivating the Tead transcription factors. Being at the center of the Hippo signaling network, Yap and Taz are regulated by the Hippo kinase cassette and additionally by a plethora of exercise-associated signals and signaling modules. These include mechanotransduction, the AKT-mTORC1 network, the SMAD transcription factors, hypoxia, glucose homeostasis, AMPK, adrenaline/epinephrine and angiotensin II through G protein-coupled receptors, and IL-6. Consequently, exercise should alter Hippo signaling in several organs to mediate at least some aspects of the organ-specific adaptations to exercise. Indeed, Tead1 overexpression in muscle fibers has been shown to promote a fast-to-slow fiber type switch, whereas Yap in muscle fibers and cardiomyocytes promotes skeletal muscle hypertrophy and cardiomyocyte adaptations, respectively. Finally, genome-wide association studies in humans have linked the Hippo pathway members LATS2, TEAD1, YAP1, VGLL2, VGLL3, and VGLL4 to body height, which is a key factor in sports.
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Gabriel et al. (2016) conducted a review in Exercise physiology and Hippo signaling network. Exercise was evaluated. The Hippo signaling network, centered on Yap and Taz, is regulated by exercise-associated signals to mediate organ-specific adaptations such as skeletal muscle hypertrophy and fiber type switching.
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