Data from: Ampk alpha2 T172 activation dictates exercise performance and energy transduction in skeletal muscle

AMPK (5′-AMP-activated protein kinase) is an energetic sensor for
metabolic regulation and integration. Here, we employed CRISPR/Cas9 to
generate non-activatable Ampkα knock-in (KI) mice with a mutation of the
threonine 172 phosphorylation site to alanine, circumventing the
limitations of previous genetic interventions that disrupt the protein
stoichiometry. KI mice of Ampkα2, but not Ampkα1, demonstrated phenotypic
changes with increased fat-to-lean mass, impaired endurance exercise
capacity, and diminished mitochondrial maximal respiration and conductance
in skeletal muscle. Integrated temporal multi-omic analysis (proteomics/
phosphoproteomics/ metabolomics) in skeletal muscle at rest and during
exercise establishes a pleiotropic yet imperative role of Ampkα2 T172
activation for glycolytic and oxidative metabolism, mitochondrial
respiration, and contractile function. Importantly, there is a significant
overlap of skeletal muscle proteomic changes in Ampkα2 T172A KI mice with
those of type 2 diabetic patients. Our findings suggest that Ampkα2 T172
activation is critical for exercise performance and energy transduction in
skeletal muscle and may serve as a therapeutic target for type 2 diabetes.