Muscle‐specific AMPK β1β2‐null mice display a myopathy due to loss of capillary density in nonpostural muscles

ABSTRACT AMP‐activated protein kinase (AMPK) is a master regulator of metabolism. While Muscle‐specific AMPK β1β2 double‐knockout (β1β2M‐KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary β1β2M‐KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial‐ and fiber‐type‐specific etiology to the myopathy was ruled out. However, β1β2M‐KO TA muscles displayed significant (P