Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

The loss of skeletal muscle function with age, known as sarcopenia,
significantly reduces independence and quality of life and can have
significant metabolic consequences. Although exercise is effective in
treating sarcopenia it is not always a viable option clinically, and
currently there are no pharmacological therapeutic interventions for
sarcopenia. Here we show that chronic treatment with pan-adiponectin
receptor agonist AdipoRon improved muscle function in male mice by a
mechanism linked to skeletal muscle metabolism and tissue remodeling. In
aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle
functional measures in vivo and ex vivo. Improvements were linked to
changes in fiber type, including an enrichment of oxidative fibers, and an
increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon
treatment improved contractile force and activated the energy sensing
kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome
proliferator activated receptor gamma coactivator 1 alpha). In cultured
cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated
with increased mitochondrial membrane potential, reorganization of
mitochondrial architecture, increased respiration, and increased ATP
production. Furthermore, the ability of AdipoRon to stimulate AMPK and
PGC1a was conserved in nonhuman primate cultured cells. These data show
that AdipoRon is an effective agent for the prevention of sarcopenia in
mice and indicate that its effects translate to primates, suggesting it
may also be a suitable therapeutic for sarcopenia in clinical application.