RT Journal Article
SR Electronic
T1 Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.16.460597
DO 10.1101/2021.09.16.460597
A1 Priya Balasubramanian
A1 Anne E. Schaar
A1 Grace E. Gustafson
A1 Alex B. Smith
A1 Porsha R. Howell
A1 Angela Greenman
A1 Scott Baum
A1 Ricki J. Colman
A1 Dudley W. Lamming
A1 Gary Diffee
A1 Rozalyn M. Anderson
YR 2021
UL http://biorxiv.org/content/early/2021/09/17/2021.09.16.460597.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.