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Metabolism as a Target for Age‐Related Muscle Mass and Functional Loss
Author(s) -
Schaar Anne,
Balasubramanian Priya,
Diffee Gary,
Anderson Rozalyn
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.01832
Subject(s) - skeletal muscle , sarcopenia , endocrinology , medicine , adiponectin receptor 1 , adiponectin , myostatin , gastrocnemius muscle , soleus muscle , glycolysis , pdk4 , metabolism , biology , chemistry , insulin , gene expression , insulin resistance , biochemistry , gene
The progressive age‐related loss of skeletal muscle mass and function, known as sarcopenia, increases the risk for impaired mobility, falls, fractures, and mortality. Currently, there are no pharmacological interventions to prevent or treat sarcopenia. Here we show that stimulation of adiponectin signaling in skeletal muscle by AdipoRon, a pan‐adiponectin receptor agonist, stimulates pathways linked to exercise and improves muscle function in old mice. Intravenous delivery of AdipoRon (1.2mg/kg bw; 3 times per week, 6 weeks) activated the AMPK‐PGC‐1a axis in skeletal muscle and induced changes in fiber type distribution in young (5 months) and old (24 months) male C57Bl6/J mice. In old mice, AdipoRon treatment improved running endurance and muscle contractile force. To explore mechanisms and enhance translational potential, the response to oral delivery through diet of AdipoRon (10, 25, or 50 mg/kg; daily feeding, 16 weeks) was investigated in young male and female C3B6F1 mice. AdipoRon enhanced insulin sensitivity and decreased body mass in females, however, these changes were not displayed in males. Increased expression of Ppargc1a and ACADM were observed in EDL of male mice in response to AdipoRon treatment and a decrease in expression of PDK4 was observed in both gastrocnemius and soleus indicating a shift toward oxidative metabolism in all muscle types. Conversely, these changes at the gene expression level were not observed in the female mice. Overall, AdipoRon treatment induced changes in the relative proportions of oxidative and glycolytic muscle fibers in EDL, gastrocnemius, and soleus; however, the skeletal muscle remodeling response to AdipoRon was muscle type and sex specific. In both sexes, the greatest response to AdipoRon was detected in EDL, which is the more glycolytic of the three muscle groups investigated. These data uncover differences in the underlying biology of skeletal muscle between males and females that may have implications for sarcopenia treatment. Taken together, our studies show that AdipoRon has potential as a therapeutic for sarcopenia in males and although sex dimorphic in its mechanism of action, is likely to also be effective as a treatment for sarcopenia in females. Support or Funding Information 1I01BX003846‐01A2