1. Small molecule adiponectin receptor agonist GTDF protects against skeletal muscle atrophy.
- Author
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Singh AK, Shree S, Chattopadhyay S, Kumar S, Gurjar A, Kushwaha S, Kumar H, Trivedi AK, Chattopadhyay N, Maurya R, Ramachandran R, and Sanyal S
- Subjects
- Adenylate Kinase metabolism, Adiponectin pharmacology, Animals, Calcium pharmacology, Cell Differentiation drug effects, Cell Line, Dexamethasone, Female, Flavonols pharmacology, Glucosides pharmacology, Lipopolysaccharides, Mice, Muscle Development drug effects, Muscle Proteins metabolism, Muscular Atrophy pathology, Myoblasts drug effects, Myoblasts pathology, Phosphatidylinositol 3-Kinases metabolism, Protective Agents pharmacology, Rats, Sprague-Dawley, Receptors, Adiponectin metabolism, Small Molecule Libraries pharmacology, Tripartite Motif Proteins metabolism, Tumor Necrosis Factor-alpha, Ubiquitin-Protein Ligases metabolism, Flavonols therapeutic use, Glucosides therapeutic use, Muscle, Skeletal pathology, Muscular Atrophy drug therapy, Protective Agents therapeutic use, Receptors, Adiponectin agonists, Small Molecule Libraries therapeutic use
- Abstract
Skeletal muscle atrophy is a debilitating response to several major diseases, muscle disuse and chronic steroid treatment for which currently no therapy is available. Since adiponectin signaling plays key roles in muscle energetics, we assessed if globular adiponectin (gAd) or the small molecule adiponectin mimetic 6-C-β-D-glucopyranosyl-(2S,3S)-(+)-5,7,3',4'-tetrahydroxydihydroflavonol (GTDF) could ameliorate muscle atrophy. Both GTDF and gAd induced C2C12 myoblast differentiation. GTDF and gAd effectively prevented reduction in myotube area and suppressed the expressions of atrophy markers; atrogin-1 and muscle ring finger protein-1 (MuRF1) in models of steroid, cytokine and starvation -induced muscle atrophy. The protective effects of GTDF and gAd were routed through AMPK and AKT activation and thereby stimulation of PPAR gamma coactivator 1α and inhibition of forkhead box O transcription factors. Finally, GTDF and gAd mitigated dexamethasone-induced muscle atrophy in vivo. Together, our results demonstrate that activating adiponectin signaling may be an effective therapeutic strategy against skeletal muscle atrophy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2017
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