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Small molecule adiponectin receptor agonist GTDF protects against skeletal muscle atrophy
- Source :
- Molecular and Cellular Endocrinology. 439:273-285
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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.
- Subjects :
- Lipopolysaccharides
0301 basic medicine
medicine.medical_specialty
Flavonols
Ubiquitin-Protein Ligases
Muscle Proteins
Peroxisome proliferator-activated receptor
Muscle Development
Protective Agents
Biochemistry
Dexamethasone
Cell Line
Myoblasts
Rats, Sprague-Dawley
Small Molecule Libraries
Tripartite Motif Proteins
Mice
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Endocrinology
Atrophy
Glucosides
Internal medicine
medicine
Animals
Myocyte
Muscle, Skeletal
Molecular Biology
Adiponectin receptor 1
chemistry.chemical_classification
Adiponectin
Tumor Necrosis Factor-alpha
Chemistry
Adenylate Kinase
AMPK
Cell Differentiation
medicine.disease
Muscle atrophy
Muscular Atrophy
030104 developmental biology
030220 oncology & carcinogenesis
Calcium
Female
Receptors, Adiponectin
medicine.symptom
C2C12
Subjects
Details
- ISSN :
- 03037207
- Volume :
- 439
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Endocrinology
- Accession number :
- edsair.doi.dedup.....6ffa0a2e068be66776c2728f978c7d29