ArticleJournal of cachexia, sarcopenia and muscle2025
HD6277 Suppresses Muscle Atrophy by Promoting Myogenic Factors and Inhibiting Proteolysis in Aged Mice.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Efficacy and Safety of HD-6277, a Novel G Protein-Coupled Receptor 40 Agonist, in Individuals with Type 2 Diabetes Mellitus: A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 2 Clinical Trial.Diabetes & metabolism journal · 2026Trial
- Ameliorative Effects of Pumpkin Seed Protein Peptides on Dexamethasone-Treated Sarcopenia and Their Effects When Combined with Vitamin D.Foods (Basel, Switzerland) · 2026Article
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10 authors.
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Abstract
backgroundG protein-coupled receptor 40 (GPR40) acts as a modulator of various physiological functions, including glycaemic lowering, anti-inflammation and antioxidative stress, in several tissues. However, the role of GPR40 in skeletal muscles remains unclear.
methodsTo investigate the roles of muscle GPR40, C2C12 myoblasts and myotubes were stimulated with palmitate and HD6277, a GPR40 agonist. Muscle strength and myofiber thickness were measured in obese and aged mice fed HD6277.
resultsIn C2C12 myoblasts, the addition of HD6277 induced phosphorylated Akt levels and expression of the myogenic factors, myogenin (MyoG), myocyte enhancer factor 2C (Mef2c) and myosin heavy chain (MyHC, p < 0.05). These changes resulted in accelerated muscle differentiation from myoblasts to myotubes (MyHC-positive area +56.52%; myotube width +34.08% vs. Veh, p < 0.05). In C2C12 myotubes, a palmitate-mediated decrease in the phosphorylation of forkhead box protein O1A (FOXO1A) and increase in the expression of E3 ubiquitin ligases, atrogin-1 and muscle RING-finger protein 1 (MuRF1) were reversed by HD6277 (p < 0.05). Additionally, HD6277 inhibited palmitate-induced apoptotic events such as the Bcl-2 (Bcl2)-associated X protein (Bax)/Bcl-2 ratio, caspase 3 cleavage and nuclear fragmentation in C2C12 myoblasts and myotubes (p < 0.05). These beneficial HD6277-mediated actions disappeared after the addition of an Akt inhibitor (p < 0.05). Similar to in vitro studies, HD6277 administration in obese and aged mice increased myogenic factors and decreased E3 ubiquitin ligase expression and apoptotic events (p < 0.05). HD6277 increased muscle strength (+9.88% vs. Aged, p < 0.05) and myofiber thickness (+29.01% vs. Aged, p < 0.05) in aging mice but only improved myofiber thickness (+11.84% vs. HFD, p < 0.05) in obese mice.
conclusionHD6277 can increase myogenic factors and reduce E3 ligase-mediated proteolysis to inhibit muscle atrophy in aged mice. Our results suggest that GPR40 agonists may have potential as therapeutic agents for sarcopenia.
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