Metformin-induced metabolic reprogramming inhibits the proliferation and differentiation of myoblasts
Pu Rongxi
Bu Fan
Huang Siyuan
Yang Zhong
Abstract：Objective To investigate the effects and mechanisms of metformin-induced metabolic intervention on the proliferation and differentiation of myoblasts.Methods C2C12 myoblasts cultured in growth or differentiation media were treated with 1 mmol/L metformin,with DMSO as the control.Cells in growth media were treated for 48 hours,with samples collected every 12 hours for metabolomic analysis,protein expression,mitochondrial function,and proliferation assays.Cells in differentiation media were induced to differentiate for 72 hours,and myotube formation was assessed via embryonic myosin heavy chain immunofluorescence staining.Results Metformin treatment increased intracellular levels of metabolites such as lactate,pyruvate,and adenosine monophosphate,while reducing adenosine triphosphate and thiamine pyrophosphate.Phosphorylation of AMP-activated protein kinase(AMPK)and related protein expression were significantly upregulated(P<0.05).Mitochondrial biogenesis was enhanced,and membrane potential markedly decreased(P<0.05).The proportion of S-phase cells and EdU-positive cells gradually increased(P<0.01),though overall proliferation rate slowed.During differentiation,the myoblast fusion index significantly decreased(P<0.01).Conclusion Metformin induces metabolic reprogramming in myoblasts and suppresses their proliferation and differentiation,with activation of AMPK-related signaling pathways serving as a key molecular mechanism.
Keywords：myoblastsenergy metabolismmetforminAMP-activated protein kinaseproliferationdifferentiation
Publication Date：2025-06-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 214-219 )