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.

Objective To explore any effect of calorie restriction on the proliferation of satellite cells in the skeletal muscles of elderly rats.Methods Twelve male C57BL rats aged 12 or 13 months were randomly divided in to an experimental group and a control group,each of 6.The control group was fed 75.09 kJ/d as normal,while the experimental group was provided with 45.05 kJ/d (60％ of normal).The intervention lasted for 15 weeks and each rat's weight was measured every week.After the intervention,limb muscle satellite cells were sorted by fluorescenceactivated cell sorting after digestion,and the cell cycle was analyzed.Western blotting was used to assess the expression of cyclin A,D1 and E.Results There was no significant difference in the average weight of the two groups before the experiment.After the 15 weeks the average weight of the experimental group had decreased significantly (to 19.5±0.4 g),and it was significantly lighter than that of the control group (31.9±0.5 g).The average percentage of the satellite cells in the G0/G1 phase had decreased significantly in the experimental group,but the percentage in the S phase had increased significantly.The expression of cyclin A and E was significantly greater in the experimental group compared with the control group,but the expression of cyclin D1 had decreased significantly.Conclusion Caloric restriction can delay the proliferation of satellite cells in the skeletal muscles of elderly mice.