biostudies-literatureUnknownKindel MNIDDK NIH HHSNINDS NIH HHSRepeated exercise produces robust physiological benefits and is the leading lifestyle intervention for human health. The benefits from exercise training result from the remodeling of skeletomuscular, cardiovascular, metabolic, and endocrine systems. In mice, we find that activation of the central nervous system following exercise is essential for subsequent endurance performance and metabolism benefits. Ventromedial hypothalamic steroidogenic factor-1 (SF1) neurons are activated following exercise, and repeated training results in increased post-exercise SF1 neuron activation. Exercise training increases the intrinsic excitability and density of excitatory synapses on SF1 neurons, suggesting that exercise history is encoded through hypothalamic plasticity. Inhibition of SF1 neuron output bNeuronS0896-6273(25)00989-4https://www.ebi.ac.uk/biostudies/studies/S-EPMC12912778biostudies-literatureExercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance.PMC12912778R01 DK134857R01 NS134976R01 DK124801R01 DK114104R01 DK133399Thaiss CAWilliams KWKindel MVillari RGoldstein NBetley JNRai MElmquist JKBloss EBKern HCWasserman DHFujikawa THwang EDohnalova LYeung ALo ERichie LLepeak LSkelly BGrose KGolub JCarty JREPost RJLantier LAyala JEfalseExercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance.Repeated exercise produces robust physiological benefits and is the leading lifestyle intervention for human health. The benefits from exercise training result from the remodeling of skeletomuscular, cardiovascular, metabolic, and endocrine systems. In mice, we find that activation of the central nervous system following exercise is essential for subsequent endurance performance and metabolism benefits. Ventromedial hypothalamic steroidogenic factor-1 (SF1) neurons are activated following exercise, and repeated training results in increased post-exercise SF1 neuron activation. Exercise training increases the intrinsic excitability and density of excitatory synapses on SF1 neurons, suggesting that exercise history is encoded through hypothalamic plasticity. Inhibition of SF1 neuron output b2026-01-01T00:00:00Z2026 Feb2026-07-16T00:43:00.199Z2026-07-09T10:26:26.654ZS-EPMC129127784168761210.1016/j.neuron.2025.12.033