Objective To explore the correlation between hypothalamic sympathetic hyperresponsiveness and peripheral lipid metabolism change after traumatic brain injuries(TBI),and to shed light on nutritional manage-ment for severe TBI.Methods Eight-week C57BL/6 mice were randomly divided into Sham group,TBI-1 d group,TBI-3 d group,and TBI-7 d group,with 6 mice in each group.Mice in the TBI groups experienced a heavy object strike,while those in the Sham group only underwent scalp incision and suture.Mice were executed and sampled at the corresponding time points.The lipid droplets of the liver and the brown adipose tissue were identified by oil-red staining and immunofluorescence staining;the change of liver lipophagy in different groups was detected through Western blot;the activation of neurons in the hypothalamus,raphe nuclei and rostral ventrolateral medulla was de-tected by c-Fos immunofluorescence staining;and the molecular level changes in energy metabolism-related neurons in the hypothalamic region after TBI were identified by analyzing single-cell data.Results(1)The size of lipid droplets in brown adipose tissue decreased significantly after TBI,and the cell density of brown adipose tissue in-creased in TBI groups,compared with the Sham group.(2)Oil red staining showed a slight increase in liver lipid droplets after TBI;meanwhile,fluorescence staining indicated an increase in perilipin-2(PLIN2)positive particles after TBI.An elevation in liver lipophagy-related proteins after TBI was detected through Western blot,indicating a boost in liver lipid utilization ability.(3)The c-Fos fluorescence staining in the hypothalamus,raphe nuclei and rostral ventrolateral medulla oblongata revealed that the number of activated neurons increased after TBI.(4)Sin-gle-cell results showed significant signal changes in hormone regulation,energy metabolism,and excitatory neuronal activity in the hypothalamic neurons after TBI.Conclusion Activation of neurons in the hypothalamus/medulla af-ter TBI may be related to sympathetic hyperresponsiveness,thus promoting the lipid metabolism of brown adipose tis-sue and liver.