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Nat Commun ; 15(1): 3443, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658557

RESUMO

The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of 'Ghost' neurons endowed with atypical molecular and functional identity. Compared to 'classical' Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are 'invisible' to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.


Assuntos
Hipotálamo , Neurônios , Obesidade , Pró-Opiomelanocortina , Análise de Célula Única , Animais , Pró-Opiomelanocortina/metabolismo , Pró-Opiomelanocortina/genética , Neurônios/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Masculino , Camundongos , Hipotálamo/metabolismo , Hipotálamo/citologia , Modelos Animais de Doenças , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese , Camundongos Obesos
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