Single-cell multi-omics identify OTP and NOVA1 as regulators of leptin action in hypothalamic feeding circuits

Leptin reshapes single-neuron transcription and chromatin states in arcuate nucleus and paraventricular hypothalamic nucleus circuits of ob/ob mice, propagating hierarchically from ARC to PVH.

• Why it matters: How one circulating hormone coordinates molecular programs across multiple hypothalamic neuronal populations and circuits is still unclear.
• What they did: The study combined time-resolved single-nucleus transcriptomics with chromatin accessibility profiling in leptin-treated ob/ob mice, then integrated RNA velocity, cis-regulatory analysis, and cell-cell communication inference.
• The result: OTP in AGRP neurons mediates leptin inhibition of hunger-promoting AGRP activity and feeding, while leptin-regulated NOVA1 in PVH neurons bidirectionally controls food intake and body weight.

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