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A new target for leptin

Nature Reviews Neuroscience volume 26, page 2 (2025)Cite this article

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Leptin reduces appetite by altering the activity of certain neuronal populations that express the leptin receptor (LEPR), including agouti-related protein (AGRP)/neuropeptide Y (NPY) neurons (hunger promoting) and pro-opiomelanocortin (POMC) neurons (hunger suppressing) in the arcuate nucleus (ARC). Food intake is thought to be reciprocally regulated by these two sets of neurons; however, their activity alone cannot account for the effects of leptin on body weight, which suggests the existence of other — yet to be defined — leptin-responsive neurons. Now, a study published in Nature has discovered a population of neurons that regulate food intake and mediate leptin action.

The authors performed single-nucleus RNA sequencing (snRNA-seq) of the mouse ARC and identified a neuronal cell cluster — marked by expression of Bnc2 — that expressed LEPR but did not express AGRP/NPY or POMC. Leptin administration or refeeding of mice after fasting resulted in robust activation of these cells, as evidenced by markers of leptin signalling and neuronal activation in fluorescently labelled BNC2 neurons. In vivo calcium imaging confirmed BNC2 neuron activation by feeding and revealed that their activation is further modulated by food palatability, nutritional status and food consumption.

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  1. Nature Reviews Neuroscience http://www.nature.com/nrn/

    Michael Attwaters

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  1. Michael Attwaters
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Correspondence to Michael Attwaters.

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Attwaters, M. A new target for leptin. Nat. Rev. Neurosci. 26, 2 (2025). https://doi.org/10.1038/s41583-024-00884-0

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