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The leptin-melanocortin pathway plays a key role in the control of food intake and body weight. In the brain, pro-opiomelanocortin (POMC) expression is localized to neurons in the arcuate nucleus (ARC) of the hypothalamus and in the nucleus of the solitary tract. POMC is a pro-peptide that is processed to a range of bioactive peptide products. In the ARC, anorexigenic POMC neurons exist alongside orexigenic neurons that express the endogenous melanocortin antagonist agouti-related peptide (AgRP). The canonical view of the melanocortin pathway is one in which leptin, which is produced from white adipose tissue to reflect fat mass, signals to leptin receptors on the POMC and AgRP neurons, increasing the activity of POMC neurons and reducing the activity of AgRP expressing neurons. However, there is a body of evidence that indicates this view of the leptin-melanocortin pathway is over-simplistic. Lam et al. report the results of single cell RNA sequencing in isolated POMC expressing neurons of the arcuate nucleus, which has revealed a previously unappreciated degree of heterogeneity within this anatomically highly localized population. They determined the transcriptomes of 163 individual murine POMC neurons. Unexpectedly, 25% of POMC positive neurons also express high levels of AgRP. The data generated here will be of utility to better understand the fundamental nature of regulation of energy balance by the hypothalamus and to manipulate these systems for therapeutic benefit.

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In this section authors briefly report on their work recently published in Molecular Metabolism.

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Flaminia Fanelli
University of Bologna, Italy
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