Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons

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Neuropeptide Y (NPY) stimulates food intake and promotes weight gain, whereas melanocortins have the opposite effect. Yet both peptides are synthesized in the arcuate nucleus, a hypothalamic area involved in energy homeostasis. We report here that mRNA encoding NPY and the melanocortin precursor, proopiomelanocortin (POMC) are expressed in adjacent, but distinct, subpopulations of arcuate nucleus neurons. Moreover, these NPY neurons coexpress mRNA encoding Agouti-related protein (Agrp), an endogenous melanocortin receptor antagonist, and fasting increases the expression of both of these mRNA species. Our findings suggest that hypothalamic NPY/Agrp neurons constitute a unique cell type that is activated by fasting to stimulate food intake via a simultaneous increase of NPY and decrease of melanocortin.

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Figure 1: Fluorescent in situ hybridization of mRNA encoding Agrp in the ARC of mice fed ad libitum (a) or fasted (b).
Figure 2: Colocalization of Agrp, NPY and POMC mRNA.
Figure 3: Colocalization of Agrp with NPY and POMC mRNA in rat arcuate nucleus.


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We thank S. Fisher in the Department of Metabolic Diseases at Hoffmann LaRoche, Inc for sequencing the murine Agrp clones and Daniel Porte, Jr. for his helpful comments. This work was supported by grants from the NIH (DK-12829, DK-52989 and NS-32273), the Diabetes Endocrinology Research Center and Clinical Nutrition Research Unit at the University of Washington, the VA Merit Review program, and the Metabolic Diseases Unit, Hoffmann LaRoche.

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Correspondence to Michael W. Schwartz.

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