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Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9489-E9498. doi: 10.1073/pnas.1802237115. Epub 2018 Sep 17.

Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.

Author information

1
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109.
2
Department of Biological Sciences, Columbia University, New York, NY 10027.
3
Department of Bioengineering, Stanford University, Stanford, CA 94305.
4
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109; akil@umich.edu.

Abstract

Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.

KEYWORDS:

agouti-related protein; arcuate nucleus; feeding; proopiomelanocortin; satiety

PMID:
30224492
PMCID:
PMC6176613
DOI:
10.1073/pnas.1802237115
[Indexed for MEDLINE]
Free PMC Article

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