Rapid, reversible activation of AgRP neurons drives feeding behavior in mice

Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designe...

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Bibliographic Details
Published in:	The Journal of clinical investigation Vol. 121; no. 4; pp. 1424 - 1428
Main Authors:	Krashes, Michael J, Koda, Shuichi, Ye, ChianPing, Rogan, Sarah C, Adams, Andrew C, Cusher, Daniel S, Maratos-Flier, Eleftheria, Roth, Bryan L, Lowell, Bradford B
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 01-04-2011
Subjects:	Ablation Agouti-Related Protein - genetics Agouti-Related Protein - physiology Animal feeding behavior Animals Arcuate Nucleus of Hypothalamus - drug effects Arcuate Nucleus of Hypothalamus - physiology Biomedical research Brain - drug effects Brain - physiology Brief Report Cardiovascular diseases Clozapine - analogs & derivatives Clozapine - pharmacology Complications and side effects Eating - physiology Energy Energy Metabolism Feeding Behavior - drug effects Feeding Behavior - physiology Female Genetic aspects Health aspects Homeostasis Hypothalamus Male Mice Mice, Transgenic Nerve proteins Neurons Neurons - drug effects Neurons - physiology Obesity Properties Proteins Risk factors Weight Gain - drug effects Weight Gain - physiology United States
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Summary:	Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the evidence supporting this view is incomplete. Using designer receptors exclusively activated by designer drugs (DREADD) technology to provide specific and reversible regulation of neuronal activity in mice, we have demonstrated that acute activation of AgRP neurons rapidly and dramatically induces feeding, reduces energy expenditure, and ultimately increases fat stores. All these effects returned to baseline after stimulation was withdrawn. In contrast, inhibiting AgRP neuronal activity in hungry mice reduced food intake. Together, these findings demonstrate that AgRP neuron activity is both necessary and sufficient for feeding. Of interest, activating AgRP neurons potently increased motivation for feeding and also drove intense food-seeking behavior, demonstrating that AgRP neurons engage brain sites controlling multiple levels of feeding behavior. Due to its ease of use and suitability for both acute and chronic regulation, DREADD technology is ideally suited for investigating the neural circuits hypothesized to regulate energy balance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: Michael J. Krashes and Shuichi Koda contributed equally to this work.
ISSN:	0021-9738 1558-8238
DOI:	10.1172/jci46229