Rapid, reversible activation of AgRP neurons drives feeding behavior in mice
Open accessAbstract
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 All these effects returned to baseline after stimulation was withdrawn.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.
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Melanin-concentrating hormone promotes food consumption by acting directly on the lateral nucleus of the hypothalamus.
“Melanin-concentrating hormone (MCH) promotes food consumption by acting directly on the lateral nucleus of the hypothalamus.”
From Estrogen deficiency and the origin of obesity during menopause (2014) · cites this paper as [100]
AgRP neurons in the arcuate nucleus are essential for maintaining energy balance, and their activity rapidly drives feeding in hunger.
“Specifically, the agouti-related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are essential in the maintenance of energy balance, and their activity rapidly drives feeding behavior in a state of hunger173.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [173]
AgRP neurons are activated in energy deficit, and their optical stimulation promotes food consumption but also elicits real-time place avoidance in the absence of food.
“AgRP neurons are activated in a state of energy deficit228, and their optical stimulation can voraciously promote food consumption, but also elicits real-time place avoidance (indicative of an aversive state) in the absence of food173,227,229.”
From Neural mechanisms of social homeostasis (2019) · cites this paper as [173]
Optogenetic and chemogenetic activation of AgRP neurons can evoke feeding in fed mice and promote motivationally, food-seeking behavior.
“Optogenetic and chemogenetic activation of AgRP neurons can evoke feeding in fed mice and promote motivationally, food-seeking behavior [26, 27].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [27]
Inhibition of AgRP neurons suppresses feeding.
“Conversely, inhibition of these neurons suppresses feeding [27].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [27]
AgRP neurons in the ARC of the hypothalamus contribute to reward-driven feeding and food-seeking behavior.
“A number of studies have shown that AgRP neurons in the ARC of the hypothalamus contribute to reward-driven feeding [28] and food-seeking behavior [26, 27].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [27]
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- Authors
- Krashes, M. J., Koda, S., Ye, C., Rogan, S. C., Adams, A. C., Cusher, D. S., Maratos-Flier, E., Roth, B. L., & Lowell, B. B.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Lowell, Bradford B.
- Venue
- Journal of Clinical Investigation
- Published
- 2011-04-01
- Volume
- 121
- Issue
- 4
- Pages
- 1424-1428
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3069789
- OpenAlex
- W2069072617
- Cited by
- 1,578
- References
- 22
- Citations by year
- 2026: 91 · 2025: 150 · 2024: 143 · 2023: 135 · 2022: 116 · 2021: 148 · 2020: 128 · 2019: 119 · 2018: 101 · 2017: 110 · 2016: 92 · 2015: 85 · 2014: 65 · 2013: 49 · 2012: 34
- FWCI
- 23.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Triangle Community Foundation
- National Institutes of Health (5r01dk069983-05)
- National Institute of Mental Health (U19MH082441, U19-MH82441, MH087074, R01MH061887, R01MH61887, F30MH087074)
- National Institute on Drug Abuse (R01DA017204, R01DA027120)
- National Institute of General Medical Sciences (T32GM008719, GM008719)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075632, R01DK089044, R01DK071051, R01-DK-069983, F32DK089710, R37DK053477)
- National Institute of Neurological Disorders and Stroke (NS064882)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- AgRP neurons, agouti-related protein, feeding behavior, energy homeostasis, DREADD, designer receptors, neuronal activation, dietary intake, energy expenditure, fat stores, food-seeking behavior, food motivation
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Brain, Clozapine, Eating, Energy Metabolism, Feeding Behavior, Female, Male, Mice, Transgenic, Neurons, Weight Gain, Mice, Agouti-Related Protein
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