A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism
Open accessAbstract
Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism.
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AgRP neurons express high levels of SK channels.
“AgRP neurons express high levels of SK channels [82].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [82]
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References 42 · Cited by 34
- Authors
- He, Y., Shu, G., Yang, Y., Xu, P., Xia, Y., Wang, C., Saito, K., Hinton, A., Yan, X., Liu, C., Wu, Q., Tong, Q., & Xu, Y.
- Affiliations
- Baylor College of Medicine (US)
- South China Agricultural University (CN)
- The University of Texas Southwestern Medical Center (US)
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Corresponding author
- Xu, Yong
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 7
- Pages
- 1807-1818
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6248907
- OpenAlex
- W2556906832
- Cited by
- 34
- References
- 42
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 8 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- NIH (R01DK093587, R01DK101379, R01DK092605)
- American Diabetes Association (7-13-JF-61, 1-15-BS-184)
- American Heart Association (13POST13800000, 15POST22670017)
- Davis Foundation
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- SK3, potassium currents, feeding behavior, energy metabolism, food deprivation, satiety, diet-induced obesity, hyperphagia, energy expenditure, energy homeostasis
- MeSH terms
- Action Potentials, Animals, Circadian Rhythm, Energy Metabolism, Fasting, Feeding Behavior, Hyperphagia, Mice, Inbred C57BL, Mutation, Neurons, Neuropeptide Y, Obesity, Ion Channel Gating, N-Methylaspartate, Small-Conductance Calcium-Activated Potassium Channels, Agouti-Related Protein, Diet, High-Fat
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