Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels
Abstract
Leptin, the protein encoded by the obese (ob) gene, is secreted from adipose tissue and is thought to act in the central nervous system to regulate food intake and body weight. It has been proposed that leptin acts in the hypothalamus, the main control centre for satiety and energy expenditure. Mutations in leptin or the receptor isoform (Ob-R[L]) present in hypothalamic neurons result in profound obesity and symptoms of non-insulin-dependent diabetes. Here we show that leptin hyperpolarizes glucose-receptive hypothalamic neurons of lean Sprague-Dawley and Zucker rats, but is ineffective on neurons of obese Zucker (fa/fa) rats. This hyperpolarization is due to the activation of a potassium current, and is not easily recovered on removal of leptin, but is reversed by applying the sulphonylurea, tolbutamide. Single-channel recordings demonstrate that leptin activates an ATP-sensitive potassium (K[ATP]) channel. Our data indicate that the K(ATP) channel may function as the molecular end-point of the pathway following leptin activation of the Ob-R(L) receptor in hypothalamic neurons.
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Leptin rapidly changes the membrane potential and firing rate of hypothalamic neurons in electrophysiological studies.
“in electrophysiological studies using freshly prepared hypothalamic slices, leptin rapidly changes the membrane potential and firing rate of neurons (42, 176)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [176]
Leptin and insulin hyperpolarize a subset of glucose-responsive neurons in the ARC via activation of KATP channels, a mechanism blocked by a PI3K inhibitor.
“leptin and insulin were shown to hyperpolarize a subset of “glucose-responsive” neurons in the ARC via activation of the ATP-sensitive potassium channel (KATP) (176, 177) via a mechanism that was blocked by a PI3K inhibitor (116, 177).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [176]
Insulin and leptin activate ATP-sensitive potassium channels and hyperpolarize a subset of glucose-responsive neurons via a mechanism requiring PI3K.
“both insulin and leptin activate ATP-sensitive potassium channels and thereby hyperpolarize a subset of “glucose-responsive” neurons via a mechanism that requires PI3K (176, 177).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [176]
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- Authors
- Spanswick, D., Smith, M. A., Groppi, V. E., Logan, S. D., & Ashford, M. L. J.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Ashford, M. L. J.
- Venue
- Nature
- Published
- 1997-12
- Volume
- 390
- Issue
- 6659
- Pages
- 521-525
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1623365227
- Cited by
- 628
- References
- 29
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 5 · 2023: 9 · 2022: 6 · 2021: 13 · 2020: 10 · 2019: 9 · 2018: 16 · 2017: 17 · 2016: 9 · 2015: 15 · 2014: 22 · 2013: 21 · 2012: 26
- FWCI
- 9.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Wellcome Trust
- University of Aberdeen
- 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 › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, ATP-sensitive potassium channels, hypothalamic neurons, glucose receptor, neuronal hyperpolarization, potassium currents, tolbutamide, sulfonylureas, obesity, Zucker rats, food intake regulation, satiety, energy expenditure
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Membrane, Electrophysiology, Glucose, Hypoglycemic Agents, Hypothalamus, Neurons, Obesity, Proteins, Rats, Zucker, Tolbutamide, Potassium Channels, Rats, Sprague-Dawley, Leptin, Rats, In Vitro Techniques
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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