To Eat Or Not To Eat?: How Neuronal Potassium Channel Activi

To eat or not to eat: what inputs to the brain help us make this decision? In a study appearing online in June in advance of print publication in the July issue of the Journal of Clinical Investigation, Jens Bruning and colleagues from the University of Cologne investigate the complex answer to this question.

Two types of neurons in the hypothalamus appear to be the chiefs of appetite regulation - the so-called NYP neurons trigger the feeling of hunger and the POMC neurons inhibit it. The activity of each depends on what chemicals these neurons interact with. The hormones leptin and insulin are two such fuel-sensing chemicals and the intracellular pathways via which they signal intersect at an enzyme known as PI3K, which produces the messenger protein PIP3.

Bruning and colleagues examined the role of PIP3-mediated signals in hypothalamic POMC neurons by inactivating the gene for the PIP3 phosphatase Pten in these cells in mice. This resulted in an excessive ingestion of food beyond what was needed by these animals and diet-induced obesity. Leptin administration failed to significantly inhibit food intake. Interestingly, POMC neurons showed a reduced firing rate that was determined to be due to increased activity of ATP-sensitive potassium channels (KATP channels). The results of this study indicate that KATP channel activity in POMC neurons plays a critical role in regulating POMC activity and consequently the inhibition of the sensation of hunger. Further exploration of this signaling pathway may help to define novel approaches to the treatment of obesity and diabetes.

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TITLE: Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity

AUTHOR CONTACT:
Jens C. Br黱ing
University of Cologne, Cologne, Germany.
E-mail: jens.bruening@uni-koeln.de.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=27123

Contact: Brooke Grindlinger
Journal of Clinical Investigation
(责任编辑：泉水)

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To Eat Or Not To Eat?: How Neuronal Potassium Channel Activi