Team identifies ion channel necessary for hormone and anti-obesity drug to suppress eating

UTSW identifies ion channel necessary for hormone and anti-obesity drug to suppress eating
(From left) Dr. Yiru Huang, Ting Yao, Dr. Tiemin Liu, Dr. Kevin Williams, and Dr. Jia Sun. Credit: UT Southwestern

UT Southwestern Medical Center researchers have identified an ion channel required for brain cells to suppress eating behavior in response to the hormone leptin or to the anti-obesity drug lorcaserin.

Ion channels are tunnel-shaped passageways on the surface of neurons through which charged particles, or ions, can travel in and out of the cell.

A deeper understanding of this brain-metabolism relationship could someday lead to new, better targeted treatments for obesity or diabetes, said lead author Dr. Kevin Williams, Assistant Professor of Internal Medicine at UT Southwestern and senior author of the study, published recently in Cell Reports.

"We found that an ion channel made up of TrpC5 (transient receptor potential cation 5) protein subunits is required for the proper regulation of basal metabolism and body weight," Dr. Williams said.

In the mouse study, loss of TrpC5 caused types of nerve cells in the brain called Pomc neurons to become unresponsive to leptin or lorcaserin, resulting in increased body weight over time. The normally beneficial effect of lorcaserin on blood-sugar levels was also lost in mice deficient for TrpC5, the study showed.

"As researchers, we are trying to understand the cellular and that contribute to changes in and blood-sugar balance. There is a possibility that this may someday be directly targeted for therapeutic regulation of eating and blood-sugar balance," Dr. Williams said.

Leptin and lorcaserin exert their effects on eating and other aspects of metabolism by binding to different types of receptors that sit on the surface of Pomc neurons in the hypothalamus, the part of the brain that helps govern metabolism and other involuntary bodily functions such as breathing and sleeping. The ion channels, formed when TrpC proteins gather together to form a channel, or tube-like structure, are also on the surface of Pomc neurons.

Although leptin and lorcaserin bind to different receptors, binding is ineffective unless nearby TrpC5 ion channels are opened to allow the passage of ions in and out of the cell.

The researchers conducted experiments comparing normal mice and mice genetically unable to make TrpC5. Energy balance, , and activity levels were measured. The researchers found that a lack of TrpC5 in Pomc neurons was enough to block the usual appetite-suppressing effects of leptin and lorcaserin. Lack of TrpC5 also seemed to blunt the cell's electrophysiological response to leptin and lorcaserin.

The research helps explain some intriguing observations previously made by researchers at UT Southwestern and elsewhere. Studying the seven proteins in the TrpC family, earlier studies determined that TrpC1, TrpC4, and TrpC5 (and to a lesser extent TrpC6 and TrpC7) were detected in Pomc neurons. Although it was known that these TrpC family members could form ion channels, the effects or relative importance of TrpC5 proteins in particular to regulate metabolism were unknown, Dr. Williams said. Moreover, the molecular mechanisms underlying appetite suppression in response to activation of receptors for leptin or lorcaserin were unclear, he added.

"Our results link TrpC5 subunits in the brain with - and lorcaserin-dependent changes in nerve activity as well as , eating behavior, and blood-sugar levels," Dr. Williams said.


Explore further

Improved understanding of appetite-control proteins suggest treatment of obesity

More information: Yong Gao et al, TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons, Cell Reports (2017). DOI: 10.1016/j.celrep.2016.12.072
Journal information: Cell Reports

Citation: Team identifies ion channel necessary for hormone and anti-obesity drug to suppress eating (2017, February 6) retrieved 9 April 2020 from https://medicalxpress.com/news/2017-02-team-ion-channel-hormone-anti-obesity.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
0 shares

Feedback to editors

User comments