Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/79659
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Gastric vagal afferent modulation by leptin is influenced by food intake status |
Author: | Kentish, S. O'Donnell, T. Isaacs, N. Young, R. Li, H. Harrington, A. Brierley, S. Wittert, G. Blackshaw, L. Page, A. |
Citation: | The Journal of Physiology, 2013; 591(7):1921-1934 |
Publisher: | Blackwell Publishing Ltd |
Issue Date: | 2013 |
ISSN: | 0022-3751 1469-7793 |
Statement of Responsibility: | Stephen J. Kentish, Tracey A. O’Donnell, Nicole J. Isaacs, Richard L. Young, Hui Li, Andrea M. Harrington, Stuart M. Brierley, Gary A. Wittert, L. Ashley Blackshaw and Amanda J. Page |
Abstract: | Energy intake is strongly influenced by vagal afferent signals from the stomach, and is also modulated by leptin. Leptin may be secreted from gastric epithelial cells, so we aimed to determine the direct effect of leptin on gastric vagal afferents under different feeding conditions. Female C57BL/6 mice were fed standard laboratory diet, high-fat diet or were food restricted. The expression of leptin receptor (Lep-R) and its signal transduction molecules in vagal afferents was determined by retrograde tracing and reverse-transcription polymerase chain reaction, and the relationship between leptin-immunopositive cells and gastric vagal afferent endings determined by anterograde tracing and leptin immunohistochemistry. An in vitro preparation was used to determine the functional effects of leptin on gastric vagal afferents and the second messenger pathways involved. Leptin potentiated vagal mucosal afferent responses to tactile stimuli, and epithelial cells expressing leptin were found close to vagal mucosal endings. After fasting or diet-induced obesity, potentiation of mucosal afferents by leptin was lost and Lep-R expression reduced in the cell bodies of gastric mucosal afferents. These effects in diet-induced obese mice were accompanied by a reduction in anatomical vagal innervation of the gastric mucosa. In striking contrast, after fasting or diet-induced obesity, leptin actually inhibited responses to distension in tension receptors. The inhibitory effect on gastric tension receptors was mediated through phosphatidylinositol 3-kinase-dependent activation of large-conductance calcium-activated potassium channels. The excitatory effect of leptin on gastric mucosal vagal afferents was mediated by phospholipase C-dependent activation of canonical transient receptor potential channels. These data suggest the effect of leptin on gastric vagal afferent excitability is dynamic and related to the feeding state. Paradoxically, in obesity, leptin may reduce responses to gastric distension following food intake. |
Keywords: | Muscle, Smooth Gastric Mucosa Nodose Ganglion Vagus Nerve Animals Mice, Inbred C57BL Mice Obesity Leptin Eating Female Receptors, Leptin Diet, High-Fat |
Rights: | © 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society |
DOI: | 10.1113/jphysiol.2012.247577 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/565186 |
Published version: | http://onlinelibrary.wiley.com.proxy.library.adelaide.edu.au/doi/10.1113/jphysiol.2012.247577/abstract |
Appears in Collections: | Aurora harvest Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.