Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/79659
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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: Journal of Physiology-London, 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
RMID: 0020126549
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:Medicine publications

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