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Publication
Deletion of leptin signaling in vagal afferent neurons results in hyperphagia
and obesity.
Authors de Lartigue G, Ronveaux CC, Raybould HE
Submitted By Helen Raybould on 9/9/2014
Status Published
Journal Molecular metabolism
Year 2014
Date Published
Volume : Pages 3 : 595 - 607
PubMed Reference 25161883
Abstract The vagal afferent pathway senses hormones released from the gut in response to
nutritional cues and relays these signals to the brain. We tested the hypothesis
that leptin resistance in vagal afferent neurons (VAN) is responsible for the
onset of hyperphagia by developing a novel conditional knockout mouse to delete
leptin receptor selectively in sensory neurons (Nav1.8/LepR (fl/fl) mice). Chow
fed Nav1.8/LepR (fl/fl) mice weighed significantly more and had increased
adiposity compared with wildtype mice. Cumulative food intake, meal size, and
meal duration in the dark phase were increased in Nav1.8/LepR (fl/fl) mice;
energy expenditure was unaltered. Reduced satiation in Nav1.8/LepR (fl/fl) mice
is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of
VAN plasticity. Crucially Nav1.8/LepR (l/fl) mice did not gain further weight in
response to a high fat diet. We conclude that disruption of leptin signaling in
VAN is sufficient and necessary to promote hyperphagia and obesity.




Strains
StrainDevelopment StatusCreation MethodOptions
B6.129P2-Leprtm1Rck/JPhenotyping ongoingknockin
View
B6.129-Leprtm1Rck Scn10atm2(cre)JnwPhenotyping ongoingNot specified
View




Genes
SymbolDescription
Leprleptin receptor
Scn10asodium channel, voltage-gated, type X, alpha polypeptide

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