Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity

Guillaume de Lartigue, Charlotte C. Ronveaux, Helen E Raybould

Research output: Contribution to journalArticle

47 Citations (Scopus)

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/LepRfl/fl mice). Chow fed Nav1.8/LepRfl/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/LepRfl/fl mice; energy expenditure was unaltered. Reduced satiation in Nav1.8/LepRfl/fl mice is in part due to reduced sensitivity of VAN to CCK and the subsequent loss of VAN plasticity. Crucially Nav1.8/LepRl/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.

Original languageEnglish (US)
Pages (from-to)595-607
Number of pages13
JournalMolecular Metabolism
Volume3
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Afferent Neurons
Hyperphagia
Leptin
Obesity
Meals
Satiation
Afferent Pathways
Leptin Receptors
Adiposity
High Fat Diet
Sensory Receptor Cells
Knockout Mice
Energy Metabolism
Weight Gain
Cues
Eating
Hormones
Brain

Keywords

  • High fat diet
  • Hyperphagy
  • Leptin
  • Meal pattern
  • Obesity
  • Vagus nerve

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity. / de Lartigue, Guillaume; Ronveaux, Charlotte C.; Raybould, Helen E.

In: Molecular Metabolism, Vol. 3, No. 6, 2014, p. 595-607.

Research output: Contribution to journalArticle

de Lartigue, Guillaume ; Ronveaux, Charlotte C. ; Raybould, Helen E. / Deletion of leptin signaling in vagal afferent neurons results in hyperphagia and obesity. In: Molecular Metabolism. 2014 ; Vol. 3, No. 6. pp. 595-607.
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