title: Altered gastric vagal mechanosensitivity in diet-induced obesity persists on return to normal chow and is accompanied by increased food intake.
abstract: OBJECTIVE
  Gastric vagal afferents convey satiety signals in response to mechanical stimuli. The sensitivity of these afferents is decreased in diet-induced obesity. Leptin, secreted from gastric epithelial cells, potentiates the response of vagal afferents to mechanical stimuli in lean mice, but has an inhibitory effect in high-fat diet (HFD)-induced obese mice. We sought to determine whether changes in vagal afferent function and response to leptin in obesity were reversible by returning obese mice consuming a HFD to standard laboratory chow diet (SLD).
  
  
  METHODS
  Eight-week-old female C57BL/6 mice were either fed a SLD (N=20) or HFD (N=20) for 24 weeks. A third group was fed a HFD for 12 weeks and then a SLD for a further 12 weeks (RFD, N=18). An in vitro gastro-oesophageal vagal afferent preparation was used to determine the mechanosensitivity of gastric vagal afferents and the modulatory effect of leptin (0.1-10 nM) was examined. Retrograde tracing and quantitative RT-PCR were used to determine the expression of leptin receptor (LepR) messenger RNA (mRNA) in whole nodose and specific cell bodies traced from the stomach.
  
  
  RESULTS
  After 24 weeks, both the HFD and RFD mice had increased body weight, gonadal fat mass, plasma leptin, plasma insulin and daily energy consumption compared with the SLD mice. The HFD and RFD mice had reduced tension receptor mechanosensitivity and leptin further inhibited responses to tension in HFD, RFD but not SLD mice. Mucosal receptors from both the SLD and RFD mice were potentiated by leptin, an effect not seen in HFD mice. LepR expression was unchanged in the whole nodose, but was reduced in the mucosal afferents of the HFD and RFD mice.
  
  
  CONCLUSIONS
  Disruption of gastric vagal afferent function by HFD-induced obesity is only partially reversible by dietary change, which provides a potential mechanism preventing maintenance of weight loss.
authors.affiliation: Nerve-Gut Research Laboratory, Hanson Institute, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kentish
authors.affiliation: Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: T A
authors.initials: TA
authors.lastname: O'Donnell
authors.affiliation: Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: C L
authors.initials: CL
authors.lastname: Frisby
authors.affiliation: Nerve-Gut Research Laboratory, Hanson Institute, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Nerve-Gut Research Laboratory, Hanson Institute, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: G A
authors.initials: GA
authors.lastname: Wittert
authors.affiliation: 1] Nerve-Gut Research Laboratory, Hanson Institute, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia [2] Royal Adelaide Hospital, Adelaide, SA, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Page
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat; D002149:Energy Intake; D005247:Feeding Behavior; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000378:metabolism*; D013851:Thinness / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*; D015430:Weight Gain
chemical_list: D020738:Leptin; D054411:Receptors, Leptin
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