title: High-fat diet increases ghrelin-expressing cells in stomach, contributing to obesity.
abstract: OBJECTIVE
  Mechanisms of high-fat diet (HFD)-induced obesity may involve ghrelin, an orexigenic and adipogenic hormone secreted by the stomach. Previous studies showed that obese subjects may display higher numbers of ghrelin-producing cells and increased affinity of plasma immunoglobulins (Ig) for ghrelin, protecting it from degradation. The aim of this study was to determine if a HFD in mice would increase the number of ghrelin-expressing cells and affinity of ghrelin-reactive IgG.
  
  
  METHODS
  Obesity in mice was induced by consumption of a 13-wk HFD. The number of preproghrelin mRNA-expressing cells in the stomach was analyzed by in situ hybridization and compared with chow-fed, nonobese controls and with genetically obese ob/ob mice. Affinity of ghrelin-reactive IgG was analyzed using surface plasmon resonance. Plasma levels of ghrelin and des-acyl ghrelin were measured.
  
  
  RESULTS
  HFD resulted in 30% of body fat content versus only 8% in controls (P < 0.001). The number of preproghrelin mRNA-producing cells was 15% (P < 0.05) higher in HFD-fed mice than in controls, contrasting with ob/ob mice, having a 41% (P < 0.001) decrease. Both models of obesity had normal plasma levels of ghrelin but a decrease of its des-acylated form. Ghrelin-reactive IgG affinity was found in the micromolar range with mean values of the dissociation equilibrium constant 1.5-fold (P < 0.05) lower in HFD-fed versus control mice.
  
  
  CONCLUSIONS
  Results from the present study showed that HFD in mice induces obesogenic changes, including increased numbers of ghrelin precursor-expressing cells and increased affinity of ghrelin-reactive IgG. Such changes may contribute to the mechanisms of HFD-induced obesity.
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Marie
authors: M
authors: François
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Swapnali
authors: S
authors: Barde
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Romain
authors: R
authors: Legrand
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Nicolas
authors: N
authors: Lucas
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Saida
authors: S
authors: Azhar
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Mohammed
authors: M
authors: El Dhaybi
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France.
authors: Charlène
authors: C
authors: Guerin
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Tomas
authors: T
authors: Hökfelt
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France; Rouen University Hospital, CHU Charles Nicolle, Rouen, France.
authors: Pierre
authors: P
authors: Déchelotte
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France; Rouen University Hospital, CHU Charles Nicolle, Rouen, France.
authors: Moise
authors: M
authors: Coëffier
authors: Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France. Electronic address: Serguei.Fetissov@univ-rouen.fr.
authors: Sergueï O
authors: SO
authors: Fetissov
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood
chemical_list: D054439:Ghrelin; D007074:Immunoglobulin G; D012333:RNA, Messenger
keywords: Autoantibodies; Ghrelin; High-fat diet; In situ hybridization; Obesity