High-fat diet increases ghrelin-expressing cells in stomach, contributing to obesity

Nutrition. 2016 Jun;32(6):709-15. doi: 10.1016/j.nut.2015.12.034. Epub 2015 Dec 30.


Objectives: 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.

Conclusion: 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.

Keywords: Autoantibodies; Ghrelin; High-fat diet; In situ hybridization; Obesity.

MeSH terms

  • Animals
  • Diet, High-Fat*
  • Disease Models, Animal
  • Gastric Mucosa / metabolism*
  • Ghrelin / blood*
  • Immunoglobulin G / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / blood*
  • RNA, Messenger / blood


  • Ghrelin
  • Immunoglobulin G
  • RNA, Messenger