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

Marie François (1, 2) , Swapnali Barde (3) , Romain Legrand (1, 2) , Nicolas Lucas (1, 2) , Saïda Azhar (1, 2) , Mohammed El Dhaybi (1, 2) , Charlène Guérin (1, 2) , Tomas Hökfelt (3) , Pierre Dechelotte (1, 2, 4) , Moïse Coëffier (1, 2, 4) , Sergueï O. Fetissov (2, 1)

1 ADEN - Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau
2 IRIB - Institute for Research and Innovation in Biomedicine
3 Karolinska Institutet [Stockholm]
4 CHU Rouen

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.

Mots clés: High-fat diet; Obesity; Ghrelin; In situ hybridization; Autoantibodies

Domaines: Alimentation et Nutrition

Marie François, Swapnali Barde, Romain Legrand, Nicolas Lucas, Saïda Azhar, et al.. High-fat diet increases ghrelin-expressing cells in stomach, contributing to obesity. Nutrition, 2016, 32 (6), pp.709-715. ⟨10.1016/j.nut.2015.12.034⟩. ⟨hal-02291098⟩