Marie François1, Swapnali Barde2, Romain Legrand1, Nicolas Lucas1, Saida Azhar1, Mohammed El Dhaybi1, Charlène Guerin1, Tomas Hökfelt2, Pierre Déchelotte3, Moise Coëffier3, Sergueï O Fetissov4. 1. Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen, France. 2. Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. 3. 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. 4. 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.
Abstract
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.
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.