Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans

Abstract

Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin’s orexigenic effect, which may contribute to increased appetite and overeating. Obesity is often associated with increased appetite and food intake, despite normal blood levels of the hunger hormone ghrelin. Here the authors show that ghrelin-reactive antibodies in the blood of obese mice and humans enhance the orexigenic effect of ghrelin by protecting it from degradation.