Emerging role of autoantibodies against appetite-regulating neuropeptides in eating disorders

Objective Recent findings of autoantibodies directed against melanocortin peptides suggest that these autoantibodies may represent a source of variability in peptidergic signaling that can be responsible for altered appetite and emotion in eating disorders. However, it is still unknown if autoantibodies directed against some other appetite-regulating neuropeptides and peptide hormones exist in healthy human subjects and if these autoantibodies can regulate appetite and emotion. Methods We determined the presence of autoantibodies against some key appetite-regulating neuropeptides and peptide hormones in sera of human subjects and in rats, and used animal models to study the role of α-melanocyte-stimulating hormone autoantibodies in food intake and anxiety. Results Immunoglobulin G and A autoantibodies against α-melanocyte-stimulating hormone, neuropeptide Y, agouti-related protein, ghrelin, leptin, and some other neuropeptides or peptide hormones involved in appetite control were present in healthy humans and rats. Animal models including active and passive transfer showed that α-melanocyte-stimulating hormone autoantibodies are involved in the regulation of feeding and anxiety. Sequence homology was found between neuropeptides and proteins from some members of intestinal microflora, whereas germ-free rats showed altered levels of autoantibodies directed against several neuropeptides. Conclusion Autoantibodies directed against appetite-regulating neuropeptides and peptide hormones are emerging as important participants in the peptidergic mechanisms controlling motivated behavior. Furthermore, these autoantibodies could provide a link in the gut–brain axis and may represent new biological targets for the diagnosis and treatment of eating disorders.