Emerging role of autoantibodies against appetite-regulating
neuropeptides in eating disorders.
Fetissov SO, Hamze Sinno M, Coquerel Q, Do Rego JC, Coeffier M, Gilbert
D, Hokfelt T, Dechelotte P.
Digestive System and Nutrition Laboratory (ADEN EA3234), Institute of
Biomedical Research, Rouen University, IFR23, Rouen, France.

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 alpha-melanocyte-stimulating hormone autoantibodies in food intake
and anxiety. RESULTS: Immunoglobulin G and A autoantibodies against
alpha-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
alpha-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.

Publication Types:
*  Research Support, Non-U.S. Gov't
*  Review

Autoantibodies against appetite-regulating peptide hormones and
neuropeptides: putative modulation by gut microflora.
Fetissov SO, Hamze Sinno M, Coeffier M, Bole-Feysot C, Ducrotte P,
Hokfelt T, Dechelotte P.
Digestive System and Nutrition Laboratory (ADEN EA3234), Institute of
Biomedical Research, Rouen University and Hospital, IFRMP23, Rouen,
France.

OBJECTIVE: Peptide hormones synthesized in gastrointestinal and adipose
tissues in addition to neuropeptides regulate appetite and body weight.
Previously, autoantibodies directed against melanocortin peptides were
found in patients with eating disorders; however, it remains unknown
whether autoantibodies directed against other appetite-regulating
peptides are present in human sera and whether their levels are
influenced by gut-related antigens. METHODS: Healthy women were studied
for the presence of immunoglobulin (Ig) G and IgA autoantibodies
directed against 14 key appetite-regulating peptides. The concept of
molecular mimicry was applied to search in silico whether bacteria,
viruses, or fungi contain proteins with amino acid sequences identical
to appetite-regulating peptides. In addition, autoantibodies serum
levels were studied in germ-free and specific pathogen-free rats.
RESULTS: We found these IgG and IgA autoantibodies directed against
leptin, ghrelin, peptide YY, neuropeptide Y, and other
appetite-regulating peptides are present in human sera at levels of
100-900 ng/mL. Numerous cases of sequence homology with these peptides
were identified among commensal and pathogenic micro-organisms including
Lactobacilli, bacteroides, Helicobacter pylori, Escherichia coli, and
Candida species. Decreased levels of IgA autoantibodies directed against
several appetite-regulating peptides and increased levels of antighrelin
IgG were found in germ-free rats compared with specific pathogen-free
rats. CONCLUSION: Healthy humans and rats display autoantibodies
directed against appetite-regulating peptide hormones and neuropeptides,
suggesting that these autoantibodies may have physiologic implications
in hunger and satiety pathways. Gut-related antigens including the
intestinal microflora may influence production of theses autoantibodies,
suggesting a new link between the gut and appetite control.

Publication Types:
*  Research Support, Non-U.S. Gov't