The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

Figure 2

The role of up- or downregulated neutralizing autoantibodies (immunoglobulin (Ig) M, IgG, and IgA classes, and changes of their affinity) directed against appetite-regulating neuropeptides and peptides and neurotransmitters (dopamine, dopamine-beta-hydroxylase, and serotonin) in neuropeptidergic transmission and the pathogenesis of eating disorders. Producing excess of free fatty acids (FFA) and ketones to increase the permeability of the blood-brain barrier and to enter the cerebral matter in AN and BN [103]. Starvation, stress, catecholamines, microbial antigens, poststreptococcal autoimmune process (PANDAS), and proinflammatory cytokines decrease blood-brain barrier integrity in parallel with decreased levels of the tight junction protein, occludin [104]. Also autoantibodies against appetite-regulating peptides and neurotransmitters may disrupt the blood-brain barrier and the gut-barrier permeability in AN and BN [268]. Furthermore, gut-related antigens including gut microflora may influence production of specific autoantibodies (IgA class) against appetite-regulating hormones [47]. Indeed, starvation decreases the gut-barrier permeability in AN [102] and may decrease ghrelin autoantibodies (IgM, IgG, and IgA classes) production. However, realimentation-induced changes in the gut-barrier permeability and new antigenic stimulation during refeeding were accompanied by an increase of acylated ghrelin autoantibodies (IgM class) in AN [48].