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

Kvido Smitka, Hana Papezova, Karel Vondra, Martin Hill, Vojtech Hainer, Jara Nedvidkova, Kvido Smitka, Hana Papezova, Karel Vondra, Martin Hill, Vojtech Hainer, Jara Nedvidkova

Abstract

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

Figures

Figure 1
Figure 1
The role of adipose tissue- (AT-) gut-brain axis peptides in long-term and short-term regulation of food intake. Long-term regulators are adipose-derived food intake-inhibiting hormone leptin or food intake-stimulating hormone neuropeptide Y (NPY) mainly produced by the hypothalamus and also cosecreted with synthesized catecholamines in AT. Hormones produced in the gut are short-term food intake-stimulating hormone ghrelin, or food intake-inhibiting peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK), insulin, and putative anorexigen obestatin (the hypothalamus (violet), nucleus tractus solitarius (NTS, blue), sympathetic and serotoninergic areas (red), and vagal nerve parasympathetic area (green)).
Figure 2
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].

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Source: PubMed

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