Autoantibodies against -MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients

Departments of Neuroscience and Endocrinology, Karolinska Institute, SE-171 77 Stockholm, Sweden.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 01/2003; 99(26):17155-60. DOI: 10.1073/pnas.222658699
Source: PubMed


The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing alpha-melanocyte-stimulating hormone (alpha-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN andor BN patients studied had in their plasma Abs that bind to melanotropes andor corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to alpha-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with alpha-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with alpha-MSH or adrenocorticotropic hormone. Additionally, 3 ANBN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to ANBN staining. These data provide evidence that a significant subpopulation of ANBN patients have autoantibodies that bind to alpha-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitryLHRH system andor in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to andor could be involved in the pathophysiology or clinical presentation of ANBN, and to what extent increased stress is an important factor for production of these autoantibodies.

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Available from: Britt Af Klinteberg, Oct 07, 2015
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    • "This may not be surprising considering different functional role of ␣-MSH-target neurons as well as different ␣-MSH-ergic innervation of these regions. Indeed, while ␣- MSH-immunopositive nerve terminals abundantly innervate the dorsomedial hypothalamus and the perifornical region of the LHA (Fetissov et al., 2002), they are rarely detectable in the NAc, in spite of dense expression of the MC4R in the ventral striatum (Cui et al., 2012a; Hsu et al., 2005). These differences indicate that ␣-MSH should be able to immediately activate local target neurons in the LHA, while in the NAc, ␣-MSH must be delivered by the volume transmission (Fuxe et al., 2013) diffusing from other brain regions or from the peripheral circulation and may play a role of a modulator of the dopaminergic signaling (Lim et al., 2012). "
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    ABSTRACT: α-Melanocyte-stimulating hormone (α-MSH), is a hypothalamic neuropeptide signaling satiation, but it is not known if α-MSH may stimulate dopamine release in a feeding control brain region of the lateral hypothalamic area (LHA), during the anticipatory and consummatory phases of feeding behavior. To address these questions, dynamics of dopamine release were measured in 15min microdialysis samples simultaneously from the LHA and the nucleus accumbens (NAc) during consecutive exposure and provision of food and 1% sucrose in Wistar rats after overnight food deprivation. α-MSH was infused via the microdialysis probe either into the LHA or NAc starting before food exposure. Food, sucrose and water intakes were automatically monitored and analyzed concomitantly with microdialysis samples. We found that LHA-α-MSH-infused rats stopped eating earlier and consumed less food and sucrose as compared to control and NAc-α-MSH-infused rats. Exposure to food produced a peak of LHA dopamine in both LHA-α-MSH and NAc-α-MSH-infused rats but not in the controls. During food provision, LHA dopamine levels were strongly elevated in LHA-α-MSH infused rats, while delivery of α-MSH into the NAc induced a less intense increase of dopamine in both NAc and LHA. In all rats, LHA dopamine levels correlated inversely with sucrose intake. In conclusion, our study showed that α-MSH stimulates dopamine release in the LHA during both the anticipatory and consummatory phases of feeding, decreases food intake and inhibits sucrose intake. These data suggest that LHA dopamine release can be involved in α-MSH anorexigenic effects. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 03/2015; 56:79-87. DOI:10.1016/j.psyneuen.2015.02.020 · 4.94 Impact Factor
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    • "Indeed, it was previously shown that in both humans and rats, circulating IgG may bind to a-MSH and ACTH [17] [18] and that plasma levels of these autoAbs correlate with some typical behavioral traits in female patients with EDs [19]. Furthermore, a-MSH autoAbs were associated with anxiety and depression in healthy individuals [20] and ACTH autoAbs with antisocial behavior in adolescents [21], suggesting that autoAbs reactive with the melanocortin hormones may physiologically regulate behavioral traits in humans. "
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    ABSTRACT: The biological background of sex-related differences in the development of eating disorders (EDs) is unknown. Recent data showed that gut bacteria Escherichia coli induce autoantibodies against anorexigenic α-melanocyte-stimulating hormone (α-MSH) associated with psychopathology in ED. The aim of this study was to compare the effects of E. coli on feeding and autoantibodies against α-MSH and adrenocorticotropic hormone (ACTH), between female and male rats. Commensal E. coli K12 were given in a culture medium daily to adult Wistar rats by intragastric gavage over a 3-wk period; control rats received culture medium only. Before gavage, E. coli K12 DNA was detected in feces of female but not male rats. E. coli provision was accompanied by an increase in body weight gain in females, but a decrease in body weight gain and food intake in males. Independent of E. coli treatment, plasma levels of anti-α-MSH and ACTH immunoglobulin (Ig)G were higher in female than male rats. Females responded to E. coli by increasing α-MSH IgG levels and affinity, but males by increasing α-MSH IgM levels. Affinity of IgG for ACTH was increased in both E. coli-treated females and males, although with different kinetics. IgG from females stimulated more efficiently α-MSH-induced cyclic adenosine monophosphate production by melanocortin 4 receptor-expressing cells compared with IgG from males. Sex-related response to how E. coli affects feeding and anti-melanocortin hormone antibody production may depend on the presence of these bacteria in the gut before E. coli supplementation. These data suggest that sex-related presence of certain gut bacteria may represent a risk factor for ED development. Copyright © 2015 Elsevier Inc. All rights reserved.
    Nutrition 03/2015; 31(3):498-507. DOI:10.1016/j.nut.2014.11.003 · 2.93 Impact Factor
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    • "In AN patients, plasma α-MSH levels were found not different from those of normal controls (Moriya et al., 2006). Fetissov et al. (2002) demonstrated a significant increase of auto-antibodies to α-MSH in AN and in BN compared with controls. The same research group measured auto-antibodies to α-MSH, adrenocorticotropic hormone, oxytocin (OX) and vasopressin (VP) and showed a significant correlation between the Eating Disorder Inventory-2 score and the levels of auto-antibodies to α-MSH. "
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    ABSTRACT: A large body of literature suggests the occurrence of a dysregulation in both central and peripheral modulators of appetite in patients with anorexia nervosa (AN) and bulimia nervosa (BN), but at the moment, the state or trait-dependent nature of those changes is far from being clear. It has been proposed, although not definitively proved, that peptide alterations, even when secondary to malnutrition and/or to aberrant eating behaviours, might contribute to the genesis and the maintenance of some symptomatic aspects of AN and BN, thus affecting the course and the prognosis of these disorders. This review focuses on the most significant literature studies that explored the physiology of those central and peripheral peptides, which have prominent effects on eating behaviour, body weight and energy homeostasis in patients with AN and BN. The relevance of peptide dysfunctions for the pathophysiology of eating disorders is critically discussed. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.
    European Eating Disorders Review 09/2014; 22(5). DOI:10.1002/erv.2303 · 2.46 Impact Factor
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