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

Abstract

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 ␣-melanocyte-stimulating hormone (␣-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and͞or BN patients studied had in their plasma Abs that bind to melanotropes and͞or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to ␣-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with ␣-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with ␣-MSH or adrenocorticotropic hormone. Additionally, 3 AN͞BN sera bound to luteinizing hormonereleasing 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 AN͞BN staining. These data provide evidence that a significant subpopulation of AN͞BN patients have autoantibodies that bind to ␣-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 circuitry͞LHRH system and͞or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and͞or could be involved in the pathophysiology or clinical presentation of AN͞BN, and to what extent increased stress is an important factor for production of these autoantibodies.A norexia nervosa (AN) and bulimia nervosa (BN) are two officially recognized eating disorders that affect Ϸ3% of women during their lifetime (1). Both illnesses usually make their debut at young age and are characterized by hyperactivity and exaggerated concern about body shape and weight, and they often occur in the same patients (2). AN is manifested by an aversion to food, often resulting in life-threatening weight loss and amenorrhea, whereas BN includes large uncontrolled eating episodes followed by compensatory vomiting without significant change in body weight. Even if the cause(s) of AN and BN is still unclear, a body of data exists suggesting a primary neurobiological origin (3), and neuropeptides also have been implicated in these disorders (4). These assumptions are paralleled by growing evidence for a role of hypothalamic peptidergic neurons in conditions associated with energy deprivation or energy excess, providing a concept for central mechanisms controlling food intake and body weight (5-7). In a search of possible mechanisms implicating hypothalamic peptidergic neurons in the etiology and pathogenesis of AN͞BN, we hypothesized that hypothalamic systems responsible for the regulation of food intake could be targeted by autoantibodies...

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

“…Human sera were applied to sections of rat brains (Fetissov et al, 2002). Approximately 74% of human sera bound to rat pituitary melanotropes and corticotropes, and approximately 20% selectively bound to α-MSH projections.…”

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

“…Recently, auto-antibodies against the MC system were detected in plasma of AN patients, which could possibly interfere with MC signaling and contribute to pathophysiology (Fetissov et al, 2002). Polymorphisms in the MC4-R gene (Val103Ile, Ile251Leu) and AgRP gene (Ala67Thr) have also been found in AN patients.…”

Body weight is regulated by the brain: a link between feeding and emotion

“…Nevertheless, evidence suggests that several CNS systems regulating energy balance may be dysregulated in patients with mental illnesses, for example, eating disorders, and drug addiction. [8][9][10][11][12][13][14] In the current review, we will illustrate the neuroanatomic and molecular genetic aspects of the melanocortin and neuropeptide Y (NPY) systems residing in the CNS downstream of leptin and ghrelin, to discuss the neural bases of feeding, metabolism, and emotion. Additionally, we point the reader to recent reviews for other critical CNS systems regulating food intake and body weight, including those by Barsh and Schwartz, 15 Elmquist et al, 16 Friedman and Halaas, 17 Friedman, 1 Grill and Kaplan, 18 O'Rahilly et al, 19 Saper et al, 20 Sawchenko, 21 Schwartz et al, 22 Spiegelman and Flier, 23 van den Pol, 24 Woods et al, 25 Zigman and Elmquist.…”

“…It is also interesting to speculate based on the observation that auto-antibodies are raised against a-MSH and adrenocorticotropic hormone in patients with anorexia and bulimia nervosa. 9 Taken together, it is conceivable that 5-HT action on Arc melanocortinergic neurons may contribute to the pathophysiology of morbid ingestive behavior. The Arc provides reciprocal innervation to the DR nucleus, 194,195 supporting an interaction between these two brain sites.…”