Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy

doi:10.1016/0026-0495(93)90216-B

Metabolism

Volume 42, Issue 5, May 1993, Pages 581-584

https://doi.org/10.1016/0026-0495(93)90216-B Get rights and content

Abstract

There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% ± 1.8% (mean ± SEM) of ideal body weight (IBW), and following partial restoration were 84.3% ± 1.4%. Body weights in normal controls were 96.3% ± 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls (P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls. Blood glucose levels following the oral glucose load were essentially the same as those observed in the controls; however, changes in levels of IRI following the glucose load in AN patients before and after treatment were significantly less than those in the controls. These data indicate that basal CCK levels are abnormally elevated in AN patients, and that diminished responses to an oral glucose load are essentially normalized after therapy and partial restoration of body weight. The significance of the elevated basal CCK levels in AN remains to be elucidated.

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Citation Excerpt :
Experiments designed to assess circulating CCK levels in AN have produced mixed results. Increased [114,115] or comparable levels [103,116-119] of plasma fasting CCK have been found in individuals with active AN relative to those with healthy weight. Similarly, total integrated postprandial CCK was found to be either elevated [114,118] or comparable [116,117,119] to levels in controls.
Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted gastrointestinal peptides (i.e., ghrelin, cholecystokinin, glucagon-like peptide 1, and peptide tyrosine tyrosine) that contribute to the control of appetite and discusses how these peptides or the signals arising from their release are disrupted in eating-related disorders across the weight spectrum, namely anorexia nervosa, bulimia nervosa, and obesity, and whether they are normalized following weight restoration or weight loss treatment. Further, the role of gut peptides in the pathogenesis and treatment response in human weight conditions as identified by rodent models are discussed. Lastly, we review the incretin- and hormone-based pharmacotherapies available for the treatment of obesity and eating-related disorders.
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Thinness is a rare condition including very different groups of phenotypes, both physiological and pathological. Those low body mass index situations question the eating habits that can be evaluated through the hormonal profile of appetite regulation. Restriction that can be found in healthy people, obese, anorexia nervosa, or cancer cachexia, increases the orexigenic ghrelin, in an adaptive but ineffective way. Anorexigenic hormones results are more conflictive in literature. Elevation is used to explain anorexia when it is clinically found. Constitutional thinness presents with an overall anorexigenic hormonal profile as this physiological state of underweight is not associated with eating restriction and undernutrition.
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A large body of literature documents the occurrence of alterations in the physiology of both central and peripheral modulators of appetite in acute patients with anorexia nervosa (AN) and bulimia nervosa (BN). Until more recently the role of most of the appetite modulators in the control of eating behavior was conceptualized solely in terms of their influence on homeostatic control of energy balance. However, it is becoming more and more evident that appetite modulators also affect the non-homeostatic cognitive, emotional and rewarding component of food intake as well as non food-related reward, and, recently, AN and BN have been pathophysiologically linked to dysfunctions of reward mechanisms. Therefore, the possibility exists that observed changes in appetite modulators in acute AN and BN may represent not only homeostatic adaptations to malnutrition, but also contribute to the development and/or the maintenance of aberrant non-homeostatic behaviors, such as self-starvation and binge eating. In the present review, the evidences supporting a role of leptin, ghrelin, brain-derived neurotrophic factor and endocannabinoids in the homeostatic and non-homeostatic dysregulations of patients with AN and BN will be presented. The reviewed literature is highly suggestive that changes in the physiology of these modulators may play a pivotal role in the pathophysiology of eating disorders by providing a possible link between motivated behaviors, reward processes, cognitive functions and energy balance.
Eating disorders: Anorexia and bulimia nervosa
2012, Handbook of Clinical Neurology
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The results of studies of CCK in AN are inconsistent. Some studies found elevated basal plasma CCK levels and/or increased postmeal secretion of CCK (Harty et al., 1991; Tamai et al., 1993; Tomasik et al., 2004). Other studies found normal or decreased levels of CCK in AN subjects (Brambilla et al., 1995a; Baranowska et al., 2000).
Eating disorders have morbidity and mortality rates that are among the highest of any mental disorders. This chapter covers diagnoses, epidemiology, course, and outcome of anorexia and bulimia nervosa, presents several factors that are probably important for their etiology, and gives a short overview on intervention. Emphasis is laid on biological contributions to illness onset and maintenance. Genetic predisposition may be an essential risk factor triggered by cultural or social influences and/or personal adversities. The starvation process itself leads to neural circuit dysfunction, probably mediated by altered neurotransmitter metabolism and endocrinological changes. Neuroimaging and neuropsychological studies give insight into disorder-associated alterations of brain structure and function. Starvation-related changes in neuropeptide secretion or function may contribute to maintain typical psychopathology. It is important to understand the neurobiological mechanism underlying these disorders, to develop more effective evidence-based therapeutic strategies.
Effects of an antiandrogenic oral contraceptive on appetite and eating behavior in bulimic women
2007, Psychoneuroendocrinology
Citation Excerpt :
Meal-related peripheral secretion of CCK reflects appetite and eating habits in humans (Hirschberg et al., 1994). In BN, meal-related CCK secretion is reduced (Devlin et al., 1997), whereas in anorexia nervosa, it is increased (Tamai et al., 1993). We have previously demonstrated a suppression of CCK secretion by oral contraceptives (OC) related to an increase in body fat (Karlsson et al., 1992; Hirschberg et al., 1996).
High androgen levels in women with bulimia nervosa may promote bulimic behavior. The aim of the present study was to investigate the effects of an antiandrogenic oral contraceptive (OC) on appetite and eating behavior in women with bulimia nervosa compared to healthy controls. Twenty-one women with bulimia nervosa and 17 healthy controls matched for age and body mass index participated in the study. Basal and meal-related appetite and secretions of the satiety peptide cholecystokinin (CCK) and the appetite-stimulating peptide ghrelin were studied before and after 3 months of treatment with an antiandrogenic OC (30 μg ethinyl estradiol combined with 3 mg drospirenone). Bulimic behavior was evaluated in relation to changes in hormone levels. Before treatment, bulimic women had higher frequency of menstrual disturbances, acne and hirsutism and higher levels of testosterone but lower meal-related CCK secretion than controls. OC treatment reduced meal-related hunger and gastric distention in bulimics. CCK secretion in response to the meal was unchanged in bulimic women but decreased in the controls. Ghrelin secretion was comparable between groups and did not change in response to OC treatment. The treatment improved bulimic behavior in relation to a decline in testosterone levels in the entire group. Our results support the suggestion that androgens play a role in bulimic behavior. Treatment with an antiandrogenic OC may serve as a new strategy for treatment of bulimia nervosa and particularly in those patients with hyperandrogenic symptoms.
Regulation of food intake: A clinical perspective
2005, Endocrinologia y Nutricion
Los avances experimentados en los conocimientos de la fisiología de la regulación de la ingesta alimentaria han permitido identificar un número creciente de moléculas implicadas en los circuitos de apetito-saciedad. Muchas de ellas son sintetizadas en sistemas endocrinos difusos como el tejido adiposo, el tracto gastrointestinal o el sistema nervioso central. Los mecanismos que regulan su secreción y su acción aún no son bien conocidos. No obstante, el descubrimiento de péptidos tales como la leptina, la ghrelina o la colecistocinina, entre otros, nos ha permitido profundizar en el conocimiento de la regulación de la ingesta y sus relaciones con otros sistemas homeostáticos. La emergente neuroendocrinología del apetito y la saciedad nos está suministrando nuevas claves para comprender los mecanismos implicados en la fisiopatología de la obesidad y de los trastornos del comportamiento alimentario. El estudio de las variaciones de las señales de apetito y saciedad que tienen lugar con la pérdida ponderal inducida por la cirugía bariátrica puede conducir al desarrollo de abordajes farmacológicos que permitan reemplazar el tratamiento quirúrgico en los casos de obesidad extrema. Las conexiones recientemente puestas de manifiesto entre la ingesta y el sueño forman parte de otra área de gran interés. Estos conocimientos están abriendo nuevas perspectivas terapéuticas mediante el diseño de fármacos agonistas o antagonistas de los diferentes sistemas funcionales, que en un futuro próximo crearán nuevas expectativas en el control de unas enfermedades de gran prevalencia e impacto sanitario.
The enormous advances in the field of food intake regulation have led to the identification of a growing number of molecules involved in appetite-satiety circuits. Many of these molecules are synthesized in diffuse endocrine systems such as the adipose tissue, the gastrointestinal tract and central nervous system. The exact mechanisms that regulate their synthesis and secretion are not yet well known. Nevertheless, as a consequence of the discovery of peptides such as leptin, ghrelin, and cholecystokinin, among others, greater knowledge is being gained on the pathophysiology of food intake and its relationships with other homeostatic systems. Thus, the neuroendocrinology of food intake is providing us with new keys for understanding the mechanisms involved in the pathophysiology of obesity and eating disorders. Study of the changes in appetite and satiety signals associated with weight loss induced by bariatric surgery may culminate in the design of new therapeutic approaches to substitute surgical treatment in patients with morbid obesity. The recent associations demonstrated between eating and sleeping represent other area of great interest. All this information is opening up new therapeutic perspectives directed at the development of agonist and antagonist drugs, which may prove highly useful in the treatment of highly prevalent diseases with a devastating impact on public health.

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Changes in plasma cholecystokinin concentrations after oral glucose tolerance test in anorexia nervosa before and after therapy

Abstract

Psychoneuroendocrinology

Am J Clin Nutr

Am J Clin Nutr

Brain Res

Brain Res Bull

Body weight and the pituitary response to hypothalamic releasing hormones in patients with anorexia nervosa

J Clin Endocrinol Metab

Hypothalamic endocrine dysfunction in anorexia nervosa

Acta Endocrinol (Copenh)

Hypothalamic-endocrine dysfunction in anorexia nervosa

Role of cholecystokinin and opioid peptides in control of food intake

Physiol Rev

Satiety effects of cholecystokinin and ceruletides in lean and obese men

Ann NY Acad Sci

The satiety effect of cholecystokinin: Recent progress and current problems

Ann NY Acad Sci