Pathophysiology Of Anorexia Research Articles

Changes of BMI, steroid metabolome and psychopathology in patients with anorexia nervosa during hospitalization

Anorexia nervosa (AN) is associated with various alterations including the dysfunction of the HPA axis and consequently the hypercortisolemia and deficit in sex hormones but the comprehensive evaluation of changes in circulating steroids during the hospitalization of AN patients is lacking. We investigated the effect of realimentation of women with AN during hospitalization on 45 circulating steroids, the relationships between BMI, its change during hospitalization and physical activity, on one side and initial levels and their changes for two adipokines, circulating steroids, anorexia-specific (hunger, appetite and satiety), and anorexia non-specific symptoms (anxiety, depression fatigue, sleep, and body pain) on the other side. We included 33 women with anorexia who were hospitalized for 38(35, 44) days (median with quartiles).The increase of BMI from the initial value 15.2 (13.2, 16.6) kg/m2 was 1.69 (1.37, 2.66) kg/m2. The patients with more severe anorexia showed higher activity in 7β-, and 16α-hydroxylation of androgen precursors, which declined during hospitalization. Otherwise, the 7α-hydroxylation activity is higher in AN patients with less severe malnutrition and the ratio of 5-androstene-3β,7α,17β-triol to 5-androstene-3β,7β,17β-triol increased during the realimentation.Our data allow to speculate that the intensive 7β-, and 16α- and possibly also the 7α-hydroxylation of C19 Δ5 steroids participate in the pathophysiology of anorexia by additional catabolism of substrates available for synthesis of active androgens and estrogens. However, the question remains whether the synthetic analogues of 7α/β- and 16α-hydroxy-steroids prevent the catabolism of the sex steroid precursors, or further activate the “energy wasting” mitochondrial thermogenic metabolism.

Pathophysiology of anorexia in the cancer cachexia syndrome.

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Oxytocin Secretion Is Associated with Severity of Disordered Eating Psychopathology and Insular Cortex Hypoactivation in Anorexia Nervosa

Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. This was a cross-sectional study. The study was conducted at a clinical research center. Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula. Oxytocin may be involved in the pathophysiology of anorexia.

Elevation of homocysteine levels is only partially reversed after therapy in females with eating disorders

Recent studies have shown elevated homocysteine levels in patients with eating disorders. In a prospective, longitudinal study, we investigated differences of homocysteine plasma levels in patients with anorexia nervosa (N = 12) and bulimia nervosa (N = 17) compared to healthy controls (N = 20) and alteration of homocysteine levels in patients during specific in-patient treatment. We found significantly elevated homocysteine levels in both patient groups (anorexia nervosa and bulimia nervosa) and a non-significant decrease of homocysteine during the 12-week treatment period. Furthermore, we found a significant association between low homocysteine levels and cognitive deficits, pointing toward a beneficial effect of elevated homocysteine levels on cognition in this patient group. We suppose that during effective treatment with significant increase of the body mass index, the observed hyperhomocysteinemia in patients with eating disorders is partially reversible. These findings add further evidence to the hypothesis that homocysteine might be involved in the pathophysiology of anorexia and bulimia nervosa.

Cachexia and aging: an update based on the Fourth International Cachexia Meeting.

This manuscript highlights the new developments in the pathophysiology of anorexia, cachexia and sarcopenia, based on presentations given at the Fourth International Cachexia Meeting. It stresses the importance of these conditions in older persons.

Anorexie secondaire à des pathologies

Anorexia is frequent in course of malignancies and inflammatory diseases. Cytokines, produced in excess, have a major role in pathophysiology of anorexia. Early oral or enteral nutrition could prevent malnutrition and its complications (infectious,…).

Cannabinoids in the treatment of the cachexia-anorexia syndrome in palliative care patients

Loss of appetite and cachexia are frequent symptoms in palliative care patients. However, therapeutic regimens often prove ineffective, and the quality of life of many patients is significantly impaired by these symptoms. Causes and pathophysiology of anorexia and cachexia are complex and must be identified and treated. Symptomatic pharmacological therapy aims at metabolic, neuroendocrinological and catabolic changes. Prokinetic drugs, corticosteroids and gestagenes are used for symptomatic therapy. Recently, the use of cannabinoids for treatment of loss of appetite and cachexia has become the focus of interest. In cancer patients, cannabinoids proved more effective than placebo but less than gestagenes. Compared to placebo, higher efficacy of cannabinoids could be demonstrated in patients with AIDS as well as in patients with Morbus Alzheimer. However, side effects, such as dizziness, tiredness and daze led to discontinuation of the cannabinoid therapy in some patients.

Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa.

The aim of this study was to examine whether anorexia and bulimia nervosa are accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4.21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleaves peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive peptides, such as arginine vasopressin, luteinizing hormone-releasing hormone, thyrotropin releasing hormone,alpha-melanocyte secreting hormone, substance P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Serum PEP activity was measured in the serum of 18 normal women, 21 anorexia nervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum PEP activity was significantly lower in patients with bulimia nervosa and anorexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between serum PEP activity and the HDRS and BITE. In anorectic patients, but not in normal or bulimic patients, there was a significant correlation between serum PEP and body mass index. In bulimic patients, but not in normal or anorectic patients, there was a significant correlation between serum PEP and duration of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are substrates of PEP, could be an integral component of eating disorders.

Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa.

The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders.

Elevated plasma cholecystokinin at high altitude: metabolic implications for the anorexia of acute mountain sickness.

The aims of the present study were to measure the satiety neuropeptide cholecystokinin (CCK) in humans at terrestrial high altitude to investigate its possible role in the pathophysiology of anorexia, cachexia, and acute mountain sickness (AMS). Nineteen male mountaineers aged 38 +/- 12 years participated in a 20 +/- 5 day trek to Mt. Kanchenjunga basecamp (BC) located at 5,100 m, where they remained for 7 +/- 5 days. Subjects were examined at rest and during a maximal exercise test at sea-level before/after the expedition (SL1/SL2) and during the BC sojourn. There was a mild increase in Lake Louise AMS score from 1.1 +/- 1.2 points at SL1 to 2.3 +/- 2.3 points by the end of the first day at BC (P < 0.05). A marked increase in resting plasma CCK was observed on the morning of the second day at BC relative to sea-level control values (62.9 +/- 42.2 pmol/L(-1) vs. SL1: 4.3 +/- 8.3 pmol/L(-1), P < 0.05 vs. SL2: 26.5 +/- 25.2 pmol/L(-1), P < 0.05). Maximal exercise increased CCK by 78.5 +/- 24.8 pmol/L(-1), (P < 0.05 vs. resting value) during the SL1 test and increased the plasma concentration of non-esterified fatty acids and glycerol at BC (P < 0.05 vs. SL1/SL2). The CCK response was not different in five subjects who presented with anorexia on Day 2 compared with those with a normal appetite. While there was no relationship between the increase in CCK and AMS score at BC, a more pronounced increase in resting CCK was observed in subjects with AMS (> or =3 points at the end of Day 1 at BC) compared with those without (+98.9 +/- 1.4 pmol/L(-1) vs. +67.6 +/- 37.2 pmol/L(-1), P < 0.05). Caloric intake remained remarkably low during the stay at BC (8.9 +/- 1.4 MJ.d(-1)) despite a progressive decrease in total body mass (-4.5 +/- 2.1 kg after 31 +/- 13 h at BC, P < 0.05 vs. SL1/SL2), which appeared to be due to a selective loss of torso adipose tissue. These findings suggest that the satiogenic effects of CCK may have contributed to the observed caloric deficit and subsequent cachexia at high altitude despite adequate availability of palatable foods. The metabolic implications of elevated CCK in AMS remain to be elucidated.