Simultaneous decrease of plasma obestatin and ghrelin levels after a high-carbohydrate breakfast in healthy women

Ghrelin is a gut peptide produced mainly by stomach, well known to induce appetite stimulatory actions. Obestatin, a recently identified peptide derived from preproghrelin, was initially described to antagonize stimulatory effect of ghrelin on food intake. The postprandial response of obestatin and its relationship with ghrelin in humans remains unknown. We therefore investigated the postprandial response of obestatin and total ghrelin, acyl and desacyl ghrelin and neuropeptide Y (NPY) to a high-carbohydrate breakfast (1 604 kJ) in eight healthy women (age: 24.2+/-0.82 years; BMI 21.6+/-0.61 kg/m(2)). Blood samples were collected before the meal, and 30, 60, 90, 120 and 150 min after the breakfast consumption. Postprandial plasma obestatin concentrations significantly decreased compared with preprandial levels as well as total ghrelin concentrations and reached the lowest values 90 and 120 min after the meal consumption, respectively (p<0.05). Plasma acyl and desacyl ghrelin concentrations decreased after the breakfast and reached lowest values in 30 and 60 min, respectively (p<0.05). Plasma NPY concentrations were lower than preprandial levels 90 and 150 min after consuming breakfast (p<0.05). In conclusion, we demonstrated in healthy young women that plasma obestatin concentrations decrease similarly to ghrelin after a high-carbohydrate breakfast.     

Total ghrelin plasma level in patients with the restrictive type of anorexia nervosa

Ghrelin is produced mainly in the stomach and is an essential link of the brain-gut axis. Ghrelin stimulates hunger centers in hypothalamus controlling food intake and body mass gain. The aim of the study is to analyze the total ghrelin plasma level in patients suffering from restrictive type of anorexia nervosa (AN-R). According to DSM-IV classification a group of 30 AN-R patients was investigated before and after 3 and 6 months of therapy. Therapy included normocaloric diet and cognitive-behavioral psychotherapy (CBT). The control group consisted of 20 girls without any eating disorders. Before the therapy the total ghrelin plasma level in AN-R patients was significantly higher than in the control group. After 3 and 6 months of treatment the total ghrelin plasma level in AN-R patients was significantly lower than in the control group. In AN-R patients, the total ghrelin plasma level is connected with the pathological feeding behavior.     

Characteristics of suicide attempts in anorexia and bulimia nervosa: a case-control study

Objective

Compared to other eating disorders, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an eating disorders (ED).

Method

Case-control study in a cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.

Results

AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7,95% CI 1.1–13.5), and an increased risk of severity (OR = 3.4,95% CI 1.2–9.6). BN patients did not differ from the control group. Clinical markers of the severity of ED were associated with the seriousness of the attempt.

Conclusion

There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Higher completed suicide rates in AN may be partially explained by AN patients'' higher desire to die and their more severe and lethal attempts.     

Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa

Background  

Over the last five to ten years there has been an increase in psychosomatic complaints (PSC) in Swedish children. The objective of the study was to examine the relation between PSC and sense of coherence (SOC).     

Human atrial natriuretic polypeptide in plasma of patients with anorexia nervosa

To examine the effects of chronic dehydration and starvation on plasma levels of human atrial natriuretic polypeptide (hANP) in human subjects, the basal level and saline-induced rise of plasma hANP in 7 patients with anorexia nervosa were compared with those in age-matched healthy subjects. The unstimulated level of plasma hANP was markedly high in the patients with anorexia nervosa (patients vs. control; 55.4 +/- 9.0 pg/ml vs. 11.4 +/- 6.1 pg/ml, P less than 0.01). However, no significant increase of plasma hANP in the anorectic patients was observed in response to saline-infusion, while a 3-fold increase over the basal level of plasma hANP was noted in the saline-infused normal young subjects. These results show that hANP may be secreted to an inadequate extent, hence the release would be resistant to volume-loading. The pathophysiological meaning of such a high plasma concentrations of hANP in anorexia nervosa is the subject of ongoing studies.     

Effect of nutritional rehabilitation on circulating ghrelin and growth hormone levels in patients with anorexia nervosa

Circulating ghrelin and growth hormone (GH) are up-regulated in anorexia nervosa (AN) as a consequence of prolonged starvation. The current study examines the effect of nutritional rehabilitation with improvement of eating behavior on ghrelin and GH levels in AN patients during the course of inpatient treatment. The subjects included 34 female AN patients and 9 age-matched female controls. Fasting blood samples were collected before, during and after treatment. For data analysis, AN subjects were divided into three subtypes. The first group included seven patients with emergent hospitalization (E-AN), who were accompanied by severe emaciation due to their inability for food intake for more than a month. The other two groups included 14 AN with restricting (AN-R) and 13 AN with binge-eating/purging (AN-BP) patients. There were significant correlations between ghrelin, GH and body mass index (BMI) before treatment in all subjects. However, ghrelin levels were not significantly correlated with BMI and GH although there was a relationship between GH and BMI after treatment. Before treatment, E-AN patients had the highest levels of ghrelin and GH with the lowest glucose levels and liver dysfunction. The AN-BP group had a higher level of ghrelin than the AN-R group. During treatment, comparing with the controls group only the AN-R group showed higher level of ghrelin. Contrarily, the ghrelin levels in the E-AN group, who showed improved glucose levels, and the AN-BP group, who stopped vomiting behavior due to our treatment, decreased ghrelin levels. After treatment, only the AN-BP group showed a higher ghrelin level as compared to the controls. Although GH levels of the three AN groups decreased gradually according to our treatment progress, it still showed the higher value than the control group at the end of the treatment because every AN patients could not reach to more than 80% of their ideal body weight at discharge. These findings suggest that (1) severe emaciation with abnormal fasting hypoglycemia in AN patients may cause very high levels of GH and ghrelin, (2) that GH levels in AN patients may relate to nutritional status and (3) that ghrelin may be influenced by not only nutritional status but also the eating behavior of the patients.     

The role of ghrelin in the regulation of food intake in patients with obesity and anorexia nervosa

Gastrointestinal hormones play an important role in the neuroendocrine regulation of food intake and postprandial satiety. Ghrelin is a 28-amino acid orexigenic peptide produced mainly by the stomach that is involved in both the long-term regulation of body weight and the short-term regulation of postprandial satiety. Impairments in ghrelin secretion may in concert with other factors play an important role in the development of both obesity and anorexia nervosa. Despite an intensive research the critical factors regulating physiological postprandial ghrelin response in healthy individuals and its modification by the presence of obesity and anorexia nervosa are only partially understood. The potential contribution of ghrelin to the differences of diet- vs. surgical-induced weight losses in morbidly obese patients is now also being recognized. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of ghrelin and to discuss its potential in the prevention and/or treatment of obesity and anorexia nervosa.     

Secretory dynamics of ghrelin in adolescent girls with anorexia nervosa and healthy adolescents

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12-18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency.     

Insulin, glucose, and pancreatic polypeptide responses to a test meal in restricting type anorexia nervosa before and after weight restoration

Prolonged malnutrition in individuals with anorexia nervosa (AN) has been associated with alterations in endocrine function that may play a sustaining role in the disorder. We hypothesized that abnormalities in endocrine responses to ingestion of a meal in AN are reversible and depend on weight restoration. We measured meal-induced endocrine responses in AN subjects at three time points during hospitalization: before refeeding (n = 13, mean BMI 16.7 kg/m(2)), after 2 wk of refeeding (mean BMI 18.0 kg/m(2)), and in the weight-restored state (mean BMI 20.3 kg/m(2)). Control subjects (n = 13, BMI 19-24.9 kg/m(2)) were tested once. Tests were 2.5-h sessions in which blood was drawn every 15 min before, during, and after a approximately 650-kcal test breakfast. Relative to controls, peak levels of glucose were depressed and peak levels of insulin in response to ingestion of the test meal were delayed, with response patterns in the third trial most similar to controls. Pancreatic polypeptide (PP) levels were increased in AN relative to controls regardless of weight status. The delay in insulin release and elevated PP levels did not correct with short-term refeeding and may contribute to the high relapse rates and maintenance of AN.     

Serum leptin levels, body fat deposition, and weight in females with anorexia or bulimia nervosa.

The objective of this retrospective study was to investigate the relation between serum leptin level and fat deposition in patients with eating disorders. 40 female inpatients with anorexia (n=24) or bulimia nervosa (n=16) were assessed for leptin level, body mass index (BMI), and percentage body fat by dual-energy X-ray absorbometry (DXA). The results show that percentage body fat is a better predictor for leptin level and clinical findings in eating disordered patients than BMI. We discuss the necessity for DXA measurements in anorectic patients for prognostic and research purposes.     

Serum leptin levels in patients with anorexia nervosa before and after partial refeeding, relationships to serum lipids and biochemical nutritional parameters.

Leptin is a protein hormone produced by adipocytes that provide information about the body fat content. It was previously reported that serum leptin levels were decreased in patients with anorexia nervosa in comparison with healthy control subjects. The aim of our study was to compare serum leptin levels in patients with anorexia nervosa (n=11, initial mean BMI=15.4 kg/m2) before and after partial recovery with control age-matched subjects (n=11, mean BMI= 20.3 kg/m2) and to study the relationships of leptin levels, serum lipids and biochemical nutritional parameters. We found that serum leptin concentrations in patients with anorexia nervosa were significantly reduced in comparison with control subjects (3.61 vs 9.37 ng.ml(-1), p<0.01). Serum cholesterol, triglycerides, total protein and albumin in patients with anorexia nervosa either before or after partial recovery did not differ from the control group. After partial recovery, a significant increase in serum leptin was observed (4.83 vs 3.61 ng.ml(-1), p<0.05), but the values still remained significantly lower than in the control group (p<0.01) Leptin levels correlated positively with the body mass index in the control group and anorexia nervosa group before recovery. The correlation with BMI in the anorexia nervosa group after refeeding was not significant. No significant correlation was found between leptin concentrations and serum lipids, total protein, albumin and prealbumin, respectively. Serum leptin thus represents a sensitive parameter that reflects the nutritional status in patients with anorexia nervosa suitable for long-term follow up during refeeding therapy.     

Expression of obestatin and ghrelin in papillary thyroid carcinoma

Ghrelin and obestatin are two peptide hormones with opposing roles in the control of appetite: orexigenic and anorexigenic, respectively. Loss of appetite is a common, serious complication of many forms of malignancy. The goals of this study were to investigate: (i) whether there are differences in ghrelin and obestatin peptide expression in thyroid tissues from a series of papillary carcinoma cases and normal controls, and (ii) whether there are correlations between tissue ghrelin and obestatin levels in series of papillary carcinoma cases and normal controls. Immunohistochemical analysis showed that in sections of benign human thyroid tissue, anti-ghrelin antibody reacted with intense staining in colloid-filled follicles. In benign thyroid tissues, colloids displayed plentiful dispersion in comparison with papillary microcarcinomas, whereas colloids in malignant thyroid tissues were uncommon. We found markedly lower tissue ghrelin levels in thyroid tissue of patients with papillary carcinomas, compared with normal thyroid tissues (P = 0.001). Immunohistochemical analysis also showed that obestatin in papillary carcinoma stained positively to various degrees. Obestatin tissue levels in papillary carcinomas tended to be slightly higher than those in normal thyroid tissue, but this was not statistically significant (P = 0.29). We also report that thyroid tissue of patients with Hashimoto’s thyroiditis produced ghrelin and obestatin at similar levels as in normal thyroid tissue, even though colloid in Hashimoto’s disease is scarce. We conclude that depressed expression of ghrelin, but not obestatin, is specific to papillary carcinoma, and this difference might constitute a diagnostic tool to differentiate papillary carcinoma from normal thyroid tissue. We currently do not know how these peptides are regulated and what factors are involved in papillary carcinoma, which inhibit the expression of ghrelin but not obestatin. This issue warrants further studies.     

Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects

Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor ( CNR1 ) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa.     

Composition of plasma fatty acids and non-cholesterol sterols in anorexia nervosa

Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. The pattern of plasma fatty acids influences the levels of plasma lipids and lipoproteins. The concentration of plasma lathosterol is a surrogate marker of cholesterol synthesis de novo, concentrations of campesterol and beta-sitosterol reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationship to plasma lipids, lipoproteins, cholesterol precursors and plant sterols. We examined 16 women with anorexia nervosa and 25 healthy ones. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol. Moreover, a decreased content of n-6 polyunsaturated fatty acids was found in all lipid classes. These changes were compensated by an increased content of monounsaturated fatty acids in cholesteryl esters, saturated fatty acids in triglycerides and both monounsaturated and saturated fatty acids in phosphatidylcholine. The most consistent finding in the fatty acid pattern concerned a decreased content of linoleic acid and a raised content of palmitoleic acid in all lipid classes. The changes of plasma lipids and lipoproteins in anorexia nervosa are the result of complex mechanisms including decreased catabolism of triglyceride-rich lipoproteins, normal rate of cholesterol synthesis and increased resorption of exogenous cholesterol.     

Plasma ghrelin levels after two high-carbohydrate meals producing different insulin responses in patients with metabolic syndrome

Ghrelin is an orexigenic peptide produced in the stomach and its plasma levels are decreased acutely in response to ingested nutrients. To further clarify the role of insulin on ghrelin secretion, the present study was designed to investigate whether circulating ghrelin is affected differently by two mixtures of whole-grain breads known to produce low or high insulin responses in obese non-diabetic subjects with metabolic syndrome. After an overnight fast eight obese subjects with the metabolic syndrome (3 men and 5 women; BMI 33.7+/-0.7 kg/m(2); age 55.6+/-1.8 y) received two different meals consisting of whole-grain rye or wheat breads. The comparison group (3 men and 5 women; BMI 22.5+/-0.5 kg/m(2); age 26.0+/-0.9 y) received a wheat bread meal. Blood samples were collected postprandially at time intervals for 2 h. Feelings of hunger and satiety were analyzed using the visual analogue scales. Ghrelin concentrations decreased after bread meals in lean individuals, but not in obese individuals with the metabolic syndrome. Despite the difference in plasma insulin response, there was no difference in plasma ghrelin or feelings of hunger and satiety in patients with metabolic syndrome. After both rye and wheat bread meals, the decrease in ghrelin concentrations seen in normal-weight individuals after wheat bread meal was absent in subjects with metabolic syndrome. Despite the different plasma insulin response in obese patients, ghrelin levels did not change in response to either type of bread meals. In addition, ghrelin levels did not correlate with insulin, glucose, HOMA1-IR and satiety and hunger ratings in either study groups. This indicates that regulation of ghrelin might be altered in obese patients with metabolic syndrome independently of insulin.     

Coenzyme Q10 concentration in plasma and blood cells of juvenile patients hospitalized for anorexia nervosa

The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 °C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients.     

Food restriction,ghrelin, its antagonist and obestatin control expression of ghrelin and its receptor in chicken hypothalamus and ovary

The purpose of the present study was to identify the role of age, nutritional state and some metabolic hormones in control of avian hypothalamic and ovarian ghrelin/ghrelin receptor system. We examined the effect of food restriction, administration of ghrelin 1–18, ghrelin antagonistic analogue (D-Lys-3)-GHRP-6, obestatin and combinations of them on the expression of ghrelin and ghrelin receptor (GHS-R1a) in hypothalamus and ovary of old (23 months of age) and young (7 months of age) chickens. Expression of mRNAs for ghrelin and GHS-R1a in both hypothalamus and largest ovarian follicle was measured by RT-PCR. It was observed that food restriction could promote the expression of ghrelin and GHS-R1a in hypothalamus and ovary of the old chickens, but in the young chickens it reduced expression of ghrelin and did not affect expression of GHS-R1a in the ovary. Administration of ghrelin 1–18 did not affect hypothalamic or ovarian ghrelin mRNA, but significantly increased the expression of GHS-R1a in hypothalamus, but not in ovary. (D-Lys-3)-GHRP-6, significantly stimulated accumulation of ghrelin, but not GHS-R1a mRNA in hypothalamus or ghrelin or GHS-R1a in the ovary. Ghrelin 1–18 and (D-Lys-3)-GHRP-6, when given together, were able either to prevent or to induce effect of these hormones. Obestatin administration increased expression of ghrelin gene in the hypothalamus, but not expression of hypothalamic GHS-R1a, ovarian ghrelin and GHS-R1a. Furthermore, obestatin was able to modify effect of both ghrelin and fasting on hypothalamic and ovarian mRNA for ghrelin GHS-R1a. Our results (1) confirm the existence of ghrelin and its functional receptors GHS-R1a in the chicken hypothalamus and ovary (2) confirm the age-dependent control of ovarian ghrelin by feeding, (3) demonstrate, that nutritional status can influence the expression of both ghrelin and GHS-R1a in hypothalamus and in the ovary (3) demonstrates for the first time, that ghrelin can promote generation of its functional receptor in the hypothalamus, but not in the ovary, (4) show that ghrelin1–18 and (D-Lys-3)-GHRP-6 could not only be antagonists in the action on chicken hypothalamus and ovaries, but also independent regulators and even agonists, and (5) provide first evidence for action of obestatin on hypothalamic ghrelin and on the response of hypothalamic and ovarian ghrelin/GHS-R1a system to food restriction. These data indicate the involvement of both hypothalamic and ovarian ghrelin/GHS-R1 systems in mediating the effects of nutritional status, ghrelin and obestatin on reproductive processes.     

Changes in cytokine production and impaired hematopoiesis in patients with anorexia nervosa: the effect of refeeding

The changes in cytokines and hormones involved in hematopoiesis were studied in the serum of 7 girls with anorexia nervosa, 15-24 yr old, on admission and after 5% and 10% weight gain. Hematopoiesis was studied by in-vitro culturing of circulating granulocyte-macrophage colony forming cells and erythroid burst forming cells. Nutritional status was studied by anthropometric measurements and resting energy expenditure. On admission, granulocyte-macrophage colony forming cells and erythroid burst forming cells were significantly lower than in age-matched controls and increased significantly along weight gain. Blood leptin and erythropoietin levels increased significantly with weight gain. TNF-alpha levels tended to decrease while IL-1beta levels were lower than in the controls on admission (p <0.05) and did not change significantly during weight gain. IL-3, GM-CSF and IL-6 were undetected on admission or along weight gain. The changes in granulocyte-macrophage colony forming cells and erythroid burst forming cells positively correlated with changes in resting energy expenditure and fat free mass. These results may suggest that undernutrition affects hematopoiesis as indicated by the reduction of hematopoietic progenitor cells before treatment and the significant increase with weight gain. The changes in the levels of hormones and cytokines known to be involved in hematopoiesis along refeeding may suggest a role for these factors in anorexia nervosa.