Increased lipolysis of subcutaneous abdominal adipose tissue and altered noradrenergic activity in patients with Cushing's syndrome: an in-vivo microdialysis study.

Cushing's syndrome is associated with typical central redistribution of adipose tissue. The aim of the study was to assess lipolysis and catecholamines and their metabolites in subcutaneous abdominal adipose tissue using an in-vivo microdialysis technique. Nine patients with Cushing's syndrome and nine age-, gender- and body mass index (BMI)-matched control subjects were included in the study. Local glycerol concentrations were significantly increased in subcutaneous adipose tissue of patients with Cushing's syndrome (p<0.001). Plasma noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine were decreased in patients with Cushing's syndrome (p<0.02, p<0.05, and p<0.02, respectively). Adrenaline, noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine concentrations in subcutaneous abdominal adipose were non-significantly higher in patients with Cushing's syndrome. In conclusion, we showed that lipolysis in subcutaneous adipose tissue of patients with Cushing's syndrome is significantly increased as compared to healthy subjects. This finding together with non-significantly increased local catecholamine concentrations in these patients suggests a possible link between increased lipolysis and catecholaminergic activity in subcutaneous adipose tissue.

Plasma levels of total and active ghrelin in acromegaly and growth hormone deficiency.

Ghrelin is an endogenous growth hormone (GH) secretagogue recently isolated from the stomach. Although it possesses a strong GH releasing activity in vitro and in vivo, its physiological significance in endogenous GH secretion remains unclear. The aim of this study was to characterize plasma ghrelin levels in acromegaly and growth hormone deficiency (GHD). We investigated plasma total and active ghrelin in 21 patients with acromegaly, 9 patients with GHD and 24 age-, sex- and BMI-matched controls. In all subjects, we further assessed the concentrations of leptin, soluble leptin receptor, insulin, IGF-I, free IGF-I and IGFBP-1, 2, 3 and 6. Patients with acromegaly and GHD as well as control subjects showed similar levels of total ghrelin (controls 2.004+/-0.18 ng/ml, acromegalics 1.755+/-0.16 ng/ml, p=0.31, GHD patients 1.704+/-0.17 ng/ml, p=0.35) and active ghrelin (controls 0.057+/-0.01 ng/ml, acromegalics 0.047+/-0.01 ng/ml, p=0.29, GHD patients 0.062+/-0.01 ng/ml, p=0.73). In acromegalic patients plasma total ghrelin values correlated negatively with IGF-I (p<0.05), in GHD patients active ghrelin correlated with IGF-I positively (p<0.05). In the control group, total ghrelin correlated positively with IGFBP-2 (p<0.05) and negatively with active ghrelin (p=0.05), BMI (p<0.05), WHR (p<0.05), insulin (p=0.01) and IGF-I (p=0.05). Plasma active ghrelin correlated positively with IGFBP-3 (p=0.005) but negatively with total ghrelin and free IGF-I (p=0.01). In conclusion, all groups of the tested subjects showed similar plasma levels of total and active ghrelin. In acromegaly and growth hormone deficiency plasma ghrelin does not seem to be significantly affected by changes in GH secretion.

Plasma levels of active and total ghrelin in renal failure: a relationship with GH/IGF-I axis.

Ghrelin was originally isolated from the rat stomach and significant amounts were found also in the kidney. Present study was designed to examine changes in ghrelin levels in renal failure and their relationship to the GH/IGF-I axis. Fourty patients with mild-to-severe CRF (19 men, 21 women, aged 62.5 +/- 2.2 years, BMI 27.57 +/- 0.73 kg/m(2)) and 34 healthy control subjects (17 men, 17 women, aged 60 +/- 2.6 years, BMI 27.55 +/- 0.79 kg/m(2)) were included in the study. Total ghrelin levels were significantly increased in patients with chronic renal failure (CRF) (p < 0.0001). Total ghrelin in CRF correlated positively with active ghrelin (p < 0.001), GH (p < 0.05), IGF-I (p < 0.05), free IGF-I (p = 0.0001), IGFBP-3 (p < 0.01), IGFBP-2 and -6 (p < 0.05). Active ghrelin in CRF correlated positively with IGF-I (p < 0.001), free-IGF-I (p < 0.005), IGFBP-2 (p < 0.05) and IGFBP-3 (p < 0.05). However, most of the correlation were markedly reduced and the significance disappeared after adjustment for different creatinine levels. Hemodialysis in patients with end stage renal disease (ESRD) resulted in a significant reduction of plasma total and active ghrelin (p < 0.01 and p < 0.001 respectively). In conclusion we demonstrated elevated plasma levels of total ghrelin in CRF, and a reduction of total and active ghrelin after a single course of hemodialysis in ESRD. The elevation of ghrelin levels could be caused by impaired clearance and/or metabolism of ghrelin in the kidney. We did not prove clearly significant relationship between ghrelin serum levels and parameters of GH/IGF-I axis in study subjects.

Plasma ghrelin levels in patients with end-stage renal disease.

Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.

Ghrelin -- a new endogenous growth hormone secretagogue.

Ghrelin is a new endogenous peptide, discovered in 1999 by Kojima et al., as the result of a search for an endogenous ligand for an orphan receptor of known structure and function. Ghrelin is composed of 28 amino acids and is produced mostly by cells of the stomach, hypothalamus, and hypophysis, but it has also been detected in other tissues. Its discovery is related to the development of a new hypothesis regarding the regulation of growth hormone secretion. It is an antagonist of somatostatin. Ghrelin activates the release of growth hormone from the somatotrophic cells of the hypophysis. It participates in the regulation of energy homeostasis, increases food intake, decreases energy output and exerts a lipogenetic effect. Its metabolic effects do not depend on the GH/IGF-I system, but are mediated by the NPY/Y1 and AGRP receptor system. Ghrelin influences the secretion and motility of the gastrointestinal tract, especially the stomach. The presence of ghrelin and its receptors has also been demonstrated in many other tissues. Its function in these tissues has not yet been studied, thus providing many possibilities for further research.

Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment.

Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia.

Serum ghrelin levels in obese patients: the relationship to serum leptin levels and soluble leptin receptors levels.

Ghrelin is a new endogenous ligand for the growth hormone secretagogue receptor. It activates the release of growth hormone from the pituitary and it also participates in the regulation of energy homeostasis. The aim of the study was to characterize changes in serum ghrelin levels in obese subjects and their relationship to the serum levels of leptin and soluble leptin receptor. Eight obese patients (6 women and 2 men) with body mass index (BMI) 40.3+/-13.4 kg.m(-2) and eight healthy controls (5 women and 3 men) with BMI 22.7+/-1.3 kg.m(-2) were examined. The ghrelin serum levels (165.0+/-58.1 vs. 343.37+/-81.96; p<0.001) and soluble leptin receptor serum levels (7.25+/-3.44 vs. 21.80+/-4.99; p<0.0001) were significantly lower in obese patients. The leptin serum levels (23.45+/-12.90 vs. 6.41+/-2.96; p<0.005) were significantly higher compared to the lean subject group. In both measured groups the levels of serum leptin significantly positively correlated with BMI. We proved a significantly lower serum ghrelin levels in the group of obese patients in comparison with the control group.

[Effect of sideropenic anemia and its therapy on serum levels of leptin]. / Vliv sideropenické anémie a její lécby na sérové hladiny leptinu.

BACKGROUND: Leptin is a protein hormone produced predominantly by adipocytes. Its major role in human body is probably to regulate the food intake through the hypothalamic satiety center. One of the peripheral effects of leptin, which was studied mainly in vitro so far, is its stimulating effect on the haematopoietic stem cells. The information concerning the changes of serum leptin levels in various haematological diseases is very limited. The aim of our study was to explore changes of serum leptin levels in patients with sideropenic anaemia at the time of diagnosis and in the various phases of their treatment. METHODS AND RESULTS: 18 patients with untreated sideropenic anaemia (SA) and 20 healthy age, gender and weight-matched control subjects were included into the study. The blood testing in SA patients was performed before anaemia treatment, at the time of maximal increase of reticulocytes and after haemoglobin levels normalisation. Blood count, serum leptin, erythropoietin (EPO) and transpherine receptor (TfR) levels were estimated in all samples. Basal serum leptin levels in SA patients did not differ significantly from those of control subjects (13.9 +/- 14.6 SD vs 10.4 +/- 8.8 SD ng.ml-1). Treatment anaemia of did not significantly affect the serum leptin levels in SA patients (13.9 +/- 14.6 SD vs 12.9 +/- 12.6 SD vs 12.8 +/- 15.1 SD ng-ml-1). Serum EPO and TfR levels in SA patients were higher before the start of treatment and decreased significantly after the anaemia recovery. In both groups serum leptin levels correlated positively with body mass index. No unambiguous statistically significant relationships between serum leptin levels and blood count parameters or serum EPO and TfR levels were found in any of the groups studied. CONCLUSION: Neither the changes of red blood cell count during the sideropenic anemia treatment nor the increased erythropoiesis affect significantly serum leptin levels.

[The effect of partial refeeding on serum levels of leptin and resting energy expenditure in female patients with anorexia nervosa]. / Vliv cástecné realimentace na sérové koncentrace leptinu a klidový energetický výdej u pacientek s mentální anorexií.

BACKGROUND: Serum leptin levels and resting energy expenditure are significantly decreased in patients with anorexia nervosa compared to healthy subjects. Partial realimentation of patients with anorexia nervosa increases both these parameters. However, there so far are no data concerning the relationship of serum leptin levels and resting energy expenditure in patients with anorexia nervosa. The aim of our study was to follow the relationship of serum leptin levels and resting energy expenditure in patients with anorexia nervosa before and after refeeding. METHODS AND RESULTS: It was found that serum leptin levels in patients with anorexia nervosa both before and after partial realimentation were significantly lower compared to healthy subjects (0.86 +/- 0.9 ng.ml-1 and 1.77 +/- 1.9 ng.ml-1 vs 6.85 +/- 3.0 ng.ml-1, p < 0.05). The total resting energy expenditure in patients with anorexia nervosa both before and after realimentation were significantly lower than in the control group (4973 +/- 979 and 5263 +/- 899 vs 6401 +/- 827 kJ/day, p < 0.05). When expressed per body weight the resting energy expenditure in patients with anorexia nervosa was significantly higher in comparison with the control group (122.3 +/- 20.6 and 121.5 +/- 14.2 vs 104.2 +/- 14.6 kJ/day, p < 0.05). The differences in resting energy expenditure in patients with anorexia nervosa before and after refeeding did not reach statistical significance. The body mass and the body fat content increased significantly after realimentation index (14.5 +/- 1.4 vs 15.6 +/- 1.5 kg.(m2)-1 and 14.9 +/- 3.4 vs 16.6 +/- 3.7, p < 0.05) but remained still below of those of control group (BMI 22.3 +/- 2.7, body fat content 26.9 +/- 4.2). CONCLUSIONS: Our study confirmed the reduced serum leptin levels and the total resting energy expenditure in patients with anorexia nervosa compared to healthy age-matched subjects. No statistically significant relationships were found between serum leptin levels and resting energy expenditure either in healthy subjects or in patients with anorexia nervosa before or after partial realimentation respectively.

[The changes in serum ghrelin levels and their relationship to IGF-I, its binding proteins and leptin in women patients with anorexia nervosa]. / Zmeny sérových koncentrací ghrelinu a jejich vztah k IGF-I, jeho vazebným proteinum a leptinu u pacientek s mentální anorexií.

Ghrelin is recently discovered peptide hormone involved in the regulation of growth hormone secretion as well as in the regulation of food intake and energetic homeostasis. The study was aimed to describe the changes in ghrelin serum levels in patients with anorexia nervosa and its relationship to some other studied parameters. Sixteen women patients with anorexia nervosa and thirteen healthy women of comparable age were examined clinically and blood samples were taken for estimation of serum levels of ghrelin, leptin, soluble leptin receptor, IGF-I, IGFBP-1 and IGFBP-3. Ghrelin serum levels were significantly increased in the group of patients with anorexia nervosa (p < 0,05). In contrary, serum leptin levels were decreased in the group of patients with anorexia nervosa (p < 0,01). Serum ghrelin levels did not correlate with any other of studied parameters with exception of BMI. We can conclude that serum ghrelin levels are increased in patients with anorexia nervosa and their increase fails to significantly stimulate food intake in this group of patients.

[Effect of hypercortisolism on development of atherosclerotic changes in blood vessels]. / Vliv hyperkortizolismu na vznik a vývoj aterosklerotických cévních zmen.

UNLABELLED: Hypercortisolism is associated with a high risk of sickness rate and death rate particularly in view of facilitated arteriosclerotic processes. It is most frequently induced by drug therapy, but endogenous hypercortisolism (Cushing's syndrome) may serve as a suitable model of the effect of hypercortisolism on vascular wall. Our cohort included the following groups of patients and control individuals: 1. a group of patients with florid so far untreated Cushing's syndrome--14 patients, 2. a control group to these patients--16 individuals, 3. a group recently operated on and healed-up patients with Cushing's syndrome--8 patients, 4. a group of previous of previous cured-up patients with Cushing's syndrome--27 subjects, 5. a control group to those patients of group 4--17 persons. The following differences were found between the respective groups: 1. the ultrasonographic examination of carotid arteries demonstrated sclerotic plates or carotid stenosis in 21.3% of patients with florid Cushing's syndrome and 41.4% in patients with corticolism having been cured-up against 11.7% in the relevant control group; 2. the examination of skin microcirculation by the laser-doppler method revealed a lower velocity of perfusion increase during examination of postocclusion hyperemia in patients with florid Cushing's syndrome and hypercortisolism having been cured-up against a control group (CUSH., P < 0.04; previous cured-up, P < 0.02) as well as thermally-induced hyperemia (CUSH., P < 0.03; formerly cured-up, P < 0.04); 3. the laboratory examination of patients with florid Cushing's syndrome revealed higher values of LDL-cholesterol (P < 0.05) and total cholesterol (P < 0.001), malonyldialdehyde as an indicator of increased formation of oxygen radicals (P < 0.05) and oromucoid, the protein of acute phase, signaling a chronic inflammation (P < 0.05); 4. in patients who previously suffered from hypercortisolism increased levels of fibrinogen (P < 0.03) and the cytoadhesive molecule ICAM-1 (P < 0.05) were accompanied by decreased levels of the growth factor of vascular endothelia (VEGF) (P < 0.05) against patients with florid Cushing's syndrome. CONCLUSION: The findings of the examinations performed indicate that increased incidence of arteriosclerotic processes is present in patients with the florid Cushing's syndrome as well as in those who have suffered from Cushing's syndrome before.

[Relation of serum leptin levels and regulation of resting energy expenditure]. / Vztah sérových koncentrací leptinu k regulaci klidového energetického výdeje.

Leptin is a protein hormone produced by adipocytes. Its serum concentrations in the most of cases positively correlate with total body fat content and body mass index (BMI). Leptin plays a role in the food intake regulation. It also increases resting energy expenditure in hypoleptinaemic ob/ob mice. Its relationship to resting energy expenditure in human is less clear. The aim of our study was to follow the serum leptin levels in healthy females (n = 12) and males (n = 14) and their relationship to resting energy expenditure, body fat content, other antropometric and nutritional biochemical parameters. It was found that serum leptin levels were significantly higher in females comparing to males (6.8 +/- 3 ng.ml-1 vs. 2.6 +/- 1 ng.ml-1, p < 0.05). The serum leptin levels correlated positively with body fat content and body mass index in both groups. In females the positive correlation between body weight and serum leptin levels was found. No statistically significant relationship between serum leptin levels and resting energy expenditure, serum total protein, albumin or prealbumin concentration was found in any of studied groups. The results of our study do not testify to direct relationship between serum leptin levels and resting energy expenditure in young healthy individuals.

Ghrelin as an acute-phase reactant during postoperative stress response.

Ghrelin is a growth hormone-releasing peptide, discovered in 1999 by Kojima et al. Its potential role in inflammation and stress response is not yet clear. The purpose of this study was to characterize perioperative levels of circulating ghrelin in relation to different surgical procedures. The authors compared plasma ghrelin changes with cortisol, cytokines, and acute-phase proteins. The prospective study was performed on 22 patients with resection for colon cancer (group 1). Group 2, functioning as a comparative group, consisted of 22 patients with elective laparotomic cholecystectomy. Plasma concentrations of ghrelin, cortisol, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, IL-6, IL-8, soluble IL-2 receptor, C reactive protein, and alpha1-antitrypsin were estimated repeatedly during a 72-hour postoperative period. Data revealed significant elevation of plasma ghrelin 24 hours after resection of coli (median 508.0 ng/l, interquartile range 398.2-633.7 ng/l) in relation to both preoperative levels (317.6 ng/l, 253.4-355.1 ng/l, p<0.01) and group 2 maximal postoperative levels (386.2 ng/l, 324-432 ng/l, p<0.05). Ghrelin levels returned to initial status 36-48 hours after surgery with subsequent decline to subnormal levels. The regression coefficient was the highest for ghrelin and TNF-alpha 24 hours after laparotomy (r=0.64, p<0.05) and for ghrelin and IL-6 24 hours after surgery (r=0.56, p<0.05). Maximal postoperative levels of all tested parameters except for cortisol and IL-1beta differed significantly between both patient groups at p<0.05. After large abdominal surgery, ghrelin shows itself as an acute-phase reactant. The significant correlation between ghrelin and inflammatory cytokines supposes their regulatory role in this period. Our comparison of more- and less-invasive surgical procedures with similar nutritional restrictions argues for a dominant role of inflammatory factors in postoperative ghrelin elevation.

Endocrine and metabolic activities of a recently isolated peptide hormone ghrelin, an endogenous ligand of the growth hormone secretagogue receptor.

Ghrelin is a member of the group of growth hormone secretagogues (GHSs). It is a peptide hormone, recently isolated from stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Ghrelin is mostly produced by the stomach, although its production has been proved in various tissues. It is a potent releaser of growth hormone (GH) from anterior pituitary cells, but it also stimulates the release of other hypophyseal hormones. Ghrelin stimulates food intake and induces metabolic changes leading to an increase in body weight and body fat mass. This effect seems to be independent of GH action and needs an intact NPY/AGRP (neuropeptide Y/agouti-related protein) system. Plasma ghrelin levels are decreased in obesity, elevated in cachexia and show a diurnal rhythm. Its preprandial elevation suggests, that it might be a signal for meal initiation. Ghrelin further stimulates the release of gastric acid and gastric motility and affects pancreatic functions. It has vasodilatatory, cardioprotective and antiproliferative effects. This article is focused on ghrelin's endocrine and metabolic functions.

Plasma ghrelin levels and malnutrition: a comparison of two etiologies.

Ghrelin is a peptide hormone that is involved in regulating growth hormone secretion as well as food intake and energy homeostasis. The aim of this study was to compare changes in plasma ghrelin levels in patients with malnutrition due to anorexia nervosa (AN) or short bowel syndrome (SBS). Blood samples for laboratory analyses were taken from 16 AN patients (plus 13 comparable healthy controls) and 27 SBS patients (plus 13 comparable healthy controls) after an overnight fast. In comparison with their respective control groups, plasma ghrelin levels were increased in the AN patients (p < 0.05) and significantly decreased in the patients with SBS (p < 0.01). These results suggest that quantitative ghrelin secretion in the gut wall is important in determining ghrelin concentrations in the systemic circulation.