Nedvídková J

Serum leptin levels in patients with hyperlipidemias.

Leptin is a protein hormone produced by adipocytes that reflects the body fat content. The aim of our study was to compare serum leptin levels in randomly selected untreated males and females with hypercholesterolemia and combined hyperlipidemia and in healthy control subjects matched for age and body mass index and to study the relations between leptin and serum lipids and lipoproteins. No statistically significant differences in serum leptin levels were found between the male control group (5.26 +/- 2.81 ng/mL(-1)) and the male group with hypercholesterolemia (8.16 +/- 3.85 ng/mL(-1)) or combined hyperlipidemia (7.51 +/- 4.83 ng/mL(-1)) and between the female control group (13.0 +/- 8.12 ng/mL(-1)) and the female group with hypercholesterolemia (15.36 +/- 8.89 ng/mL(-1)) or combined hyperlipidemia (18.63 +/- 10.15 ng/mL(-1)). Leptin concentration in male group with hypercholesterolemia did not differ significantly from the female control group; in the other male groups, leptin levels were significantly lower than those of the other female groups. Serum leptin levels in all studied groups except for the male group with hypercholesterolemia positively correlated with body mass index. Serum leptin levels correlated negatively with high-density lipoprotein cholesterol in the female group with hypercholesterolemia (r = -0.67, P < 0.01) and the male group with combined hyperlipidemia (r = -0.56, P < 0.01). A positive correlation between serum leptin and high-density lipoprotein cholesterol (r = 0.67, P < 0.01) and between leptin and lipoprotein (a) (r = 0.71, P < 005) was found in female group with combined hyperlipidemia. No other significant relationships between leptin and serum lipids or lipoproteins were found. We conclude that serum leptin levels in patients with hyperlipidemias do not significantly differ from those healthy control subjects matched by age and body mass index.

Relationship of serum leptin levels and selected nutritional parameters in patients with protein-caloric malnutrition

Leptin is a protein hormone produced by adipocytes that reflects the body fat content, i.e., its serum concentration in healthy individuals positively correlates with the body mass index and body fat content. Serum leptin levels are lower in both patients with anorexia nervosa and protein-caloric malnutrition caused by chronic non-malignant illnesses. The aim of the present study was to compare serum leptin levels and selected, routinely used nutritional parameters in women with anorexia nervosa (n = 17), severely malnourished patients with short bowel syndrome (n = 13), and control non-obese healthy women (n = 17) to clarify the relation between selected nutritional parameters and serum leptin levels. We found that serum leptin levels in the anorexia nervosa and short bowel syndrome groups were significantly lower than those in the control group (in ng/mL: 3.63 +/- 1.64 and 2.59 +/- 1.17 versus 12.06 +/- 7.59, respectively). Protein malnutrition expressed by decrease in serum concentrations of total protein, albumin, and prealbumin was more pronounced in the short bowel syndrome group. Triceps skin fold, arm muscle circumference, and body mass index were significantly lower in the patient group than in the control group and did not significantly differ between the short bowel syndrome and anorexia nervosa groups. No significant difference in serum leptin concentration between the short bowel syndrome and anorexia nervosa groups was found. Serum leptin levels correlated positively with body mass index and triceps skin fold in the control and anorexia nervosa groups but not in the short bowel syndrome group. We conclude that serum leptin levels in patients with anorexia nervosa and short bowel syndrome are significantly lower than in healthy individuals and have no statistically significant relation to serum total protein, abumin, and prealbumin.

Interaction between serum leptin levels and hypothalamo-hypophyseal-thyroid axis in patients with anorexia nervosa.

The main objective of the study was to evaluate the endocrinological picture of anorexia. Serum leptin levels are low in untreated anorexia nervosa (AN), but studies of the exact relationship between leptin, body weight and hormones of hypothalamo-hypophyseal-thyroid axis and the impact of refeeding in anorectics are limited. The sample consistent of 15 patients with anorexia nervosa before and 1 mounth after partial weight recovery, and 15 age-matched control subjects. The body mass index (BMI), leptin, plasma neuropeptide Y (NPY), serotonin, thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in serum were evaluated for each subject. The mean serum levels of leptin, T4, and T3 were significantly lower before weight recovery in 15 patients with AN than they were in control subjects. After partial weight recovery, basal T3 levels were unchanged and significantly lower than in controls. Basal T4 was even still more reduced, but we observed significantly elevated ratio of T3/T4 and reduced ratio rT3/T4 of in AN patients after gain recovery, indicating increased conversion of T4 to T3 than to rT3. The levels of serum leptin were low in AN, but after partial weight recovery slightly increased, and correlated with BMI. No differences were observed in serum NPY. Serum levels of IGF-1 and serotonin were lower in AN than in controls before and after partial weight gain IGF-1 was slightly increased after partial weight gain. We did not find correlation between serum levels of leptin and serum T4. The low serum levels of T3 associated with chronic starvation were thought to be the result of impaired peripheral conversion of T4 to T3. However, decreased levels of T3 were still apparent even after a partial weight gain, and the concentration of T4 was even lower. The diminished serum level of TSH in AN, however, appeared to return to the level of controls. On the basis of these results, we assume that low serum levels of thyroid hormones in AN reflect a dysfunction of the HPT axis in AN patients. It is known that in man serum serotonin levels correlate positively with T3 levels. It is possible that the low serum levels of thyroid hormones in AN subjects result in low serum serotonin and its product, melatonin. While IGF-1 reflects the energy intake of the previuos few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis

OBJECTIVE The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. METHODS In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. RESULTS Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41). CONCLUSIONS We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.

Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa

BackgroundThe present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC) and high-protein (HP) breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls.MethodsWe examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7), BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9) and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8). Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits.ResultsFasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups.ConclusionsSignificant increase of obestatin and NPY in AN and BN patients may indicate their important role as the markers of eating disorders. Different reactions of ghrelin and PYY to breakfast consumption among groups suggest that role of these hormones in regulation of energy homeostasis can be adjusted in dependence to acute status of eating disorder.

Changes of Noradrenergic Activity and Lipolysis in the Subcutaneous Abdominal Adipose Tissue of Hypo‐ and Hyperthyroid Patients: An In Vivo Microdialysis Study

Abstract: Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline‐stimulated local lipolysis and to determine local concentrations of lipolysis‐regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four‐fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with β1,2‐adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

Lower serum leptin concentrations in rugby players in comparison with healthy non-sporting subjects – relationships to anthropometric and biochemical parameters

Abstract Leptin is a protein hormone synthesized by adipocytes. Its serum concentrations reflect the total body fat content. Serum leptin concentrations are significantly higher in obese than in lean people and in women than in men. However little information about the influence of physical activity on serum leptin concentrations is available. We have compared the body weight, the body mass index (BMI), the body fat content (measured by caliper as skinfold thickness) and the serum concentrations of leptin, triglycerides, total, high density and low density lipoprotein (LDL) cholesterol in 14 top rugby players and 10 healthy controls. We found that serum leptin, total and LDL cholesterol concentrations were significantly lower in the rugby players group than in the control subjects. The body weight and BMI were significantly higher in the rugby players, while the body fat content was only slightly (non-significantly) higher in the control group. The serum leptin concentrations in both groups positively correlated with the BMI and body fat content and also with LDL concentrations in the control group. The serum leptin concentrations in the rugby players were lower than in the non-sporting subjects despite a similar body fat content in both groups. We would therefore suggest the possibility that regular hard physical training decreases serum leptin concentrations not only by the decrease of total body fat content, but also by a separate mechanism, which is not directly dependent on the changes in the amount of body adipose tissue.

The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

Treatment with the NO-synthase inhibitor, methylene blue, moderates the decrease in serum leptin concentration in streptozotocin-induced diabetes.

It was previously reported that serum leptin concentrations were decreased in rats with streptozotocin-induced diabetes. Also, simultaneous nitric oxide (NO)-synthase inhibitor treatment is known to partially attenuate streptozotocin-induced diabetes development. The aim of our study was to investigate the influence of the NO-synthase inhibitor, methylene blue, on serum leptin concentration and diabetes development. Body weight, blood glucose, glycated hemoglobin and leptin concentration were measured in a control group, diabetic (streptozotocin 70 mg/kg i.p.) group, methylene blue (40 mg/kg in the food) treated group and a diabetic group treated with methylene blue. After six weeks of experiments, blood glucose and glycated hemoglobin increased significantly in the diabetic group vs controls (27.31 vs 5.49 mmol.l(-1), 14.11 vs 6.79%, respectively) and this increase was partially attenuated by simultaneous methylene blue treatment (16.8 vs 27.31 mmol/l, p < 0.05). Body weight and serum leptin fell in diabetic rats vs controls (248.9 vs 342.8 g, 0.57 vs 3.46 ng.ml(-1)). Treatment with methylene blue significantly suppressed the drop of body weight and the increase in blood glucose and glycated hemoglobin concentrations in the diabetic group. The decrease of serum leptin levels was significantly inhibited by methylene blue in the first experiment (1.1 vs 0.57 ng. ml(-1), p < 0.05); the same trend was found in a second experiment but the differences did not reach statistical significance. We conclude that the drop of serum leptin levels in diabetic rats is probably mainly due to streptozotocin-induced insulin deficiency, which is partially attenuated by NO-synthase inhibitor treatment.

The Relationship of Serum Leptin Levels and Parameters of Endurance Training Status in Top Sportsmen

Leptin is a hormone that reflects the body fat content. It was reported that serum leptin levels were decreased in highly endurance-trained sportsmen in comparison with control non-sporting subjects. The aim of our work was to study the relation of serum leptin to blood viscosity and selected spiroergometric parameters of endurance capacity in a group of top rugby players and top race walkers. We have found that both body fat content and serum leptin levels were significantly lower in race walkers than in rugby players (9.68+/-3.65 vs 15.95+/-3.15% and 2.84+/-1.1 vs 3.89+/-1.09 ng x ml(-1) respectively, p<0.05). The positive correlation of serum leptin levels with body fat in both groups. The level of endurance training status was significantly higher in the race walkers group. Serum leptin levels significantly negatively correlated oxygen uptake per body and pulse oxygen per body weight only in rugby players but not in race walkers. Partial correlation test after adjusting for the effect of body fat content showed that leptin itself is not an independent predictor of endurance trainability in this group. Serum leptin levels correlated positively with blood viscosity only in race walkers, but not in the rugby players group. We conclude that serum leptin levels in top sportsmen parallel the changes in body fat content and are not an independent predictor of endurance training of these subjects.