Search

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by irreversible and progressive loss of memory and other cognitive functions. Controversies still exist on the precise mechanisms contributing to neurodegeneration. Obesity and disturbances in metabolic homeostasis are thought to be AD risk factors. Adipokine leptin has receptors in the brain, also in the regions related to AD. Leptin may protect against AD. The aim was to assess leptin and soluble leptin receptor levels in plasma as well as free leptin index (FLI) in correlation with metabolic status of women diagnosed with Alzheimer's disease. Eighteen women with moderate to severe stage of AD, 40 women with AD at early stage, and 42 female controls, matched for age and body mass index, participated in the study. Leptin and soluble leptin receptor levels were measured with RIA and IRMA, respectively. Then, FLI was calculated. In addition, metabolic parameters (lipid profile, glucose and insulin concentrations, HOMA-IR) were estimated. Clinical and anthropometric data were collected. The Mini-Mental State Examination (MMSE) as a cognitive impairment measurement was performed. Correlations with both leptin and FLI, and MMSE, clinical and biochemical parameters were evaluated. Leptin levels and FLI were significantly lower and leptin receptor concentrations were higher in AD subjects when compared with the controls. In AD group leptin, soluble leptin receptor and FLI correlated with selected metabolic parameters but not with MMSE. We conclude that alterations in leptin, leptin receptor, and FLI were the most intensified in advanced AD. However, these results did not correlate with dementia stage measured with MMSE. Therefore, further intensive research is needed to explain the mechanisms involved in this phenomenon., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Available data suggest that estrogens and leptin play a role in the control of the pubertal process. In humans and some mammal species the increase of the activity of gonadotropic axis accompanies the decrease in the rate of growth at puberty. The effect of 17β-estradiol and/or leptin administration on the somatotropic and gonadotropic axes was studied using prepubertal female rats as an animal model., Material and Methods: Prepubertal female rats received estradiol/saline, estradiol/leptin, oil/leptin or oil/saline (vehicles) respectively. The changes of growth rate, and serum 17β-estradiol, leptin, GH, IGF-I and gonadotropins levels as well as LHRH and estrogen receptor (ER) concentrations in the medial basal hypothalamus (MBH) and the pituitary were determined. All hormones concentrations were measured by radioimmunoassay and ER by radioligand methods ., Results: In estradiol and/or leptin treated animals noticeable reduction of rate of growth was found. The decrease of growth in response to estradiol treatment accompanied the increase GH level and the decrease of IGF-I concentration in the circulation. Both hormones operating together activated reproductive axis, what was manifested by a significant increase of LHRH abundant in the hypothalamus as well as elevated LH and FSH levels in the circulation. In these rats a significant decrease of the estrogen receptor concentrations in the pituitary was observed., Conclusion: The role of estradiol and leptin in the control of growth and reproduction seems to overlap only partially. Estradiol plays a significant role in the activation of the reproductive axis, and leptin takes part as a permissive factor in pubertal process.

Objective: CART is involved in the control of food intake and hormonal secretion. We aimed to evaluate the effects of CART on hormonal profile in starved rats., Methods: Study group included 100 male rats. Under conditions of food limitation CART (55-102) was given centrally (icv) or peripherally (iv). Non-starved animals underwent identical procedure. Vehicle (aCSF or saline)-injected rats served and as a controls. 60 minutes after CART or vehicle administration blood was collected to assess pituitary hormones (LH, FSH, PRL, GH, ACTH, TSH), corticosterone and leptin concentrations., Results: Itracerebroventricular CART injection resulted in a significant increase in PRL, GH and corticosterone concentrations in non-starved rats compared with vehicle injected animals. However, in a group of starved animals only leptin levels were decreased in comparison with fasted controls. Peripheral CART administration caused a significant increase in PRL, GH and TSH levels in non-starved rats but no changes in investigated hormone levels were observed in starved animals when compared to saline injected controls., Conclusions: Our results indicate that CART is able to modulate hormonal profile in a non-starved rats. However, the modulatory effect depends on the CART administration method. Interestingly, CART administration, both icv and iv, does not have an impact on pituitary hormones and corticosterone levels in a course of food limitation.

Objectives: To investigate the role of leptin, ghrelin, GH and IGF-1 in energy balance disturbances in Parkinson's disease (PD)., Materials and Methods: Thirty-nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF-1, TSH, T3 and T4, concentrations were evaluated., Results: A lower plasma leptin concentration and a higher serum IGF-1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss., Conclusion: These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.

Objective: Some neuropeptides and monoaminergic neurotransmitters may affect hypothalamic feeding centres, sympathetic activity and thermogenesis. Sibutramine (BTS54524; N-[1-[1(4-chloro phenyl) cyclobutyl]-3methyl N,N-dimethylamine hydrochloride monohydrate) is a new 5-HT serotonin and noradrenaline reuptake inhibitor (SNRI), antiobesity drug. The aim of this study was to evaluate the effects of the sibutramine therapy on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations in obese patients., Methods: Sibutramine, serotonin and noradrenaline reuptake antiobesity drug was administered for 6 months in a dose of 10 mg daily in 60 obese women (BMI 30-40 kg/m2) (mean 34 kg/m2). Plasma NPY, leptin, beta-endorphin and insulin concentrations were measured with RIA methods using commercial kits (Peninsula Lab, Linco, Peninsula Lab, Swierk respectively). The above neuropeptides levels were evaluated before and after the 6 month sibutramine therapy in 60 obese women as well as in 30 obese women on low caloric diet and in 30 of the control group., Results: In 85% obese patients a decrease of body weight was found after 6 month therapy with sibutramine. A decrease in total cholesterol, LDL and triglycerides and an increase in HDL were observed after the sibutramine treatment. We have demonstrated that the sibutramine therapy leads to the decrease of plasma NPY, beta-endorphin, insulin and leptin concentrations in obese patients. After low diet therapy we have observed a decrease in plasma leptin levels, however we did not find significant changes in plasma leptin, NPY, beta-endorphin and insulin concentrations., Conclusions: We suggest that the effects on the disturbed activity of NPY, beta-endorphin, insulin and leptin may be involved in the mechanism of sibutramine action.

Objective: It has been reported that leptin plays an important role in the regulation of food intake and energy expenditure. There are controversial opinions about effects of leptin on the hormonal system. The aim of this study was to estimate the effect of leptin on pituitary hormones release after central and peripheral administration., Methods: Leptin was injected intracerebroventricularly (icv) in a dose of 0.5 microg/5microl aCSF (artificial cerebrospinal fluid) for 5 min in Wistar Kyoto rats. At 60 and 120 min after injections the animals were decapitated. Leptin in a dose of 10 microg in 300 microl of saline was administered intravenously (i.v). At 60 mins the animals were decapitated. Serum rLH, rFSH, rPRL, rTSH, rGH concentrations were measured with RIA methods., Results: After central (icv) injection of leptin we observed an increase of rGH, rTSH and a decrease of rPRL. However, after peripheral (iv) injection of leptin we found a decrease of rGH and rTSH and an increase of rPRL. We did not find any significant changes in LH and FSH after icv and iv injection of leptin., Conclusions: The opposite effects of leptin on pituitary hormones release were observed due to the method of leptin administration. Leptin may play a modulating role in the mechanism of pituitary hormones release.

Objective: It has been reported that the peptides such as orexins, neuropeptide Y (NPY) and leptin may play an important role in the regulation of appetite and energy metabolism. The interaction between leptin, orexins and NPY, as well as between peptides and insulin and cortisol in the different nutritional states have been investigated in animals. However, at present this relationship is poorly understood in humans., Research Methods: Material consisted of 36 obese women and 16 lean women. Plasma orexin A, orexin B, neuropeptide Y (NPY), leptin, insulin concentrations were measured with RIA methods., Results: Plasma orexin A concentrations were significantly lower in obese women as compared with control group. Plasma orexin A was significantly lower in severe obesity (BMI > 40 kg/m2) than that in moderate obesity (BMI < 40 kg/m2). Plasma orexin B concentrations did not change. However, plasma NPY, leptin and insulin levels were markedly higher in obese women, especially in severe obesity., Conclusions: Our results confirmed the thesis that orexin A, NPY, leptin play an important role in the regulation of energy metabolism in humans. In obesity the activity of these peptides is disturbed.

Objectives: The aim of this study was to investigate the influence of NMMA on the mechanism of leptin and NPY action in in vivo and in vitro on pituitary hormone release by female rats in diestrus., Methods: In vivo experiments based on four-day ip injections of: 1) murine recombinant leptin (mrLep); 2) human NPY; 3) saline; 4) NMMA (50 microg) was applied prior to administration of mrLep; 5) NMMA (50 microg) was applied prior to administration of NPY; 6) NMMA (50 microg); 7) NMMA (350 microg) was applied prior to administration of mrLep; 8) NMMA (350 microg). The blood samples for LH and FSH were collected after decapitation of animals on the fifth day of study. In vitro experiments studied the effects of these peptides on LH release from pituitary cell culture., Results: In vivo: Leptin+ NMMA (50 microg) stimulated LH. NPY+ NMMA (50 microg) increased LH. NMMA (350 microg) stimulated FSH release. In vitro: The stimulatory effect of leptin on LH release in vitro was observed after 120 min of incubation, but after 60 mins of incubation the inhibitory effect of leptin on LH release was increased by NMMA. Leptin +NMMA (vs NMMA) decreased LH release with highest statistical significance. NPY 10 nM 60 min after incubation decreased LH release. There was no effect of NMMA on LH release., Conclusion: In vivo results show, that NO probably mediates in leptin action on LH release. Moreover, effects of leptin on LH release from cultured pituitary cells are dependent on time of incubation. NPY decreased LH release in vitro.

Objectives: It has been reported that leptin and neuropeptide Y (NPY) play a role in the control of appetite and in the regulation of hormonal secretion., Methods: Plasma leptin, neuropeptide Y (NPY) and galanin concentrations were estimated in 13 women with bulimia nervosa (BN) 19 women with anorexia nervosa (AN) and in 19 healthy women of the control group (CG)., Results: Plasma leptin concentration in BN was significantly higher than that in AN and it was lower as compared with the control group, despite the same BMI (body mass index) in both the groups. Plasma leptin level in AN was significantly lower as compared with the controls. Plasma galanin concentrations in AN and BN did not differ significantly from the control group. Plasma NPY concentration in AN was lower than that in the control group. However, plasma NPY level in BN was significantly higher as compared with AN and with the control group (CG). The observed increase of NPY in BN was independent of BMI because BMI in bulimia nervosa was normal., Conclusions: The data may suggest that other factors than body weight changes may be involved in the modulation of leptin and NPY release in BN. The pathological behaviour of patients with bulimia nervosa may result from disturbed NPY release which is the strongest orexigenic factor.

Objectives: In many studies it has been reported, that leptin may play an important role not only in the regulation of food intake and body weight but can modify immune response. The aim of our study was to estimate the effects of the administration of exogenous leptin on serum concentration of proinflammatory cytokines (interleukin 6-IL 6 and tumor necrosis factor alpha-TNF alpha) and anti-inflammatory cytokine (interleukin 10 - IL 10) during LPS induced acute inflammation. We also estimated leptin's influence on pituitary, thyroid, adrenal and gonadal hormones in response to lipopolysaccharide (LPS) induced acute inflammation., Methods: Male rats Wistar-Kyoto were divided into four groups, which received respectively: placebo (0.9% NaCl), LPS, leptin and leptin with LPS. The TNF alpha and IL 6 serum concentrations were measured after 2 hours and IL 10 after 4 hours. The pituitary, thyroid, adrenal and gonadal hormones serum concentrations were measured after 2 and 4 hours. Cytokine concentrations were estimated using ELISA tests and hormones concentrations using RIA tests., Results: Leptin did not have an effect on both cytokine responses (proinflammatory and anti-inflammatory) in the time of LPS-induced acute inflammation. Leptin enhanced LPS-induced increasing of corticosterone secretion after 2 hours and decreased LPS-induced inhibition of testosterone secretion after 4 hours., Conclusions: Leptin can modulate hormone response during LPS-induced acute inflammation.