Significant Increase In Leptin Levels Research Articles

Green Tea Extract has a Protective Effect on Leptin and Lipid Profile Levels Due to the Induction of Depot Medroxyprogesterone Acetate.

Depot medroxyprogesterone acetate (DMPA) is a progesterone derivative synthesized in the laboratory. This substance has the ability to suppress ovulation, induce endometrial shrinkage, and even affect the hypothalamic-pituitary-gonadal axis in the reproductive system. The purpose of this study was to investigate the effects of administration of green tea extract on reducing visceral fat, increasing leptin levels, and improving the lipid profile in female rats injected with depot medroxyprogesterone acetate (DMPA). This study was to look into the effects of green tea extract administration on visceral fat reduction, leptin levels, and lipid profile improvement as a result of DMPA administration. Analysis of HDL and LDL levels was performed by spectrophotometry. DMPA induced a significant increase in leptin levels compared with the control group (p 0.05). All doses of green tea extract can reduce this increase, with the highest doses reaching levels comparable to the control group (p > 0.05). DMPA significantly increased LDL levels compared to the control group (p < 0.05), and the highest green tea extract dose restored levels similar to the control group. DMPA triggered a decrease in HDL level that was significantly different from the control group (p < 0.05). The first dose of green tea extract can achieve HDL levels comparable to the control group (p > 0.05). It was concluded that green tea extract can protect the metabolic status through decreased leptin and an improvement of the lipid profile induced by DMPA.

Effects of angiotensin receptor-neprilysin inhibitors (ARNIs) on the glucose and fat metabolism biomarkers leptin and fructosamin

Abstract Background Heart Failure with reduced ejection fraction (HFrEF) has a life time risk about 20% among adults aged 40 years or older and a 5-year mortality rate about 60% [1,2]. However novel therapies have shown to improve this outcome. One novel agent are angiotensin receptor-neprilysin inhibitors (ARNIs) that increase the BNP levels via inhibiting neprilsyin [3]. This has beneficial effects on heart failure by reducing preload, inflammation and fibrosis. Neprilysin also interacts with leptin and is known to correlate with the incidence and progression of heart failure if chronically elevated [4]. Furthermore beneficial affects of ARNI therapy on glucose metabolism were reported in a post-hoc analysis of the PARADIGM-HF trial [5]. In this study we aim to investigate the effect of ARNI therapy on the fat metabolism markers leptin and on the glucose metabolism marker fructosamin. Methods In total, we included 74 patients with HFrEF with ischemic (N=37) and non-ischemic (n=37) origin in the present study. The mean NYHA class was II–III, the mean BMI 28 (SD 6.3). Patients had well established heart failure therapy before starting ARNI therapy with sacubitril/valsartan. 88% of patients were on ACE-inhibitors, 86% on beta blockers and 68% on mineralocorticoid receptor antagonists. Serum samples were obtained and analyzed for leptin, fructosamin and pBNP before and 3–6 month after ARNI therapy. The clinical parameters LVEF and NYHA class were assessed before and 3–6 month after ARNI therapy. Results Baseline leptin level was 15.0 (SD 17.2), baseline fructosamin level was 370.1 (SD 167.7) and baseline pBNP level was 1494.9 (SD 1281.4). Under therapy a significant improvement of ejection fraction from 29,8% to 37,5% (7,7 SD 8,5 P≤0.001), an improvement of NYHA stadium from 2.46 (SD 0.62) to 1.96 (SD 0.63, p=0.005) and a significant decrease of pBNP (562.1 SD 1256.4, p=0.018) was found. Along with that, a significant increase in leptin levels (3.6 SD 8.85, p=0.012) and a significant increase in fructosamine levels (93.5 SD 160.6, p=0.013) was shown. Conclusion Under therapy with ARNI we showed a sufficient therapy response with improvement of ejection fraction and decrease of pBNP in line with literature. Surprisingly metabolism biomarkers did significantly worsen under the first three to six month after new ARNI therapy. To distinguish between a side effect of ARNI therapy or consequence of heart failure itself further investigations are needed. Funding Acknowledgement Type of funding sources: None.

Prognostic Observational Analysis of BMI, Leptin, and Adiponectin in Children With Acute Lymphocytic Leukemia Undergoing Remission-Induction Chemotherapy.

BackgroundThe survival rate of children and adolescents with acute lymphoblastic leukemia (ALL) has progressively improved. However, ALL survivors often have adverse effects after treatment, such as an increased risk of obesity. Obesity has been associated with reduced survival.ObjectiveWe investigated the relationship between obesity, adipocytokine levels, and ALL short-term outcomes.MethodsWeight and height were measured, and body mass index (BMI) was calculated at patient diagnosis and discharge. Leptin and Adiponectin levels and Minimal Residual Disease (MRD) were measured before therapy, at days 19 of remission-induction therapy, and at the end of remission-induction therapy (days 46). The relationship between BMI, adipocytokine levels, and MRD was then determined.ResultsCompared to the normal BMI group, children with an abnormal increase in BMI had an increase in MRD at day 19 and 46 (P = 0.04 and P = 0.008), and showed a positive correlation (P = 0.014). In addition, we found a positive correlation between weight, hip circumference at diagnosis and at day 19, and MRD at day 46. Both BMI and fat concentric distribution affected the outcome of ALL children. A higher BMI was also associated with a significant increase in Leptin levels at diagnosis. Leptin resistance should be considered in ALL children with high BMI.ConclusionBMI affects the outcome of ALL patients. Early interventions such as regular weight, height monitoring, and dietary assessments should be preferably initiated during remission-induction chemotherapy.

Predicting the risk of left ventricular diastolic dysfunction in obesity

Obesity may develop heart failure with preserved ejection fraction, which is based on left ventricular diastolic dysfunction (LV DD). Currently, the search for effective predictors of LV DD is extremely relevant.Aim. To assess the prognostic value of key and additional metabolic risk factors (RFs), neurohumoral and profibrotic factors in the development of LV DD in obese patients.Material and methods. The study included 149 men with general obesity. The mean age was 49,7±7,9 years. The inclusion criteria was the presence of class I-III general obesity. The average body mass index was 32,9±3,6 kg/m2. The exclusion criteria were hypertension, coronary atherosclerosis, type 2 diabetes, as well as LV DD according to transthoracic echocardiography. Depending on the presence of epicardial adiposity, patients were divided into two groups: group 1 — epicardial adipose tissue (EAT) thickness ≥7 mm (n=70), group 2 — EAT &lt;7 mm (n=31). In all patients, the following laboratory parameters were determined in blood serum using enzyme immunoassay: type I and III collagen, Procollagen I C-Terminal Propeptide (PICP), matrix metalloproteinase-3 (MMP-3), transforming growth factor β1, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, C-reactive protein (CRP), adiponectin, soluble leptin receptor, leptin, lipid parameters and free fatty acids (FFA). After 4,7±0,3 years, echocardiography was repeated in order to assess LV diastolic function.Results. Comparative analysis of metabolic risk factors revealed a significant increase in the level of total cholesterol (p=0,001), low-density lipoprotein cholesterol (LDL-C) (p&lt;0,0001), triglycerides (TGs) (p&lt;0,0001). These groups had no differences in such parameters as high-density lipoprotein cholesterol (p=0,09) and glucose (p=0,12). An increase in the level of such pro-inflammatory cytokines as TNF-α (p&lt;0,0001), CRP (p&lt;0,0001), IL-6 (p&lt;0,0001) in group 1 was revealed, while differences in IL-10 (p=0,34) levels were not significant. In group 1, there was a significant increase in leptin levels (p&lt;0,0001), a decrease in levels of adiponectin (p&lt;0,0001) and leptin receptor (p=0,001). In group 1, an increase in the level of all studied profibrotic factors was revealed. After 4,7±0,3 years, repeated echocardiography revealed that selected groups were comparable in such parameters as A, E, E/A, E/e’, e’, and the peak tricuspid regurgitation velocity. There was a significant difference in left atrial volume index (p=0,0003). LV DD was detected in 20 patients. Binary logistic regression revealed the following most significant predictors of LV DD in obese patients: glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.Conclusion. Thus, the following most significant predictors of LV DD in obese patients were identified glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.

Predicting the risk of left ventricular diastolic dysfunction in obesity

Obesity may develop heart failure with preserved ejection fraction, which is based on left ventricular diastolic dysfunction (LV DD). Currently, the search for effective predictors of LV DD is extremely relevant.Aim. To assess the prognostic value of key and additional metabolic risk factors (RFs), neurohumoral and profibrotic factors in the development of LV DD in obese patients.Material and methods. The study included 149 men with general obesity. The mean age was 49,7±7,9 years. The inclusion criteria was the presence of class I-III general obesity. The average body mass index was 32,9±3,6 kg/m2. The exclusion criteria were hypertension, coronary atherosclerosis, type 2 diabetes, as well as LV DD according to transthoracic echocardiography. Depending on the presence of epicardial adiposity, patients were divided into two groups: group 1 — epicardial adipose tissue (EAT) thickness ≥7 mm (n=70), group 2 — EAT &lt;7 mm (n=31). In all patients, the following laboratory parameters were determined in blood serum using enzyme immunoassay: type I and III collagen, Procollagen I C-Terminal Propeptide (PICP), matrix metalloproteinase-3 (MMP-3), transforming growth factor β1, vascular endothelial growth factor, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, C-reactive protein (CRP), adiponectin, soluble leptin receptor, leptin, lipid parameters and free fatty acids (FFA). After 4,7±0,3 years, echocardiography was repeated in order to assess LV diastolic function.Results. Comparative analysis of metabolic risk factors revealed a significant increase in the level of total cholesterol (p=0,001), low-density lipoprotein cholesterol (LDL-C) (p&lt;0,0001), triglycerides (TGs) (p&lt;0,0001). These groups had no differences in such parameters as high-density lipoprotein cholesterol (p=0,09) and glucose (p=0,12). An increase in the level of such pro-inflammatory cytokines as TNF-α (p&lt;0,0001), CRP (p&lt;0,0001), IL-6 (p&lt;0,0001) in group 1 was revealed, while differences in IL-10 (p=0,34) levels were not significant. In group 1, there was a significant increase in leptin levels (p&lt;0,0001), a decrease in levels of adiponectin (p&lt;0,0001) and leptin receptor (p=0,001). In group 1, an increase in the level of all studied profibrotic factors was revealed. After 4,7±0,3 years, repeated echocardiography revealed that selected groups were comparable in such parameters as A, E, E/A, E/e’, e’, and the peak tricuspid regurgitation velocity. There was a significant difference in left atrial volume index (p=0,0003). LV DD was detected in 20 patients. Binary logistic regression revealed the following most significant predictors of LV DD in obese patients: glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.Conclusion. Thus, the following most significant predictors of LV DD in obese patients were identified glucose, LDL-C, triglycerides, leptin receptor, leptin, MMP-3, FFA, PICP, and EAT thickness.

Intranasal Leptin Prevents Opioid‐induced Deaths in Mice

Introduction Respiratory depression is the primary cause of morbidity and mortality related to opioids. Previous studies showed that leptin acts as respiratory stimulant and improves ventilation and upper airway obstruction induced by opioids without reducing analgesia. Our objective was to examine if the intranasal (IN) route of administration effectively delivers leptin to the brain and if leptin prevents opioid-related deaths. We hypothesized that IN leptin would reduce opioid related mortality in adult mice. Methods To determine leptin delivery to the brain, male, 12 weeks old, C57BL/6J mice, were treated with IN leptin at 1.2 mg/kg in 1% BSA (n=5) or 1% BSA (n=5) and euthanized 20 min later. Brains were harvested, the olfactory bulbs, medullas and hypotalami were isolated and quick frozen. Brain tissue was homogenized, protease inhibitors, protein concentrations were determined and leptin levels were measured by ELISA. To determine the survival probability, male C57BL/6J mice, 12 weeks of age, received IN leptin (n=26) or vehicle (n=25) at 1.2 mg/kg and 30 minutes later received a bolus of intraperitoneal (IP) morphine at 400mg/kg. Mice were monitored for 24 hours and survival time after morphine injection was recorded. Results We observed a significant increase in leptin levels 20 min after IN leptin administration compared to IN vehicle: 7.53 ng/mL vs 0 ng/mL in the olfactory bulb (p = 0.004), 0.107 ng/mL vs 0.008 ng/mL in the medulla (p=0.01), and a trend in the hypothalamus (0.291 ng/mL vs 0.018 ng/mL, p = 0.1). IN leptin improved mortality induced by morphine, 23 out of 25 mice treated with vehicle died vs 18 out 26 mice treated with IN leptin (p = 0.044). The Kaplan-Meyer curve is shown below. Conclusion We demonstrated that the intranasal route effectively delivered leptin to the brain and that IN leptin decreased opioid-induced mortality in C57BL/6J mice. Our translational data suggests that IN leptin may prevent opioid-related deaths.

Lower levels of leptin are associated with severity parameters in visceral leishmaniasis patients.

Visceral leishmaniasis (VL) is the most severe clinical form of leishmaniasis, and if untreated may be fatal. It affects important organs of the immune system and is characterized by a specific immunosuppression, along with intense cellular activation and cytokine storm. Moreover, VL is now recognized as a systemic inflammatory response syndrome (SIRS), in which multiple cytokines and other pro-inflammatory molecules are released. The action of these inflammatory mediators may be considered risk factors for poor prognosis and death. Leptin, a hormone derived from adipose tissue, has been described with several immunoregulatory functions in vitro and in vivo Leishmania infection models, particularly for enhancing the macrophage microbicidal mechanisms. Considering that evaluation of immunologic parameters that may be associated with this clinical scenario may help to decrease VL lethality, we evaluated whether leptin is associated with VL pathogenesis. Thirty-one patients were recruited in the active phase of VL, of which 22 were followed up until one month after therapy (1mpt). Except for creatinine levels, all clinical parameters were altered in active VL patients, especially leucocyte counts and albumin and hemoglobin levels. Also, elevated levels of lipopolysaccharide (LPS), immunoglobulins (Ig)G1 and G3 anti-Leishmania and interleukins (IL)-6 and -10 were higher than in healthy individuals. In contrast, active VL patients presented diminished serum leptin levels and positive correlation with leukocytes counts and hemoglobin and albumin levels. After 1mpt, VL patients showed a significant increase in leptin levels, reaching values similar to healthy volunteers. As expected, only LPS levels remained elevated after 1mpt. These findings suggest that leptin levels are affected in Leishmania infection and the correlation with important parameters associated with the prognosis of VL points to the involvement of this molecule in VL immunopathogenesis. Additional studies are needed to evaluate the possibility of leptin as a prognostic marker of VL.

Possible Critical Role of Latent Chronic Toxoplasma gondii Infection in Triggering, Development and Persistence of Autoimmune Diseases

T. gondii is globally distributed with a high proportion of the world population estimated to be seropositive, and in the U.S. the parasite is responsible for approximately million infections each year. T. gondii tachyzoites infect almost all nucleated cells and their intracellular multiplication and lifelong persistence in the host cells play an important role in triggering and development of autoimmune diseases (ADs). Latent chronic T. gondii infection may be associated with iron, iodine, and folic acid deficiencies that facilitate development and/or progression of ADs. The oral route is the natural portal of entry for the parasite and gastrointestinal manifestations are frequently reported in patients with ADs. Prolactin was found to bind to tachyzoites and this process impairs their adhesion and penetration into the host cells. Hyperprolactinemia (HPRL) demonstrated in patients with different ADs may therefore reflect host defense against T. gondii infection, and several antipsychotic drugs that induce HPRL also have antitoxoplasmatic activity. Leptin and obesity play an important role of in triggering and maintenance of inflammation and autoimmunity. T. gondii infection causes a significant increase in leptin levels and there is a significant positive association between the parasite seropositivity and obesity. Nitric oxide (NO) acts as a proapoptotic as well as an antiapoptotic biomodulator, and have a variety effects on autophagy. Overproduction of NO during T. gondii infection causes dysfunction of both these processes and therefore hinders cleaning service of the apoptotic/autophagic cell-derived antigenic remnants, finally leading to triggering and development of ADs. Damage of the olfactory system associated with chronic latent T. gondii infection may affect olfactory bulb volume and various olfactory functions, being therefore at least in part responsible for the smell impairment in ADs. The potent proinflammatory response of macrophages to infection with T. gondii type II may explain the ability of the strain to cause pathology after oral infection. The parasite also triggers the secretion of antiinflammatory cytokines, such as IL-10, TGF-b, and generation of reactive nitrogen intermediates, thus suppressing the development of the T H 1 immune responses and deactivating macrophages. Toxoplasma chronic infection-induced cytotoxic T lymphocyte exhaustion leads to development of ADs because of decreased polyfunctionality, cytotoxic capability, cytokine production, proliferative capacity, and metabolic deficiency. The process of CD4 + and CD8 + T-cell immune exhaustion inhibits the immune response, thus facilitating pathogen persistence. Systemic T. gondii infection triggers a rapid and persistent decrease in the size of naive CD4 + T lymphocyte pool, and a long-term thymic atrophy and output due to destruction of the thymic epithelium. Chronic parasite infections characterized by lower pathogen burden usually restricted to tissues, suggest alternative driving forces in the induction of T cell exhaustion, such as parasite encystations. A significantly lower occurrence of antibodies to persistent viral infections reported in patients with some ADs compared with controls may be due to suppressed (exhausted) function of host B cells. Both T. gondii- and viral-associated inflammatory processes may be mutually overlapping which lead to worsening or improving clinical course of ADs depending on final temporary or stable proinflammatory/antiinflammatory cytokine constellations. Dual-affinity T cell receptors may at least in part be responsible for frequently observed coinfections of T.gondii with some viruses and bacteria. Commonly reported comorbidities in ADs may at least in part be explained by liver damage caused by the pathogen. Vitamin D deficiency is often found in patients with ADs and there is vast evidence that the vitamin has an important beneficial impact on both innate and acquired immunity. Moreover, vitamin D exerts toxoplasmacidal effects and therefore should find a firm place in treatment regimens used in ADs.

Leptin Levels in Patients with Type 1 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant.

Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant. Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 10⁶, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure. Fetal pancreatic stem cell transplant led to significant increases in leptin and C-peptide levels, from 4.63 ± 1.17 ng/mL and 0.09 ± 0.02 ng/mL to 7.71 ± 1.45 ng/mL (P < .05) and 0.22 ± 0.05 ng/mL (P < .005), respectively, without an increase in antibodies to the islets of Langerhans, which measured 0.64 ± 0.13 U/mL before transplant and 0.57 ± 0.18 U/mL 3 months later (P > .05). Leptin levels increase significantly within 3 months of fetal pancreatic stem cell transplant in patients with type 1 diabetes mellitus.

Adipokiny, insulinorezistentnost' i aktivnost' simpato-adrenalovoy sistemy u yunoshey s ozhireniem, manifestirovavshim v pubertatnyy period

69 young men with obesity manifesting at puberty have been examined. The average age was 19,22±0,26. 17 healthy young men, whose average age was 22 ± 0,72 years old, constituted a control group. The examined were divided according to their blood pressure (BP): the first subgroup included 36 young men with normal blood pressure, the other subgroup included 33 young men with arterial hypertension. Levels of blood lipid spectrum, levels of leptin, resistin, adiponectin, insulin in serum, urinary metanephrine excretion were measured. We obtained the following results: young men with obesity identified atherogenic changes in lipid metabolism, insulin resistance and compensatory hyperinsulinemia. Regardless of the level of blood pressure they showed a significant increase in leptin levels. In the subgroup of patients with hypertension we found increased urinary excretion of metanephrine, indicating increased activity of the sympathoadrenal system and its involvement in the formation of hypertension. The level of adiponectin in the surveyed tended to decrease, more pronounced in the combination of obesity and hypertension.

Leptin promoter G–2548A genotypes and associated serum leptin levels in childhood acute leukemia at diagnosis and under high-dose steroid therapy

Genotype/allele distributions of leptin promoter G−2548A polymorphism, serum leptin and insulin levels and body weight were not significantly different between 72 children (39 male/33 female; age range 1.08–16, median 6 years) with acute leukemia (56 acute lymphoblastic leukemia [ALL]/16 acute non-lymphoblastic leukemia [ANLL]) at diagnosis and 70 age- and sex-matched controls (p > 0.05). The − 2548GG genotype was associated with the highest leptin levels in controls and patients with acute leukemia after 7-day high-dose methylprednisolone (HDMP) therapy (p < 0.05), while no significant association of genotype with leptin levels was detected in patients at diagnosis (p > 0.05). One-week HDMP therapy in patients carrying the − 2548G allele caused a significant increase in leptin levels and body weight (p < 0.001), whereas increases in those carrying the − 2548AA genotype were insignificant (p > 0.05). Decreases in white blood cell counts of patients after therapy were insignificant in − 2548GG (p > 0.05) yet significant in − 2548GA and − 2548AA (p < 0.05) genotypes. These results revealed no association of leptin genotype with the etiology of childhood acute leukemia but a possible association with leptin levels and effects of HDMP therapy.

Adiponectin and leptin serum levels in osteoporotic postmenopausal women treated with raloxifene or alendronate

Clinical studies evaluating the role of leptin and adiponectin on bone metabolism had shown conflicting results, and data about the effect of anticatabolic drugs on these adipokines are scarce. Our aims were to determine adiponectin and leptin levels in osteoporotic postmenopausal women and their relationship with bone mass and bone turnover and to analyze changes on adiponectin and leptin levels after treatment with raloxifene or alendronate. We selected 53 women (mean ± SD age, 63 ± 7 y) with postmenopausal osteoporosis divided into two treatment groups: raloxifene (60 mg/d; n = 20) or alendronate (70 mg/wk; n = 33) during a period of 1 year. Bone mineral density by dual-energy x-ray absorptiometry and serum levels of leptin, adiponectin, and bone turnovers markers were determined at baseline and at 1 year after treatment. Baseline levels of leptin were correlated to body mass index (r = 0.47; P < 0.01), waist circumference (r = 0.38, P = 0.01), and estradiol (r = 0.4, P = 0.003). Adiponectin was inversely related to bone-specific alkaline phosphatase (r = -0.41, P < 0.01) and serum crosslaps (r = -0.35; P < 0.01). There was no correlation between bone mineral density, leptin, and adiponectin. After 12 months, no changes were observed in leptin and adiponectin in the alendronate group; however, a significant increase in leptin levels (973.5 ± 637.4 pM/mL vs 1,305.7 ± 793.5 pM/mL; P = 0.031) was detected in the raloxifene group, whereas adiponectin levels showed no significant changes (P = 0.46). In postmenopausal women with osteoporosis, raloxifene induces a significant increase in leptin levels without significant changes in adiponectin serum levels. The antiresorptive effect of raloxifene and alendronate is not substantially influenced by changes in leptin or adiponectin levels.

Effect of Vitamin D Deficiency and Replacement on Endothelial Function in Asymptomatic Subjects

Vitamin D receptors are present in many tissues. Hypovitaminosis D is considered to be a risk factor for atherosclerosis. This study explores the effects of vitamin D replacement on insulin sensitivity, endothelial function, inflammation, oxidative stress, and leptin in vitamin D-deficient subjects. Twenty-three asymptomatic vitamin D-deficient subjects with 25-hydroxyvitamin D [25(OH)D] levels below 25 nmol/liter were compared with a control group that had a mean 25(OH)D level of 75 nmol/liter. The vitamin D-deficient group received 300,000 IU im monthly for 3 months. The following parameters were evaluated before and after treatment: vitamin D metabolites, leptin, endothelial function by brachial artery flow mediated dilatation (FMD), insulin sensitivity index based on oral glucose tolerance test, and lipid peroxidation as measures of thiobarbituric acid reactive substances (TBARS). FMD measurements were significantly lower in 25(OH)D-deficient subjects than controls (P = 0.001) and improved after replacement therapy (P = 0.002). Posttreatment values of TBARS were significantly lower than pretreatment levels (P < 0.001). A positive correlation between FMD and 25(OH)D (r = 0.45; P = 0.001) and a negative correlation between FMD and TBARS (r = -0.28; P < 0.05) were observed. There was a significant increase in leptin levels after therapy, and the leptin levels were positively correlated with 25(OH)D levels (r = 0.45; P < 0.05). This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFalpha, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFalpha, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

Plasma nitric oxide and leptin values in patients with olanzapine-induced weight gain

We previously investigated leptin levels in antipsychotic-induced weight gain and found that atypical antipsychotic, especially clozapine and olanzapine-induced weight gain is related to increased levels of leptin. It has been suggested that nitric oxide (NO) is a potential regulator of leptin-induced lipolysis. To explore the pathophysiology of weight gain during atypical antipsychotic treatment, we planned to investigate olanzapine’s influence on leptin and NO levels and weight gain. The study comprised 21 patients with schizophrenia who were enrolled in olanzapine monotherapy, and 21 healthy controls. The fasting plasma NO and leptin levels were measured in both patients and controls at baseline. The patients were also evaluated at sixth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), weight, serum leptin and NO levels. At baseline, the mean leptin level in the olanzapine group was not different compared to that in controls after BMI or age adjustment. A significant increase in leptin levels by means of olanzapine use was seen ( P < 0.01). Higher plasma NO levels were observed in patients with schizophrenia compared with the control group at baseline ( P < 0.01). At the evaluation of week 6, a significant decrease in the mean plasma NO level was found in the olanzapine group ( P < 0.05). The changes in total PANSS scores were correlated with change in leptin levels ( r = 0.58, P < 0.05), and with the change in weight ( r = 0.54, P < 0.05). In addition, there was a severe significant negative correlation between the changes in leptin levels and NO levels ( r = 0.73, P < 0.01). The results confirmed that leptin and NO might be associated with olanzapine-induced weight gain.

Similar Effects of General and Spinal Anaesthesia on Perioperative Stress Response in Patients Undergoing Haemorrhoidectomy

Surgery induces release of neuroendocrine hormones (cortisol), cytokines (interleukin-6: IL-6, tumour necrosis factor-α: TNF-α), acute phase proteins (C-reactive protein: CRP, leptin). We studied the effects of general and spinal anaesthesia on stress response to haemorrhoidectomy. Patients were assigned to general and spinal anaesthesia groups (n = 7). Blood samples were drawn before induction and 24 hours after surgery. Perioperative levels of IL-6, TNF-α, CRP, cortisol, and leptin were comparable among the groups. Twenty four hours after surgery, TNF-α and cortisol did not change; IL-6 and CRP increased significantly in all patients. Significant increase in leptin levels was found in patients undergoing spinal anaesthesia. Except for the increase in leptin levels, there was no significant difference related to the effects of general and spinal anaesthesia.

The effect of estradiol and progesterone application on leptin concentration in ovariectomized rats

The aim of the present study was to investigate the effects of estradiol and progesterone application on leptin secretion in ovariectomised rats. The study included 30 adult female Sprague-Dawley rats. Rats were divided into three groups as follows: Group 1; Sham ovariectomy group (n=10), Group 2; Ovariectomy group (n=10), Group 3; Ovariectomized and estradiol propionate (450 microg/kg rat) and medroxyprogesterone acetate (15 mg/kg rat) supplemented group (n=10). One week after ovariectomy, rats in Group 3 were injected estradiol and progesterone for 4 weeks. Twenty-four hours after the last injection, rats were decapitated and blood samples were collected for leptin analysis. Serum leptin levels in Group 2 were found significantly higher than those in Groups 1 and 3 (p<0.01), while those in Group 3 were significantly lower when compared to Group 1 (p<0.0 1). The findings of the present study have shown that ovariectomy led to a significant increase in leptin levels. However, administration of estradiol and progesterone in combination following ovariectomy inhibites increases of leptin levels.

Circulating leptin and the perioperative neuroendocrinological stress response after pediatric cardiac surgery

Leptin may be involved in the acute stress response, regulating inflammatory parameters of major importance after cardiopulmonary bypass (CPB) surgery. Critically ill patients demonstrated significant increases in leptin levels in response to stress-related cytokines (tumor necrosis factor, interleukin [IL]-1) and abolishment of the circadian rhythm of leptin secretion. We characterized the pattern of leptin secretion in the acute postoperative period in children undergoing cardiac surgery and compared the changes in leptin levels with concomitantly occurring changes in cortisol levels, IL-8, and clinical parameters. Investigative study. University-affiliated tertiary care hospital. Twenty-nine consecutive patients, aged 6 days to 15 yrs, operated upon for the correction of congenital heart defects were studied. Surgery in 20 patients (group 1) involved conventional CPB techniques, and 9 (group 2) underwent closed-heart surgery. The time courses of leptin, cortisol, and IL-8 levels were determined. Serial blood samples were collected preoperatively, on termination of CPB, and at six time points postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use. The leptin levels in group 1 decreased during CPB to 51% of baseline (p <.001), then gradually increased, reaching 120% of baseline levels at 12-18 hrs postoperatively (p <.001), returning to baseline levels at 24 hrs (p <.01). In patients undergoing closed-heart surgery (group 2), leptin levels displayed a pattern resembling the first group: they decreased during surgery to 71% of baseline levels (p =.002) and showed a tendency to return to baseline thereafter. All group 1 patients' cortisol levels increased significantly during the first hour of surgery, then decreased, returning to baseline levels at 18-24 hrs postoperatively. There was a significant negative correlation between leptin and cortisol levels (r = -2.8, p <.01). In group 2, cortisol levels increased during and after surgery, peaking 4 hrs postoperatively and decreasing thereafter. IL-8 levels determined in 15 group 1 patients increased significantly during CPB, peaked at the end of surgery, and then decreased but remained slightly elevated even at 48 hrs postoperatively. There was a significant correlation between cortisol and IL-8 levels (r = 2.55, p <.05). Children with leukocytosis, tachycardia, and hypotension had lower leptin levels and less variation over time as opposed to those with an uncomplicated course. CPB is associated with acute changes in circulating leptin levels. These changes parallel those in cortisol, demonstrating an inverse relationship between leptin and cortisol. Further studies of the prognostic and therapeutic roles of leptin after CPB should be investigated.

Effect of Sandostatin LAR on serum leptin levels in patients with acromegaly.

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin LAR on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin LAR and eight patients underwent transsphenoidal surgery. Serum concentrations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2.79 microg/l (2.60) vs. 4.41 microg/l (5.07); median (inter-quartile range); P < 0.01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0.46, P < 0.05) but not in the acromegalic patients before treatment (r = 0.32, ns). In the group of patients treated with Sandostatin LAR, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2.99 microg/l (2.60) vs. 4.21 microg/l (3.84), P < 0.05]. Leptin levels also significantly increased after transsphenoidal surgery [3.05 microg/l (5.73) vs. 5.19 microg/l (4.93), P < 0.05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin LAR (r = 0.62, P < 0.05) and after surgery (r = 0.81, P < 0.05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin LAR or transsphenoidal surgery led to an increase in leptin concentrations.

Lipostat in the lean rat: evidence for a non-causal relationship between glucocorticoids and leptin levels

In order to assess the long-term impact of a complete depletion of glucocorticoids on plasma leptin levels, we bilaterally adrenalectomized 20 lean rats, and analysed glucocorticoids and leptin levels for 20 consecutive days. Results demonstrate that the adrenalectomy (ADX) significantly lowered the leptin levels, as compared to sham-operated controls. On the other hand, a significant increase in leptin levels was noticeable from day 1 to day 20 of the experiment in the sham-operated controls, even though corticosterone levels remained stable during that same period. Plasma leptin concentration was proportional to body fat content. These results would indicate a non-causal relationship between glucocorticoids and leptin levels in the context of a lipostat in the lean rat.