Evaluation Of Leptin Research Articles

UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing–remitting type of multiple sclerosis

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing–remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient’s sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing–remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

Evaluation of leptin and adiponectin levels in obese patients with acne vulgaris

Evaluation of leptin and adiponectin levels in obese patients with acne vulgaris

Olanzapine- induced metabolic syndrome pathogenesis: Hypothalamic “leptin resistance” or “pomc resistance”?

IntroductionOlanzapine (OL) represents one of the main chooses for the treatment of psychosis. However, OL increase the risk of metabolic syndrome (MS). Previous literature proposes the “Leptin resistance” as a possible hypothalamic pathogenesis of OL induced MS because of the occurrence of weight gain with increased Leptin blood level.ObjectivesThe aim of our study is to investigate in a murine model of full-MS phenotype induced by Olanzapine the hypothalamic gene expression of the pathways involved in Leptin receptor signalling to clarify if a Leptin resistance occurs.MethodsFor the experiment C57BL/6Jfemale mice are used.The OL group (n=15) received pure Olanzapine compounded into chow (54 mg/kg of diet). The vehicle group (n=15)is fed with the same chow without OL. Weight gain is measured every 5 days. After 4 weeks of treatment, mice are sacrificed by rapid cervical dislocation. Blood is collected for Glucose, Insulin and Leptin evaluation. Hypothalamus is dissected and RNA-seq is performed.ResultsThe OL group shows a significantweight gain compared to Control (p= 0.02). Likewise blood glucose, Insulin and Leptin levels appear increased (p= 0,0089, p= 0,01, p= 0,0012). From the analysis of RNA-seq hypothalamic differentially expressed genes the anorexigenic POMC pathway downstream to the Leptin Receptor shows a 4-fold increased compared to control.ConclusionsIn our study the “Leptin resistance” involvement in OL induced MS is not confirmed. In fact, although there is an increase in blood Leptin, the expression of Leptin receptor downstream pathways shows a significant increase. This could suggest a possible “POMC resistance” mechanism for OL induced MS.DisclosureNo significant relationships.

M207. REVEALING HYPOTHALAMIC PATHWAYS CONTRIBUTION TO OLANZAPINE- INDUCED METABOLIC SYNDROME: FROM MURINE MODEL TO HUMAN TRANSLATION

BackgroundOlanzapine (OL) represents one of the main choices for the treatment of psychotic symptoms. However, OL increase the risk of metabolic syndrome (MS). The mechanism of Olanzapine induced MS remains still unclear but hypothalamic pathways seem to be involved. The purpose of our study is to validate an innovative approach for translational studies to investigate the hypothalamic pathways contribution to OL induced MS.MethodsTo establish a murine model of Olanzapine induced MS, OL compounded in chow (54mg/Kg of HFD food) has been administered for 30 days to C57BL/6J female mice of 10 weeks old (20 mice/group). Food intake and weight gain are tested.After the 4 weeks of treatment, mice are sacrificed by rapid cervical dislocation. Blood is collected for Glucose, Insulin and Leptin evaluation. Hypothalamus and Liver are rapidly dissected and analyzed with qPCR. Fatty liver is histologically tested with Red Oil-O- staining.The identification of mice hypothalamic coexpression network with a Genome-wide Weighted Genes Co-expression Network Analysis (WGCNA) is performed using a publicly available mice hypothalamic RNASeq a dataset.From the RNASeq data obtained from Perez-Gomez et al. study (PMID: 30532051) a differential gene expression (DGE) analysis is performed to identify the gene impacted by Olanzapine and verified with qPCR on our sample. The segregation of differentially expressed genes in specific modules of the mice hypothalamic network is tested.Human hypothalamic network identification is performed using the publicly available GTEx dataset of Hypothalamic RNASeq data for a WGCNA. The segregation of differentially expressed genes of mice model in human network has been studied. An eigengene network approach is used to study the relationship between the human affected modules.ResultsFrom the 2nd week of treatment, the weight gain shows a significant increase (p= 0.02) in OL group compared to Control. The difference in weight gain remains unchanged until the 30th day. Likewise Blood glucose, Insuline and Leptine levels appear increased in Olanzapine group compared to control (p= 0,0089, p= 0,01, p= 0,0012 respectively). The percentage of liver parenchyma occupied by lipid droplets shows a statistically significant increase in OL treated group (p=0,0001).14 of the 29 identified hypothalamic differentially expressed genes between OL- treated mice compared to control clusters in a single module of the WGCNA. The pathway analysis of this module reveals that Wnt signaling pathway reaches the statistical significance (FDR= 0,02 p value = 0,00006).The co-occurrence of OL-induced hypothalamic differentially expressed genes, previously identified in mice, is analyzed on human WGCNA on hypothalamic RNASeq data. The impacted module in humans seems to be three with no identifiable pathways involved. From the eigengene analysis results that two of the three impacted modules cluster in a single hierarchical module. The pathway analysis performed on the whole eigengine module reveals that Wnt signaling pathway reaches the statistical significance (FDR= 0,01 p value = 0,00003).DiscussionOur study firstly demonstrates the full MS-phenotype induced by Olanzapine avoiding the use of weight gain as a proxy of OL-MS as shown in previous literature. The high comparability shows by hypothalamic network analysis in mice and humans underlines the highly interspecies conservation of hypothalamic functional pathways. So the present study represents an innovative approach for translational studies on hypothalamic pathway contribution to MS induced by OL. Combining a murine model, network analysis and human translation it proposes a reliable method for translation of pre-clinical studies.

Serum evaluation of leptin, IL-6, IGF-1 and estrogen in obese bitches with early stages of mammary carcinoma

ABSTRACT The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P&lt; 0.0001). There was a positive correlation between ECC and IMCC (P&lt; 0.0001), ECC and % GC (P&lt; 0.0001), and IMCC and % GC (P&lt; 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas.

Evaluation of leptin and MMP2 genes methylation in childhood obesity

Recent novel eras of research are opening for the effective management of obesity, in general and childhood obesity, in specific through gene and nutrient intake interactions, Nutrigenomics. The causes of obesity are complex and multifactorial. Here we investigated whether Leptin/MMP2 genes promoters' methylation were associated with childhood obesity. Folic acid level was measured by ELISA, methylation state within promoters of the selected genes in extracted DNA from blood samples was evaluated by methylation-specific PCR (MS-PCR). Obese children with high weight percentile showed a highly significant hypomethylation state in Leptin/MMP2 genes' promoters when compared to the obese follow up group after folic acid intake and to age-sex matched group with normal weight percentile, (p < 0.01). Furthermore, serum folic acid level was highly significant lower in obese children when compared to control group (p < 0.01). After folic acid supplementation for 3 months (300 μg/ day), a high significant increased DNA methylation in promoters of both genes was achieved (p < 0.01). In conclusion, these observations sustain the hypothesis said that epigenetic modifications might underpin the development of obesity and related metabolic disorders. The findings also validate the use of blood samples and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to predict obesity risk. Additionally, specific DNA hypomethylation state associated with obesity may be improved by folic acid supplementations.

Evaluation of Leptin as a Marker of Insulin Resistance in Type 2 Diabetes Mellitus.

Background:Type 2 diabetes mellitus (T2DM) is a leading cause of mortality and morbidity worldwide, whose incidence is rapidly increasing in India. T2DM is caused by varying degrees of insulin resistance (IR) and relative insulin deficiency. Leptin, an adipokine with the primary function of regulating energy balance, is found to mediate insulin secretion and sensitivity in peripheral tissues. Hence, we aimed to determine the role of leptin in the development of IR in newly diagnosed T2DM patients.Aim:This study aims to compare the leptin levels and homeostatic model assessment-IR (HOMA-IR) levels in the study population.Material and Methods:The study included a total of sixty patients newly diagnosed with T2DM. Their fasting blood samples were collected to estimate the glucose, insulin, and leptin levels. IR was calculated using HOMA-IR formula. Statistical analysis was done by Pearson's correlation, Spearman's correlation, and One-sample Wilcoxon Signed Rank test.Results:Leptin and HOMA-IR levels were significantly high in T2DM patients (P < 0.001) when compared with reference values. Body mass index showed a significant positive correlations with insulin (r = 0.40, P < 0.01), HOMA-IR (r = 0.37, P < 0.01), and leptin levels (r = 0.90, P < 0.01). Leptin levels showed significant positive correlations with plasma insulin (r = 0.35, P < 0.01) and HOMA-IR levels (r = 0.31, P < 0.05). The correlation between leptin and HOMA-IR levels was more pronounced and significant among the obese T2DM subjects (r = 0.82, P = 0.01).Conclusion:Hyperleptinemia reflecting leptin resistance plays an important role in the development of IR in obeseT2DM patients, making leptin a possible biomarker for the same.

Evaluation of leptin, adiponectin, and ghrelin levels in patients with acne vulgaris.

The research evaluating adipokines are very few in patients with acne vulgaris. The hypothesis that hyperinsulinemic and high glycemic index diet plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as leptin (L), adiponectin (A), ghrelin and A levels, and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris. Thirty patients who are nonobese with moderate acne vulgaris, aged 18 to 25 years, and 15 age-sex compatible controls were included in our study. The acne lesions were assessed using the Global Acne Grading Scale (GAGS). All participants were evaluated for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood, and their body mass index were calculated. The significance level was determined as p ≤ 0.05. Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease were 2.8 years. All of patients had moderate acne vulgaris (GAGS 19-30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the two groups. Adipokines may have a role in the pathogenesis of acne vulgaris. L, A, ghrelin, and insulin resistance may not participate in the responsible mechanisms in nonobese patients with moderate acne vulgaris.

180 Evaluation of leptin and ghrelin levels in the blood serum of patients diagnosed with cystic fibrosis

Objectives Leptin and ghrelin are peptide hormones which, working antagonistically, regulate the energy balance of the body. The aim of the study was to evaluate the levels of leptin and ghrelin in the blood serum of patients diagnosed with cystic fibrosis (CF), in relation to their nutritional status and function of liver cells. Methods The study group consisted of 34 patients, aged from 3 months to 18 years (mean age 4.5 years) who were diagnosed with CF on the basis of screening and/or diagnostic tests. The analysis included the nutritional status, CFTR gene mutation, assessment of the exocrine pancreas function, abnormal lipid metabolism, as well as liver cell function parameters. In all children, serum leptin and ghrelin levels were measured by means of an immunoenzymatic test, using reagents from DRG Instruments. The results were statistically analyzed. Results Serum ghrelin levels were significantly lower in the youngest patients ( Conclusion Ghrelin and leptin levels in children with cystic fibrosis correlate with the nutritional status and can be an early marker of exocrine pancreatic insufficiency.

Evaluation of leptin, thought as a cancer-related biomarker, in postmenopausal women.

We read with great interest the article by Paxton et al. [1] entitled ‘‘Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers’’ in which the investigators reported that the associations between time spent sitting and cancer-related biomarkers were not linear, and no significant associations were found. They added that the relationships between sedentary behavior and cancer-related biomarkers may differ by important factors. We thank the authors for their detailed report. However, we wish to make some comments on leptin, which was evaluated in their study. Leptin, which is an adipocyte-secreted hormone, regulates food intake, energy homeostasis, neuroendocrine function, metabolism, and immune function [2]. Leptin shows circadian variations in its secretion [3]. Leptin rises in the afternoon, peaks at night, and decreases to basal levels in the early morning [3]. The authors did not define the sampling time. In this regard, without defining the sampling time, interpreting the results is problematic. Previous studies showed that certain diseases such as hypertension, cardiovascular diseases, major depression, chronic liver diseases, and several infectious and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Helicobacter pylori infection affect plasma leptin levels [4, 5]. The authors did not mention such contributing factors. In addition, some types of antipsychotics, antidepressants, statins, glucocorticoids, antihypertensive, and antidiabetic drugs affect plasma leptin levels [6, 7]. Also, dietary supplements such as vitamin D, vitamin E, vitamin A, omega-3 fatty acids, linoleic acid, and zinc can affect plasma leptin levels [8, 9]. Bailey et al. [10] reported that supplement use was reported by 49 % of the US population. In this respect, the authors should have stated whether the participants used such drugs and dietary supplements. In conclusion, though this study contributes valuable information to the medical literature, clarifying these concerns will certainly provide a clearer picture when interpreting leptin levels among participants.

LB029-MON: Assessment of Nutritional Status and Evaluation of Leptin, Adiponectin, C-Reactive Protein (CRP) Level in Elderly with Aortic Stenosis

LB029-MON: Assessment of Nutritional Status and Evaluation of Leptin, Adiponectin, C-Reactive Protein (CRP) Level in Elderly with Aortic Stenosis

Evaluation of leptin, interleukin–1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

To analyze serum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection. Sixty cases of malaria falciparum were included in this study as patients. Thirty healthy individuals of comparable age, racial and body mass index were taken as controls. All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film. Estimation of liver function test, kidney function test, complete blood count, fasting blood sugar, fasting serum insulin, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and interleukin 1 (IL1), estimation of morning serum leptin and calculation of body mass index (kg/m(2)) were done in both groups on the day of admission, on discharge and 7 d after discharge. At admission, leptin levels were significantly higher in patients group than in control while fasting serum insulin levels were not significantly different between the two groups. There were significant increases as regard to TNFα and IL1 in malaria patients. Significant differences were observed between the control and the patient group for leptin, TNFα and IL1 at the time of admission and discharge. After discharge for 7 d, a significant decline in serum leptin levels, TNFα and IL1 in the patients group was observed as compared with time of admission and time of discharge, a positive correlation between serum leptin levels and TNFα and IL1. Leptin hormone level might play an important role in development and outcome of malaria infection.

Evaluation of leptin and leptin receptor gene 3′ UTR polymorphisms in essential hypertension

Introduction: Leptin and leptin receptor gene polymorphisms have been associated with obesity; however, their association with blood pressure has not been fully elucidated. The aim of this study was to examine the effect of tetranucleotide repeat polymorphism in the 3′ flanking region of the leptin and leptin receptor gene on blood pressure in hypertensives with obesity.Methods: Two hundred and eighty hypertensives and 200 healthy controls were analyzed for a tetranucleotide repeat polymorphism of leptin and leptin receptor genes. Genotyping was done by amplifying DNA and determining the allele sizes using gel documentation system. Odds ratios were computed to predict the risk for hypertension caused by specific genotypes of leptin and leptin receptor genes and the effect of interaction between them on the development of hypertension was determined by MDR test.Results: Significant preponderance in the incidence of male sex, obese individuals and those with positive family history was observed with significant elevation in the mean levels of SBP, DBP, BMI and reduction of HDL levels in hypertensives as compared to controls. Class I/I genotypes of leptin showed significantly high risk for developing hypertension irrespective of obesity. Genotypes of leptin receptor did not confer any risk for hypertension and cohorts studied.Conclusion: Homozygotes I/I were at greater risk for developing hypertension irrespective of obesity. When leptin and leptin receptor genes were considered together, synergistic interaction was observed between the two genes leading to hypertension, while the polymorphism at leptin gene and obesity was correlated.

Is leptin the parabiotic “satiety” factor? Past and present interpretations

In 1959 Hervey hypothesized that a circulating feedback signal informed the hypothalamus of the size of fat stores and initiated appropriate corrections to energy balance. The hypothesis resulted from a parabiosis study in which one animal became obese following lesioning of the ventromedial hypothalamus. The partner of the lesioned rat was hypophagic and lost a large amount of body fat. Similar results came from parabiosis studies with obese Zucker rats and rats that overate due to stimulation of the lateral hypothalamus. In studies in which one parabiont was made obese by overfeeding the non-overfed partners lost substantial amounts of fat with a minimal reduction in food intake and no loss of lean tissue. The loss of fat was due to inhibition of adipose lipogenesis and other metabolic adjustments typical of food restriction. Parabiosis with genetically obese mice implied that ob/ob mice did not produce the feedback signal and subsequently the mutant ob protein, leptin, was identified. This paper provides a review and interpretation of parabiosis work that preceded the discovery of leptin, an evaluation of leptin in relation to its function as the circulating feedback signal and evidence for additional circulating factors involved in the control of adipose tissue mass.

Leptin treatment confers clinical benefit at multiple stages of virally induced type 1 diabetes in BB rats

The adipokine, leptin, regulates blood glucose and the insulin secretory function of beta cells, while also modulating immune cell function. We hypothesized that the dual effects of leptin may prevent or suppress the autoreactive destruction of beta cells in a virally induced rodent model of type 1 diabetes. Nearly 100% of weanling BBDR rats treated with the combination of an innate immune system activator, polyinosinic:polycytidylic acid (pIC), and Kilham rat virus (KRV) become diabetic within a predictable time frame. We utilized this model to test the efficacy of leptin in preventing diabetes onset, remitting new onset disease, and preventing autoimmune recurrence in diabetic rats transplanted with syngeneic islet grafts. High doses of leptin delivered via an adenovirus vector (AdLeptin) or alzet pump prevented diabetes in>90% of rats treated with pIC+KRV. The serum hyperleptinemia generated by this treatment was associated with decreased body weight, decreased non-fasting serum insulin levels, and lack of islet insulitis in leptin-treated rats. In new onset diabetics, hyperleptinemia prevented rapid weight loss and diabetic ketoacidosis, and temporarily restored euglycemia. Leptin treatment also prolonged the survival of syngeneic islets transplanted into diabetic BBDR rats. In diverse therapeutic settings, we found leptin treatment to have significant beneficial effects in modulating virally induced diabetes. These findings merit further evaluation of leptin as a potential adjunct therapeutic agent for treatment of human type 1 diabetes.

Evaluation of leptin in breast milk, lactating mothers and their infants

Leptin is present in human milk, but it is not clear what the relationship between breast milk (BM) leptin levels and maternal and infant serum leptin concentrations is. The objective of this study was to evaluate the leptin concentration in BM and to investigate its relationship with infants' and mothers' anthropometric parameters and with serum leptin concentration in breast-fed (BF) infants and lactating mothers. We enrolled 36 adequate for gestational age healthy, exclusively BF, term infants aged <6 months. Leptin concentration in serum and BM was determined by radioimmunoassay (RIA) test (human-leptin-RIA-sensitive, Mediagnost). Infants' and mothers' weights, lengths and body mass indexes (BMI) were measured. The median leptin concentration was 3.42 ng/ml (interquartile range (IR): 2.65) in BF infants' serum, 3.02 ng/ml (IR: 2.85) in mothers' serum (n=17) and 0.51 ng/ml (IR: 0.34) in BM (n=24). BM leptin concentrations were significantly lower than serum BF infant (P<0.001) and maternal (P<0.001) leptin levels. Infant serum leptin concentration correlated positively with infant weight (r=0.437, P=0.008) and BMI (r=0.561, P=0.004). Mother serum leptin levels correlated positively with weight (r=0.755, P<0.001) and BMI (r=0.661, P=0.007). No correlations were found between BM leptin and serum leptin concentrations in BF infants and mothers. We confirmed the presence of leptin in BM at a lower concentration than that found in infant and lactating mother serum. We observed a positive correlation between serum leptin levels in BF infants and their growth parameters.

Peripheral leptin and ghrelin receptors are regulated in a tissue-specific manner in activity-based anorexia

The aim of this research was to investigate the effect of long-term exposure to low leptin and high ghrelin levels, inherent to activity-based anorexia (ABA), on peripheral metabolism-implicated tissues such as muscle and fat depots. For this purpose, rats under ABA were submitted to a global study which included the characterization of body weight and composition change, the evaluation of leptin and ghrelin levels as well as their receptors expression at peripheral level. Our results confirm that feeding restriction to 1 h per day, and particularly the combination of this fasting regime with exercise ( ABA), significantly reduces fat mass, decreases leptin circulating levels, increases ghrelin levels strikingly and enhances insulin sensitivity. By direct in vitro assays, we show that visceral and gonadal fat participate more than subcutaneous fat in the hypoleptinemia of these animals. The study of ghrelin (GHS-R1a) and leptin (LEPR) receptors at peripheral level exhibits a tissue-specific expression pattern. Concretely, oxidative-soleus type of muscle appears to be more susceptible to ghrelin and leptin circulating levels than glycolytic-gastrocnemius type under exercise and food restriction situations. In relation to adipose tissue, chronic hyperghrelinemia induces GHS-R1a expression on visceral and subcutaneous fat which might suggest the prevention of lipid loss. On the other hand, only subcutaneous fat express the active long form of LEPR compared to visceral and gonadal fat under low leptin levels in ABA animals. All together, these findings indicate tissue-specific mechanisms for the control of energy homeostasis in response to nutrient and energy availability.

Chronic treatment with inhaled corticosteroids does not modify leptin serum levels.

To assess the influence of a short-term treatment with low-dose inhaled corticosteroids on leptin serum levels. 14 prepubertal children, mean age 5.1 +/- 2.4 years, treated with inhaled fluticasone propionate 100 microg b.d. and 16 prepubertal children, mean age 8.3 +/- 1.3 years, treated with inhaled budesonide 200 microg b.d. All children underwent a CRH test with evaluation of leptin, cortisol and ACTH levels before and after 3 months of treatment. Fluticasone group: no difference was found between basal cortisol level, delta and area under the curve (AUC) before and after treatment, though cortisol peak was significantly lower following treatment. Basal ACTH level, peak and AUC were significantly lower after treatment. Budesonide group: no statistically significant difference in any of the parameters regarding cortisol and ACTH secretion was observed before and after treatment. No significant changes in basal serum leptin levels and AUC were observed following treatment in both groups. Furthermore no significant variation in leptin level was observed during both CRH tests. Leptin secretion does not seem to be affected by low-dose inhaled corticosteroids; moreover leptin does not seem to be involved in the response of the HPA axis to stress.