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Copyright of Journal of University of Anbar for Pure Science is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Regular exercise and dietary supplements with antioxidants each have the potential to improve cognitive function and attenuate cognitive decline, and, in some cases, they enhance each other. Our current results reveal that low-intensity exercise (mild exercise, ME) and the natural antioxidant carotenoid astaxanthin (AX) each have equivalent beneficial effects on hippocampal neurogenesis and memory function. We found that the enhancement by ME combined with AX in potentiating hippocampus-based plasticity and cognition is mediated by leptin (LEP) made and acting in the hippocampus. In assessing the combined effects upon wild-type (WT) mice undergoing ME with or without an AX diet for four weeks, we found that, when administrated alone, ME and AX separately enhanced neurogenesis and spatial memory, and when combined they were at least additive in their effects. DNAmicroarray and bioinformatics analyses revealed not only the up-regulation of an antioxidant gene, ABHD3, but also that the up-regulation of LEP gene expression in the hippocampus of WT mice with ME alone is further enhanced by AX. Together, they also increased hippocampal LEP (h-LEP) protein levels and enhanced spatial memory mediated through AKT/STAT3 signaling. AX treatment also has direct action on human neuroblastoma cell lines to increase cell viability associated with increased LEP expression. In LEP-deficient mice (ob/ob), chronic infusion of LEP into the lateral ventricles restored the synergy. Collectively, our findings suggest that not only h-LEP but also exogenous LEP mediates effects ofME on neural functions underlying memory, which is further enhanced by the antioxidant AX. [ABSTRACT FROM AUTHOR]

In mammals, leptin production in adipocytes is up-regulated by feeding and insulin. Although this regulatory connection is central to all physiological effects of leptin, its molecular mechanism remains unknown. Here, we show that the transcription factor early growth response 1, Egr1, is rapidly but transiently induced by insulin in adipose cells both in vitro and in vivo, and its induction is followed by an increase in leptin transcription. ChIP and luciferase assays demonstrate that Egr1 directly binds to and activates the leptin promoter. Interestingly, the lipid droplet protein FSP27 may work as a co-factor for Egr1 in regulating leptin expression. By using siRNA-mediated knockout of Egr1 along with its overexpression in adipocytes, we demonstrate that Egr1 is both necessary and sufficient for the stimulatory effect of insulin on leptin transcription. [ABSTRACT FROM AUTHOR]

Aim: Leptin is produced by the adipose tissue and reduces body weight by decreasing appetite and increasing metabolism. Patients treated with antipsychotics often have treatment-induced weight-gain, leading to other metabolic complications. Obese subjects often have leptin resistance, which is defined as the presence of hyperleptinemia in obesity. We evaluated leptin resistance in subjects with schizophrenia in comparison with healthy controls of similar body composition. Methods: We determined fasting serum leptin levels and body composition parameters in 30 subjects with schizophrenia and 30 healthy, age- and sex-matched controls. Both groups were of comparable amount of body fat and lean body mass. Leptin resistance was measured as the ratio between resting energy expenditure (REE, calculated using the results of body composition analysis) and the leptin level. Results: There was no difference in the level of fasting serum leptin between the patients and the control group; there were also no differences between men in the schizophrenia and in the control groups and between women in the schizophrenia and in the control groups. Women had a significantly higher level of leptin in the schizophrenia group, in the control group and in the whole study sample (p < 0.001 for all comparisons). REE was comparable between both study groups. REE was higher in men in the whole study sample and in both study groups (p < 0.001 for all comparisons). The REE:leptin ratio did not differ between both groups. As above, the REE:leptin ratio was significantly higher in men in the schizophrenia group, in the control group and in the whole study sample (p < 0.001 for all comparisons). Conclusion: We found no differences in REE, fasting serum leptin levels and leptin resistance. However, certain differences in leptin resistance between schizophrenia patients and healthy controls may play a role in weight gain induced by antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Leptin, through binding to its special receptor (Ob-Rb), has potent effects on immunity and inflammation. This study measured the levels of leptin in the synovial fluid of patients with temporomandibular joint osteoarthritis (TMJ-OA) and healthy controls, determined the expression of Ob-Rb and explored the effects and signalling pathways involved in leptin-induced proinflammatory cytokine interleukin (IL)-6 production in TMJ synovial fibroblasts (TMJ-SFs).Methods: Synovial fluid samples were obtained from 16 patients with TMJ-OA and seven healthy controls. Leptin levels were measured in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Ob-Rb expression was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in cultured TMJ-SFs. Small interfering RNA (siRNA) was transfected into the TMJ-SFs to down-regulate the expression of Ob-Rb. qRT-PCR and ELISA were used to determine the levels of proinflammatory cytokine IL-6 in leptin-stimulated TMJ-SFs. The involved signalling pathways that mediate the leptin-stimulated production of IL-6 were investigated using specific signalling inhibitor analyses.Results: Compared with healthy controls, patients with TMJ-OA had significantly higher concentrations of leptin in their synovial fluid. The expression levels of Ob-Rb mRNA and proteins were detected in the TMJ-SFs. Leptin can stimulate the mRNA and protein expression of IL-6 in TMJ-SFs by binding with Ob-Rb. The leptin-induced production of IL-6 by the TMJ-SFs significantly decreased after exposure to siRNA targeting Ob-Rb. Inhibiting JAK2/STAT3, p38 MAPK or PI3K/Akt substantially decreased leptin-induced IL-6 production.Conclusion: Leptin may up-regulate IL-6 production in vitro by binding with Ob-Rb in TMJ-SFs via the activation of the JAK2/STAT3, p38 MAPK or PI3K/Akt signalling pathways. [ABSTRACT FROM AUTHOR]

Abstract Leptin and LPS has been implicated in the development of hypothalamic astrogliosis in rodents. Astrocytes, which are interconnected by gap junction proteins, have emerged as important players in the control of energy homeostasis exerted by the hypothalamus. To investigate the hypothesis of action of T-cell protein tyrosine phosphatase (TCPTP) on the astrocyte morphology, astrocytes from the hypothalamus of one-day-old rats were stimulated with leptin and LPS (used as a positive control). Leptin and LPS induced a marked increase in astrocyte size, an increase in Ptpn2 (TCPTP gene) and gap junction alpha-1 protein, - Gja1 (connexin 43 - CX43 gene) mRNA expression and a decrease in gap junction protein, alpha 6 - Gja6 (CX30 gene) mRNA expression. Remarkably, these effects on astrocytes morphology and connexins were prevented by Ptpn2 siRNA. Astrocytes are known to produce cytokines; here we show that TCPTP acts as an important regulator of the cytokines and it possesses a reciprocal interplay with protein tyrosine phosphatase 1B (PTP1B). Our findings demonstrate that leptin and LPS alter astrocyte morphology by increasing TCPTP, which in turn modulates connexin 30 (CX30) and connexin 43 (CX43) expression. TCPTP and PTP1B seem to act in the regulation of cytokine production in astrocytes. Highlights • Leptin act on astrocyte morphology mediated by TCPTP and to modulate connexins. • TCPTP regulates pro-inflammatory cytokines expression in the astrocytes. • TCPTP act as a negative regulator of PTP1B gene expression. [ABSTRACT FROM AUTHOR]

Highlights • A mathematical model of brain-centered glucoregulatory system is proposed. • Effects of leptin on hyperglycemia are quantified. • Leptin administration drastically improves insulin therapy. Abstract Leptin, a hormone released from fat cells in adipose tissues, was recently found to be capable of normalizing glucose metabolism in animals. Clinical data on patients with lipodystrophy indicates that leptin may have a positive effect on glucose metabolism in individuals with diabetes. There are growing expectations that leptin can improve the current insulin treatment for patients with type 1 diabetes. We investigated this possibility through in silico experiments based on a mathematical model of diabetes, which is currently the only mode of research that eliminates human risk. A model of the brain-centered glucoregulatory system, in which leptin plays a central role, was constructed and integrated within a conventional model of insulin/glucose dynamics. The model has been validated using experimental data from animal studies. The in silico combination experiments showed excellent therapeutic performance over insulin monotherapy. [ABSTRACT FROM AUTHOR]

Highlights • Depressive symptoms are inversely related to adiponectin, an anti-inflammatory, anti-atherogenic secretory protein derived from fat cells. • Compared to women with low CES-D scores, those with high CES-D scores had 7% lower adiponectin levels at baseline and 11% lower levels over 5 years. • Depressive symptoms have a dampening effect on adiponectin levels, but do not differentially affect rate of change in adiponectin over time. • Depressive symptoms and leptin were not related to each other. Abstract Small clinical studies suggest depression is associated with alterations in adiponectin and leptin, adipocyte-derived secretory proteins involved in metabolic regulation; however, longitudinal data on these association are lacking. This study examined cross-sectional and longitudinal associations of depressive symptoms and major depressive disorder (MDD) with adiponectin and leptin in healthy middle-aged women (mean (SD) age, 45.6 (2.5) years). Cross-sectional analyses included 575 women with baseline adipokine data; longitudinal analyses included 262 women with 2–4 adipokine measurements over 5 years. The 20-item Center for Epidemiologic Studies Depression scale (CES-D) was used to assess depressive symptoms; history of MDD was determined by the Structured Clinical Interview for DSM-IV. Adipokines were assayed from stored serum specimens; values were log-transformed for analyses. Linear and repeated measure random effects regression models evaluated associations of baseline CES-D scores with baseline adipokine concentrations and changes over time, respectively. Secondary analyses evaluated the relation of MDD history with adipokine concentrations. Mean (SD) baseline concentrations of adiponectin and leptin were 9.90 (4.92) μg/mL and 27.02 (20.06) ng/mL; both increased over time (p <.0001). CES-D scores were associated with lower adiponectin at baseline (per 1-SD: estimate=-0.04, SE=.02, p=.03) and over time (per 1-SD: estimate=-0.055, SE =.024, p=.02). Associations were unchanged in risk factor-adjusted models. Women with elevated CES-D scores (≥16) had 6.9% (95% CI: −1.1%, 14.3%; p =.089) lower median adiponectin at baseline and 11.5% (95% CI: 1.5%, 20.4%, p =.025) lower median adiponectin over time in adjusted models, compared to women with CES-D<16. Rate of change in adipokines did not vary by baseline depressive symptoms or MDD history. Depressive symptoms and MDD history were unrelated to leptin. In women at midlife, depressive symptoms are associated with lower adiponectin, a critical anti-inflammatory biomarker involved in metabolic and cardiovascular conditions. [ABSTRACT FROM AUTHOR]

Abstract Adipokines secreted by fatty tissue have inflammatory properties and are suggested biomarkers of MS disease activity. To assess this, 88 MS patients were followed with nine repeated measurements of leptin and adiponectin and 12 magnetic resonance imaging (MRI) scans for two years; six months without any immunomodulatory treatment followed by 18 months during interferon-beta (IFNB) treatment. Serum levels of leptin dropped and adiponectin increased upon initiation of IFNB-therapy, but were not associated with clinical or MRI disease activity or with treatment response. Our findings indicate that leptin and adiponectin are not useful as biomarkers of MS disease activity. Highlights • Serum levels of leptin were lower and serum levels of adiponectin were higher during IFNB-treatment compared to before. • There was no association between serum levels of leptin or adiponectin and MRI- or clinical activity. • Serum levels of leptin and adiponectin could not predict clinical relapses or treatment-response. • Fewer of the overweight patients obtained NEDA-status, but this was not explained by serum levels of adipokines. [ABSTRACT FROM AUTHOR]

Objectives: It is well-documented that obesity participated in the development of renal cell carcinoma (RCC). Leptin is closely associated with obesity. This study is aimed to investigate the relationship between leptin level and RCC susceptibility and progression.Methods: A meta-analysis was conducted to explore the association between leptin level and RCC susceptibility and progression. The studies were retrieved from electronic databases during January 1990-September 2017 with keywords. The qualified studies were screened with inclusion and exclusion criteria. A random effects model was applied to calculate the pooled standard mean differences and the corresponding confidence intervals.Results: Ten studies were finally included in this meta-analysis. The serum leptin level in male RCC was significantly lower than that of in female RCC in overall populations, Asians, and Caucasians while no marked difference was noted between genders in the plasma samples. Plasma leptin level in Stage I-II RCC was significantly higher than that in the Stage III-IV. In addition, no significant difference was observed between following parameters, including RCC and non-RCC, clear and non-clear RCC, Grade I-II and Grade III-IV RCC, M0 and M1 RCC, N0 and N1 RCC, and size <4 cm and size >4 cm RCC. No evidence of publication bias was observed.Conclusions: Our findings indicated that serum leptin level was lower in men with RCC than in women with RCC. Leptin level may not be related to the risk and progression of RCC. However, more studies should be performed in the future. [ABSTRACT FROM AUTHOR]

Copyright of Jornal of Al-Muthanna for Agricultural Sciences is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Leptin plays a pivotal role in the central control of energy balance through leptin receptors expressed on specific hypothalamic nuclei. Leptin suppresses food intake and body weight and ameliorates hyperglycemia by acting on the AgRP and POMC neurons of the arcuate nucleus. Leptin action on POMC neurons are essential for control of body weight and blood glucose levels and are known to be mediated by JAK-STAT3 and PI3K signalling pathway thus increase POMC mRNA and intrinsic excitability. The effects of leptin on AgRP neurons are not as clear although it has been reported to hyperpolarize AgRP neurons through change of K + conductance. Using cell-attached patch and whole cell patch configuration, we directly assessed neuronal response to leptin in GFP labelled AgRP or POMC neurons in mice after 18 h of food deprivation. We found leptin has a direct effect on POMC neuron through increased intrinsic excitability and decreased inhibitory synaptic inputs. However, leptin does not have any effect on intrinsic excitability of AgRP neurons in fasted condition although food deprivation induced increase of firing frequency of AgRP neurons. In conclusion, leptin probably has a direct and acute effect on POMC neurons but not on AgRP neurons to control their excitability within feeding-regulatory neuronal circuitry. [ABSTRACT FROM AUTHOR]

The effects of hyperleptinemia and leptin resistance during gestation are unclear. Leptin, an important neuroendocrine regulator, has anorexic effects, but its interactions with other metabolic hormones during pregnancy are unclear. We examined potential roles of leptin in regulating prolactin (PRL), GH, and melatonin plasma concentrations during pregnancy in Polish Longwool ewes. Twelve estrus-synchronized ewes carrying twins after mating were randomly assigned to receive i.v. injections of saline or recombinant ovine leptin (2.5 or 5.0 µg/kg BW). Blood samples were collected (15-min intervals over 4 h) immediately before the first injection at dusk and kept under red light. Treatments were repeated at 2-wk intervals, starting before mating and continuing from days 30 to 135 of gestation. Concentrations of plasma PRL, GH, and melatonin were determined using a validated RIA. The effects of leptin on hormone plasma concentrations varied depending on pregnancy stage and leptin dose. PRL plasma concentrations were affected at most stages of pregnancy and before gestation. In non-, very early- (day 30), and late- (day 120 and 135) pregnant ewes, exogenous leptin stimulated PRL (P < 0.001) plasma concentrations, while during the second month of gestation, it decreased PRL concentrations (P < 0.01). Leptin affected GH plasma concentrations (P < 0.05) only during the first 2 mo of pregnancy, with no effects during the second part of gestation or before pregnancy. In early- pregnant ewes (day 30 and 45), leptin decreased melatonin plasma concentrations (P < 0.05), but at day 60, leptin stimulated melatonin plasma concentrations at low (P < 0.01) and high doses (P < 0.05), with no effects in ewes after 105 d of gestation. These data indicate specific pregnancy- induced endocrine adaptations to changes in energy homeostasis, supporting the hypothesis that leptin affects PRL, GH, and melatonin release during gestation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the association between the severity of obstructive sleep apnea (OSA) and the serum leptin level in non-obese OSA patients.Methods: This prospective case-control study included non-obese OSA patients that presented with sleep-related disturbances and underwent polysomnography (PSG) between April 2015 and June 2016. The serum leptin level was measured and its relationship to PSG parameters was investigated.Results: The study included 73 OSA patients (20 female and 53 male) with a mean age of 41.1±11.5 years and mean body-mass index (BMI) of 26.4±2.7kgm-2. The serum leptin level in 44 patients with moderate/severe OSA (AHI ≥15) was 3.4±2.6ngmL-1, versus 4.5±3.8ngmL-1 in 29 patients with snoring/mild OSA (AHI <15) (P=0.20). There were not any correlations between any of the PSG parameters and the serum leptin level, but there was a significant correlation between the leptin level and BMI (r=0.345, P<0.01).Conclusion: The serum leptin level does not differ significantly between non-obese OSA patients with moderate/severe and snoring/mild OSA. Obesity is the primary factor associated with the serum leptin level. [ABSTRACT FROM AUTHOR]

Aim. There is scarce information on associations of adipokines, and concurrent glucose disposal during early pregnancy as performance of oral glucose tolerance is uncommon before 24th gestational week. We sought to examine associations of leptin and adiponectin to insulin sensitivity already at early pregnancy before recommended screening for GDM and to describe trajectories of adiponectin in relation to GDM status. Methods. 216 pregnant women were prospectively included at 16th (IQR: 14–18) gestational week (GW) for fasting adiponectin and leptin with subsequent OGTT testing for evaluation of insulin sensitivity and β-cell function. Follow-ups of adiponectin were performed at further four visits until 8–12 weeks after delivery. Results. In early pregnancy, differences in adiponectin and leptin were significant between GDM women (n=82) and controls (n=134), whereby those with early GDM (<21st week, n=49) showed more distinguishing levels (adiponectin: 8.5 ± 3.8 versus 10.4 ± 4.4 μg/ml, p=0.004; leptin 93.4 ± 38.5 versus 78.0 ± 39.2 μg/ml, p=0.005). Both adipokines were significantly associated with insulin sensitivity and β-cell function. Their attribution for GDM prediction was moderate to fair and more enhanced in early GDM. Trajectories of adiponectin remained constantly lower in GDM women, whereas dynamics in controls showed initially increased concentrations with decreasing tendency until 3rd trimester. After delivery, low adiponectin was associated with glucose dysregulation. Conclusion. Associations of adiponectin and leptin with features of deteriorated glucose metabolism at early gestation may be indicative for the endocrine involvement of adipose tissue in the manifestation of GDM and thus predictive for later impairments in metabolic flexibility in women at risk. [ABSTRACT FROM AUTHOR]

Insulin potentiates leptin effects on muscle accrual and glucose homeostasis. However, the relationship between leptin's central effects on peripheral insulin sensitivity and the associated structural changes remain unclear. We hypothesized that central leptin infusion modifies muscle size through activation of insulin signaling. Muscle insulin signaling, enzymes of fatty acid metabolism, mitochondrial respiratory chain complexes, proliferating cell nuclear antigen (PCNA) and fiber area were analyzed in the gastrocnemius of chronic central infused (L), pair-fed (PF) and control rats. PCNA-positive nuclei, fiber area, GLUT4 and glycogen levels and activation of Akt and mechanistic target of rapamycin were increased in L, with no changes in PF. Acetyl-CoA carboxylase-β mRNA levels and non-esterified fatty acid and triglyceride content were reduced and carnitine palmitoyltransferase-1b expression and mitochondrial complexes augmented in L. These results suggest that leptin promotes an increase in muscle size associated with improved insulin signaling favored by lipid profile. [ABSTRACT FROM AUTHOR]

Leptin has shown positive effects on respiratory function in experimental settings. The role of leptin on perioperative respiratory function in morbidly obese patients has not been established. We performed a retrospective analysis of morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Fasting serum leptin and interleukin (IL)-6 were measured preoperatively, and arterial blood gases were obtained pre- and postoperatively. Outcome variables were arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and differences in PaO2 and PaCO2 between pre- and postoperative values (ΔPaO2, ΔPaCO2; postoperative minus preoperative). Patients with lower (<40 μg/L) and higher (≥40 μg/L) leptin levels were compared. Bravais-Pearson’s correlation, multiple linear regression, and logistic regression analysis were performed. A total of 112 morbidly obese patients were included. Serum leptin was significantly higher in females than in males (42.86±12.89 vs. 30.67±13.39 μg/L, p<0.0001). Leptin was positively correlated with body mass index (r = 0.238; p = 0.011), IL-6 (r = 0.473; p<0.0001), and ΔPaO2 (r = 0.312; p = 0.0008). Leptin was negatively correlated with preoperative PaO2 (r = -0.199; p = 0.035). Preoperative PaO2 was lower, ΔPaCO2 was smaller, and ΔPaO2 was greater in the high leptin group than in the low leptin group. In multiple regression analysis, leptin was negatively associated with preoperative PaO2 (estimate coefficient = -0.147; p = 0.023). In logistic regression analysis, leptin was associated with improved ΔPaO2 (odds ratio [OR] = 1.104; p = 0.0138) and ΔPaCO2 (OR = 0.968; p = 0.0334). Leptin appears to have dual effects related to perioperative gas exchange in obese patients undergoing bariatric surgery. It is associated with worse preoperative oxygenation but improved respiratory function after surgery. [ABSTRACT FROM AUTHOR]

It is from the discovery of leptin and the central nervous system as a regulator of bone remodeling that the presence of autonomic nerves within the skeleton transitioned from a mere histological observation to the mechanism whereby neurons of the central nervous system communicate with cells of the bone microenvironment and regulate bone homeostasis. This shift in paradigm sparked new preclinical and clinical investigations aimed at defining the contribution of sympathetic, parasympathetic, and sensory nerves to the process of bone development, bone mass accrual, bone remodeling, and cancer metastasis. The aim of this article is to review the data that led to the current understanding of the interactions between the autonomic and skeletal systems and to present a critical appraisal of the literature, bringing forth a schema that can put into physiological and clinical context the main genetic and pharmacological observations pointing to the existence of an autonomic control of skeletal homeostasis. The different types of nerves found in the skeleton, their functional interactions with bone cells, their impact on bone development, bone mass accrual and remodeling, and the possible clinical or pathophysiological relevance of these findings are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore the correlation of insulin resistance (IR) and leptin with inflammatory factors and vascular endothelial injury in patients with type 2 diabetes mellitus (T2DM) complicated with coronary heart disease (CHD) was explored. One hundred and fifty normal patients (normal group), 150 patients with pure T2DM (T2DM group) and 150 patients with T2DM complicated with coronary heart disease (T2DM + CHD group) were selected from Xi'an No. 5 Hospital. All the participants met our inclusion criteria. Age, body mass index, waist-to-hip ratio, blood lipid and fasting plasma glucose (FPG), of all the subjects were measured. Chemiluminescent immunoassay was adopted for the detection of FPG and double-antibody sandwich method was used for the determination of fasting plasma leptin, and assay of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Insulin resistance index (IRI) was used to evaluate IR and enzyme-linked immunosorbent assay was adopted for the detection of von Willebrand factor (vWF) and endothelin (ET-1). Compared with the control group, patients in the T2DM + CHD group and those in the T2DM group had higher homeostasis model assessment-IR, and higher assay of plasma leptin, hs-CRP, IL-6 and TNF-α (P<0.05), and lower vascular endothelial function (P<0.05). Moreover, compared with the T2DM group, T2DM + CHD group had higher plasma leptin, and higher assay of hs-CRP, IL-6 and TNF-α (P<0.05). IRI was positively correlated with hs-CRP (r=0.521, P=0.001), IL-6 (r=0.359, P=0.001) and TNF-α (r=0.386, P=0.001), leptin was positively correlated with hs-CRP (r=0.305, P=0.001), IL-6 (r=0.259, P=0.002) and TNF-α (r=0.429, P=0.001), and IRI had no correlation with ET-1 (r=0.058, P=0.734) and vWF (r=0.047, P=0.812), that is, it had no direct correlation with vascular endothelial function. Level of leptin was positively correlated with ET-1 (r=0.366, P=0.001) and vWF (r=0.471, P=0.001), that is, it was negatively correlated with vascular endothelial function. Our results showed that leptin, hs-CRP, IL-6 and TNF-α are involved in the occurrence and development of CHD in patients with T2DM. IR has no direct correlation with the occurrence and development of CHD in patients with T2DM. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that diet and body weight are important factors associated with Alzheimer's disease (AD), with a significant increase in AD risk linked to mid-life obesity, and weight loss frequently occurring in the early stages of AD. This has fuelled interest in the hormone leptin, as it is an important hypothalamic regulator of food intake and body weight, but leptin also markedly influences the functioning of the hippocampus; a key brain region that degenerates in AD. Increasing evidence indicates that leptin has cognitive enhancing properties as it facilitates the cellular events that underlie hippocampal-dependent learning and memory. However, significant reductions in leptin's capacity to regulate hippocampal synaptic function occurs with age and dysfunctions in the leptin system are associated with an increased risk of AD. Moreover, leptin is a potential novel target in AD as leptin treatment has beneficial effects in various models of AD. Here we summarise recent advances in leptin neurobiology with particular focus on regulation of hippocampal synaptic function by leptin and the implications of this for neurodegenerative disorders like AD. This article is part of the Special Issue entitled ‘Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.’ [ABSTRACT FROM AUTHOR]

Anti-Müllerian hormone (AMH), insulin-like growth factor 1 (IGF1) and leptin are produced in the granulosa cells of follicles and play an important role in the growth and maturation of follicles. The aim of our study was to monitor AMH, IGF1 and leptin levels in a group of healthy women and compare them to a group of women with fertility disorders. The second aim was the evaluation of biomarker levels in relation to the identified cause of infertility. Totally, 146 females were enrolled into our study. Seventy-two healthy controls and seventy-four females with fertility disorders were divided into four subgroups: anovulation, endometriosis, fallopian tube damage, unknown reason. IGF1 was the only biomarker with significantly lower levels throughout the entire group with fertility disorders. We did not identify any statistically significant differences for AMH and leptin. Regarding subgroups, significant differences were only observed in the group of anovulatory women. AMH and leptin showed higher levels while IGF1 showed lower levels. In conclusion, levels of AMH, IGF1 and leptin found in follicular fluid are sensitive markers for anovulatory fertility disorders. AMH, IGF1 and leptin levels in follicular fluid have no relation to the fertility disorders caused by endometriosis, fallopian tube damage or disorders with unknown etiology. Abbreviations: AMH: anti-Müllerian hormone; IGF1: insulin-like growth factor 1; PCOS: polycystic ovary syndrome [ABSTRACT FROM AUTHOR]

Aim: Leptin, synthesised by adipocytes, has been identified as a hormone that can influence inflammatory activity. Several studies have investigated leptin levels in patients with multiple sclerosis (MS), but the results are not consistent. This study aims to derive a more precise evaluation on the relationship between circulating leptin levels and MS.Design: A comprehensive literature searched up to July 2017 was conducted to evaluate the association of circulating leptin levels and MS. The random-effect model was applied to calculate pooled standardised mean difference (SMD) and its 95% CI.Main Outcome Measures: Circulating leptin levels of patients with MS and healthy controls.Results: Of 2155 studies identified, 33 met eligibility criteria and 9 studies with 645 patients with MS and 586 controls were finally included in the meta-analysis. Meta-analysis revealed that, compared with the healthy control group, the MS group had significantly higher plasma/serum leptin levels, with the SMD of 0.70% and 95% CI (0.24 to 1.15). Subgroup analyses suggested that the leptin levels of patients with MS were associated with region, age, study sample size, measurement type, gender and blood sample type.Conclusion: Overall, our study suggests that patients with MS have a significantly higher leptin level than in healthy controls. Further mechanism studies and longitudinal large cohort studies are still needed to further reveal the role of leptin in the pathogenesis of MS. [ABSTRACT FROM AUTHOR]

Leptin is a hormone synthesized and secreted primarily in adipose cells that help to regulate energy balance. This study examined the associations of single nucleotide polymorphisms in the rabbit leptin gene with growth traits, slaughter traits and physicochemical parameters of New Zealand White (NZW) and Belgian Giant Grey (BGG) crossbreed rabbits. In total, 320 crossbreed animals were genotyped for polymorphisms within exon 2—g.16081633T>C,intron 1_2—g.16081420C>T,and within UTR—g.16079636C>Gfor association analysis. Identified polymorphisms within rabbits leptin gene showed significant differences for dissectible fat percentage in carcass and dissectible fat weight in intermediate part (g.16081633T>C). Moreover, meat traits like protein content (g.16081633T>C; g.16079636C>G), intramuscular fat content (g.16081633T>C; g.16079636C>G, g.16081420C>T), dry matter (g.16081420C>T),ash (g.16081420C>T),water (g.16081420C>T),and cohesiveness (g.16081420C>T, g.16079636C>G) were affected by polymorphisms in leptin gene. We conclude that polymorphism in the rabbit leptin gene influences important carcass and meat traits of NZW × BGG crossbreeds. Therefore, polymorphisms identified in this study may be used in selection as a meat trait markers. [ABSTRACT FROM AUTHOR]

Background Crack-cocaine is an important public health problem in Brazil and worldwide. It is a potent form of cocaine which results in rapid and damaging stimulating effects on the central nervous system through inhibition of the dopamine transporter. Some studies have suggested that both food and drugs – including crack, can act on the same brain reward mechanisms, altering the dopamine pathways that modulate behavioral responses. Our hypothesis was that leptin, a well-known peptide that modulates energy metabolism and appetite, can be used as a biomarker for drug use. Methods Anthropometric data, drug use profiles, and leptin serum levels were evaluated in a cross-sectional study of 40 crack-cocaine users. Results Leptin showed an inverse correlation with the severity of crack use, and this correlation remained when corrected by body mass index (BMI) and body composition by bioimpedance (BIA). The majority of subjects were eutrophic or overweight/obese considering BMI and BIA, and these variables were not significantly associated with the severity of crack use, but positively correlated with leptin levels. Conclusions Our preliminary findings suggest that leptin could be involved in drug use severity, perhaps through pathways similar to those whereby it modulates food intake. Considering the anthropometric parameters, these findings provide additional evidence that low weight is not predominant in crack users. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is developed by lack of insulin secretion or reduction of tissues sensitivity to insulin, which lead to serious complications. The aim of this study is to evaluate antihyperlipidemic effect of betulinic acid (BA) on streptozotocin-nicotinamide (STZ-NA) induced diabetic mice. In this experimental study, seventy adult male NMRI mice (20-25 g) were divided randomly into seven groups (n = 10) of control, sham, diabetes, diabetes + BA (10, 20 and 40 mg/kg), and diabetes + metformin (200 mg/kg). Diabetes was induced by intraperitoneal (i.p.) injection of a single dose of STZ (50 mg/kg) 15 min after an i.p. administration of nicotinamide (NA) (120 mg/kg). BA and metformin were orally administered and after two weeks blood samples were taken. Blood levels of leptin, adiponectin, lipid profile and liver enzyme were then measured. One day after the last drug administration, liver was removed to evaluate the histological changes. A significant increase (P < 0.05) in the plasma levels of leptin, alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), alkaline phosphatase (ALP), low density lipoprotein cholesterol (LDL-C), cholesterol, and a significant decrease in adiponectin and high density lipoprotein cholesterol (HDL-C) were observed in diabetic mice. The groups treated with BA indicated a significant decrease in leptin, AST, ALT, ALP, TG, cholesterol, LDL-C and an increases in adiponectin and HDL levels, while VLDL did not show significant changes. BA was found to have positive effects on liver injury. BA has an effective role on liver damage induced by diabetes through amelioration of leptin, adiponectin, liver enzyme levels and lipid profile. Since BA has a positive effect on lipid profile, adiponectin and leptin, it may improve metabolic syndrome. [ABSTRACT FROM AUTHOR]

Summary: This study examines the effect of melatonin on leptin‐induced changes in transition of histone to protamine in adult rats during spermatogenesis. Twelve‐week‐old Sprague‐Dawley rats were randomised into control, leptin‐, leptin–melatonin‐10‐, leptin–melatonin‐20‐ and melatonin‐10‐treated groups with six rats per group. Leptin was given via intraperitoneal injections (i.p.) daily for 42 days (60 μg/kg body weight). Rats in the leptin‐ and melatonin‐treated groups were given either 10 or 20 mg day−1 kg−1 body weight of leptin in drinking water. Melatonin‐10‐treated group received only 10 mg of melatonin day−1 kg−1 body weight in drinking water for 42 days. Control rats received 0.1 ml of 0.9% saline. Upon completion of the treatment, sperm count, morphology and histone‐to‐protamine ratio were estimated. Gene expression of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1, PRM2, TNP1 and TNP2 was determined. Data were analysed using ANOVA. Sperm count was significantly lower, whereas the fraction of spermatozoa with abnormal morphology, the ratio of histone‐to‐protamine transition and the expressions of HAT, HDAC1, HDAC2, H2B, H2A, H1, PRM1 were significantly higher in leptin‐treated rats than those in controls or melatonin‐treated rats. It appears that exogenous leptin administration adversely affects histone‐to‐protamine transition, which is prevented by concurrent administration of melatonin. [ABSTRACT FROM AUTHOR]

Leptin, an adipocyte-derived cytokine associated with bone metabolism, is believed to play a critical role in the pathogenesis of heterotopic ossification (HO). The effect and underlying action mechanism of leptin were investigated on osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro and theHOformation in rat tendons. Isolated rat TDSCs were treated with various concentrations of leptin in the presence or absence of mTORC1 signaling specific inhibitor rapamycin in vitro. A rat model with Achilles tenotomy was employed to evaluate the effect of leptin onHOformation together with or without rapamycin treatment. In vitro studies with TDSCs showed that leptin increased the expression of osteogenic biomarkers (alkaline phosphatase, runt-related transcription factor 2, osterix, osteocalcin) and enhanced mineralization of TDSCs via activating the mTORC1 signal pathway (as indicated by phosphorylation of p70 ribosomal S6 kinase 1 and p70 ribosomal S6). However, mTORC1 signaling blockade with rapamycin treatment suppressed leptin-induced osteogenic differentiation and mineralization. In vivo studies showed that leptin promoted HO formation in the Achilles tendon after tenotomy, and rapamycin treatment blocked leptin-inducedHOformation. In conclusion, leptin can promote TDSC osteogenic differentiation and heterotopic bone formation via mTORC1 signaling in both vitro and vivo model, which provides anewpotential therapeutic target forHO prevention. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze whether clozapine serum concentration may affect fasting serum levels of several appetite regulating peptides: CART, PYY(1-36), NPY, AgRP, des-acylated ghrelin, leptin and obestatin. Serum concentration of clozapine and fasting serum levels of des-acylated ghrelin, neuropeptide Y (NPY), agouti-related protein (AgRP), peptide YY (PYY(1-36)), cocaine- and amphetamine-regulated transcript (CART), leptin and obestatin were measured in 30 subjects with schizophrenia on clozapine monotherapy. Leptin concentration was negatively correlated with clozapine dose (r = −0.53, p = 0.002), while NPY concentration was negatively correlated with clozapine concentration (r = −0.55, p = 0.01). Correlations with other peptides were not significant. We cannot conclude that serum concentration of clozapine is directly associated with increased or decreased level of appetite-regulating peptides. [ABSTRACT FROM AUTHOR]

Abstract: Leptin is now considered an important signalling molecule of the reproductive system, as it regulates the production of gonadotrophins, the blastocyst formation and implantation, the normal placentation, as well as the foeto‐placental communication. Leptin is a peptide hormone secreted mainly by adipose tissue, and the placenta is the second leptin‐producing tissue in humans. Placental leptin is an important cytokine which regulates placental functions in an autocrine or paracrine manner. Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes such as proliferation, protein synthesis, invasion and apoptosis in placental cells. Furthermore, deregulation of leptin levels has been correlated with the pathogenesis of various disorders associated with reproduction and gestation, including polycystic ovary syndrome, recurrent miscarriage, gestational diabetes mellitus, pre‐eclampsia and intrauterine growth restriction. Due to the relevant incidence of the mentioned diseases and the importance of leptin, we decided to review the latest information available about leptin action in normal and pathological pregnancies to support the idea of leptin as an important factor and/or predictor of diverse disorders associated with reproduction and pregnancy. [ABSTRACT FROM AUTHOR]

Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells. The leptin expression is induced involving the cAMP/PKA or cAMP/Epac pathways which have profound actions upon human trophoblast function. The activation of PI3K and MAPK pathways also participates in the leptin expression. Estrogens play a central role during pregnancy, particularly 17ß-estradiol upregulates the leptin expression in placental cells through genomic and non-genomic actions. The leptin promoter analysis reveals specific elements that are active in placental cells. The transcription factors CREB, AP1, Sp1, NFkB and the coactivator CBP are involved in the placental leptin expression. Moreover, placental leptin promoter is a target of epigenetic marks such as DNA methylation and histone acetylation that regulates not only the leptin expression in placenta during pregnancy but also determines the predisposition of acquiring adult metabolism diseases. Taken together, all these results allow a better understanding of leptin function and regulatory mechanisms of leptin expression in human placental trophoblasts, and support the importance of leptin during pregnancy and in programming adult health. [ABSTRACT FROM AUTHOR]

Obesity escalates at an alarming rate worldwide. It is associated with chronic low-grade inflammation, which is implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. Adipose tissue is a primary site of obesity-induced pro-inflammatory factors such as leptin. Curcuminoids are potent anti-inflammatory agents; however, evidence on the polar fraction of Curcuma longa is scarce and the effect on leptin release has never been investigated. Therefore, we will investigate the influence of aqueous C. longa extract on leptin release from human subcutaneous adipose tissue (SAT). To achieve this, SAT explants were obtained from patients who underwent abdominal surgery. Patients were both males (67%) and females (33%). Their average body mass index (BMI) and age were 33.4 kg/m2 and 43 years, respectively. Tissue explants were treated in triplicate with or without 0.1 and 1 mg/mL aqueous C. longa extracts and incubated for 24 and 48 h. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of leptin secreted by SAT. We have shown that 24 h treatment of SAT with 0.1 and 1 mg/mL of C. longa polar extract inhibited the release of leptin, while 48 h treatment of SAT with only 1 mg/mL of C. longa polar extract inhibited leptin release. Concentration of basal leptin released from SAT derived from females was higher than from males. However, this could be because females were morbidly obese. Our data demonstrate for the first time the inhibitory effect of aqueous C. longa extract on leptin release, shedding light on the role of leptin and adipose tissue in the mechanism of C. longa in reducing low-grade inflammation. This avoids the poor solubility and consequently the low bioavailability disadvantages of curcuminoids. [ABSTRACT FROM AUTHOR]

Leptin is an adipocyte-derived hormone and maintains adipose function under challenged conditions. Autophagy is also essential to maintain cellular homeostasis and regulate characteristics of adipose tissue. However, the effects of leptin on autophagy of adipocyte remain elusive. Here, we demonstrated endoplasmic reticulum (ER) stress and leptin were correlated with autophagy and inflammation by transcriptome sequencing of adipose tissue. Leptin-mediated inhibition of autophagy was involved in upstream reduction of ER stress proteins such as Chop, GRP78, and Atf4, since blockage of autophagy using pharmacological approach had no effect on tunicamycin-induced ER stress. Moreover, we determined KLF4, the potential transcriptional factor of Atf4, was required for the leptin-mediated autophagy in the regulation of adipocyte inflammation. Importantly, ATF4 physically interacted with ATG5 and subsequently formed a complex to promote adipocyte autophagy. Further analysis revealed that Atg5, a core component of autophagosome, was the target for leptin-mediate autophagy. In addition, leptin alleviated ER stress-induced inflammation by reducing autophagy-mediated degradation of IκB in adipocytes. Exogenous leptin treatment also ameliorated autophagy and inflammation of white adipose tissue in ob/ob mice. Taken together, our results indicated that leptin inhibited ER stress-mediated autophagy and inflammation through the negatively regulation of Atf4/Atg5 complex in adipocytes. These findings identify a new potential means for intervention of autophagy to prevent or treat obese caused metabolic syndrome of mammals. [ABSTRACT FROM AUTHOR]

Obesity is a multifactorial disease characterized by the abnormal or excessive fat accumulation, which is caused by an energy imbalance between consumed and expended calories. Obesity leads to an inflammatory response that may result in peripheral and central metabolic changes, including insulin and leptin resistance. Insulin and leptin resistance have been associated with metabolic and cognitive dysfunctions. Obesity and some neurodegenerative diseases that lead to dementia affect mainly women. However, the effects of diet-induced obesity on memory consolidation in female rats are poorly understood. Therefore, the aim of this study was to evaluate the effect of a hypercaloric diet on the object recognition memory of female rats and on possible related metabolic changes. The animals submitted to the hypercaloric diet presented a higher food intake in grams and in calories, resulting in increased weight gain and liposomatic index in comparison with the animals exposed to the control diet. These animals presented a memory deficit in the object recognition test and increased serum levels of glucose and leptin. However, no significant differences were found in the serum levels of insulin, TNF-α and IL-1β, in the index of insulin resistance (HOMA), in the hippocampal levels of insulin, TNF-α and IL-1β, as well as on Akt expression or activation in the hippocampus. Our findings indicate that adult female rats submitted to a hypercaloric diet present memory consolidation impairment, which could be associated with diet-induced weight gain and leptin resistance, even without the development of insulin resistance. [ABSTRACT FROM AUTHOR]

Purpose: There are no data showing a direct correlation between obesity and increased blood leptin levels with folliculoma. Moreover, folliculoma is not the best studied among other ovarian cancer types. We investigated whether oestradiol can modulate ObR expression in some oestrogen-responsive tissues and that leptin exerts its activity not only via the leptin receptor but also through cross talk with other signalling systems. We hypothesise that blocking ObR expression could be a novel treatment for gonadal ovarian cancer.Methods: We evaluated the effect of SHLA, Lan1 and Lan2 blockers on cell proliferation (BrdU incorporation assay), ObR and ERα/β gene expression (qPCR), oestradiol secretion (ELISA) and cell cycle protein expression (Western blot) in the non-cancerous cell line HGrC1 and two granulosa cancer cell lines: the juvenile form (COV434) and the adult form (KGN).Results: ObR gene expression in cancer cell lines was 50% higher than in the non-cancer cells. Lan-1 and Lan-2 decreased ObR expression in COV434, while it had no effect in KGN cells. Higher ERβ expression in non-cancer and higher ERα expression in both cancer cell lines was noted. SHLA and Lan-1 changed the ratio towards greater expression of ERβ, characteristic of non-cancer granulosa cells. All ObR antagonists in HCrC1 and KGN but only Lan-2 in COV434 reversed leptin-stimulated proliferation. In both non-cancer and cancer granulosa cells, leptin acts as a cyclinD/cdk4, cyclin A/cdk2 and E2F inhibitor.Conclusion: These results indicate that SHLA and Lan2 are promising leptin receptor inhibitors that can eliminate the negative effects of leptin. These compounds should be considered in further ex vivo studies on the cancer microenvironment. [ABSTRACT FROM AUTHOR]

Objective: The role of leptin in mesolimbic signaling of non-food-related rewards has been well established at the preclinical level, yet studies in humans are lacking. The present investigation explored the association between hedonic capacity and leptin dynamics and whether this association differed by BMI class.Methods: In this cross-sectional study of 75 women (42 with BMIs in the lean range and 33 with BMIs in the obesity range), serum leptin before and after meal consumption was measured. Reward capacity was assessed using the Snaith-Hamilton Pleasure Scale (SHAPS). Multiple regression tested whether reward capacity was associated with the leptin area under the curve (AUC), with an interaction term to test differences between the lean and obesity groups.Results: The interaction of SHAPS by BMI group was robust (β = -0.40, P = 0.005); among women with obesity, a greater SHAPS score was associated with a lower leptin AUC (β = -0.35, P = 0.002, adjusted R2  = 0.66). Among those in the lean group, the association was not statistically significant (β = -0.16, P = 0.252, adjusted R2  = 0.22). Findings were above and beyond BMI and age.Conclusions: In this sample, a robust negative association between reward capacity and circulating leptin was stronger in women with obesity compared with lean counterparts. These findings suggest that despite likely leptin resistance, inhibitory leptin functioning related to nonfood rewards may be spared in women with obesity. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is associated with widespread periodontitis and impaired periodontal healing. However, there is a lack of information about the outcomes of regenerative approaches under the influence of osteoporosis. This study investigates the effect of leptin (LEP) overexpression on the regenerative potential of bone marrow stromal cells (BMSCs) in an osteoporotic rat periodontal fenestration defect model.Methods: Rat BMSCs were transfected with adenoviruses harboring the human (h)LEP gene. Cell proliferation and osteogenic differentiation were evaluated. A β-tricalcium phosphate scaffold seeded with transfected cells was implanted into nude mice to investigate ectopic osteogenesis and into an osteoporotic rat defect to study periodontal regeneration. Regenerated periodontal and bone-like tissues were analyzed by histologic methods.Results: hLEP overexpression induced osteogenic differentiation of BMSCs as evidenced by the upregulation of osteogenesis-related genes such as Runt-related transcription factor 2, alkaline phosphatase (ALP), and collagen Type I, as well as increased ALP activity and enhanced mineralization. Mice implanted with hLEP-BMSC-containing scaffolds showed more extensive formation of bone-like tissue than those in other groups. Periodontal defects were also filled to a greater degree when treated with hLEP-BMSCs and contained cementum and a well-organized periodontal ligament after 10 and 28 days.Conclusion: hLEP overexpression in BMSCs can stimulate periodontal regeneration in osteoporotic conditions and might be a promising strategy for periodontal regeneration in patients with osteoporosis. [ABSTRACT FROM AUTHOR]

The satiety inducing hormone leptin acts not only at central nervous system but also at peripheral level. Leptin receptors are found in several sense related organs, including the mouth. A role of leptin in sweet taste response has been suggested but, until now, studies have been based on in vitro experiments, or in assessing the levels of the hormone in circulation. The present study investigated whether the levels of leptin in saliva are related to taste perception in children and whether Body Mass Index (BMI) affects such relationship. Sweet and bitter taste sensitivity was assessed for 121 children aged 9-10 years and unstimulated whole saliva was collected for leptin quantification, using ELISA technique. Children females with lower sweet taste sensitivity presented higher salivary leptin levels, but this is only in the normal weight ones. For bitter taste, association between salivary leptin and caffeine threshold detection was observed only in preobese boys, with higher levels of salivary hormone in low sensitive individuals. This study is the first presenting evidences of a relationship between salivary leptin levels and taste perception, which is sex and BMI dependent. The mode of action of salivary leptin at taste receptor level should be elucidated in future studies. [ABSTRACT FROM AUTHOR]

Background Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented. Two adipokines in particular, leptin and adiponectin, have come to be recognized for their influence on breast cancer risk and tumour biology. Therefore, the aim of this study was to understand the association of differential expression of critical adipokines and associated cellular mechanism in the susceptibility and severity of TNBC in northeast Indian population. Materials and methods We collected 68 TNBC and 63 controls cases and examined for serum leptin and adiponectin levels using enzyme linked immunosorbent assay (ELISA). Leptin Receptor (Ob-R) mRNA expression was determined by real-time polymerase chain reaction (RT-PCR) assay. Differential Ob-R mRNA expression and correlation with cancer stem cell (CSC) markers was evaluated, and correlated with severity. Results The serum leptin levels were significantly associated with TNBC severity, while the adiponectin levels were comparative. The serum leptin levels correlated inversely with the adiponetin levels. Serum leptin levels were unaffected with difference in parity. The difference in leptin levels in pre and post menopausal cases were found to be statistically non-significant. Higher leptin levels were also found to be associated obesity, mortality and recurrence. Obesity was found to be a factor for TNBC pathogenesis and severity. Increased Ob-R mRNA expression was associated with TNBC, significantly with TNBC severity, and was significantly higher in obese patients with higher grade TNBC cases. The Ob-R gene mRNA expression was significantly higher in the obese TNBC cases showing recurrence or mortality. The higher Ob-R gene mRNA expression correlated significantly with higher serum leptin levels and lower serum adiponectin levels in TNBC cases. The Ob-R mRNA expression with associated with modulation of CSC oct4 and nanog . Conclusions In conclusion, the present study is first of its kind on TNBC from northeast India, indicates that adipocytokines does play a role in TNBC pathogenesis. Thus, the understanding of molecular mechanisms of both leptin and adiponectin and their interplay in TNBC offer the prospects for new therapeutic approaches targeting similar signalling pathways. [ABSTRACT FROM AUTHOR]

Protein phosphotyrosine phosphatase 1B (PPTP1B) dephosphorylates receptor and nonreceptor forms of tyrosine kinases, causing the inhibition of their activity and thus regulating appropriate signaling cascades. Increased PPTP1B activity leads to insulin and leptin resistance, being among the causes of type 2 diabetes mellitus and many other metabolic and functional disorders. Selective PPTP1B inhibitors normalize functions of insulin, leptin and some other systems comprising different forms of tyrosine kinases as signaling components, and their development is a promising approach to treat and prevent metabolic disorders. Currently, an active search is in progress for 'binary' PPTP1B inhibitors able to interact simultaneously with the catalytic and allosteric sites of the enzyme, providing thereby high efficiency and selectivity of their action. This review focuses on the status quo of the problem of studying the structure, functions and regulatory properties of PPTP1B, its role in the development of metabolic disorders, as well as on recent advances in designing selective PPTP1B inhibitors. [ABSTRACT FROM AUTHOR]

Leptin is a master regulator of energy balance and body adiposity. Additionally, leptin exerts important control on glucose homeostasis, thermogenesis, autonomic nervous system and neuroendocrine axes. In metabolic diseases, such as obesity and diabetes mellitus, leptin signaling may be compromised, indicating the important role of this hormone in the etiology and pathophysiological manifestations of these conditions. In the present manuscript, we reviewed important concepts of leptin signaling, as well as about the effects of leptin on several biologic functions. We also discussed the possible therapeutic use of leptin administration and how our current obesogenic environment contributes to the development of leptin resistance. Our objective was to provide a comprehensive and state-of-the-art review about the importance of leptin to maintain the homeostasis and during pathological conditions. [ABSTRACT FROM AUTHOR]

Objective: Leptin is an adipocyte-derived hormone and has shown positive correlation with obesity and metabolic syndrome (MetS) in many studies. However, there are few studies investigating this relation in elderly people. Therefore, we aimed to investigate the correlation between the fasting serum leptin level and MetS among older Taiwanese. Materials and Methods: The fasting serum leptin level was obtained from 62 Taiwanese participants over 65 years old and was measured using a commercially available enzyme immunoassay kit. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Results: Thirty elderly participants (48.4%) had MetS. The serum leptin level was positively correlated with MetS (P < 0.001). Multivariate logistic regression analysis of the factors significantly associated with MetS showed that logarithmically transformed leptin (log-leptin, each increase 0.1 ng/mL log-leptin, odds ratio: 1.276, 95% confidence interval: 1.015-1.603, P = 0.037) was still an independent predictor of MetS in elderly persons. Univariable linear analysis showed that body weight (r = 0280, P = 0.028), body mass index (r = 0.417, P = 0.001), waist circumference (r = 0.419, P = 0.001), blood urea nitrogen (r = 0255, P = 0.046), log-insulin (r = 0436, P < 0.001), and logarithmically transformed homeostasis model assessment of insulin resistance (r = 0359, P = 0.004) positively correlated with fasting serum log-leptin levels. Multivariate forward stepwise linear regression analysis of the factors significantly associated with fasting serum log-leptin levels revealed that waist circumference (adjusted R2 = 0.083, P = 0.002), statin use (adjusted R2 = 0.058, P = 0.016), and female gender (adjusted R² = 0.041, P = 0.034) were independent predictors of fasting serum log-leptin levels among elderly participants. Conclusion: In elderly Taiwanese, the serum leptin level was positively correlated with MetS. Waist circumference, statin use, and female gender were independent predictors of the fasting serum leptin level in elderly participants. [ABSTRACT FROM AUTHOR]

Objective: Hypertension is a risk factor for peripheral artery disease (PAD). Serum leptin plays an important role in promoting endothelial dysfunction. The aim of this study is to investigate whether the leptin level is associated with PAD in hypertensive patients. Materials and Methods: Ninety-eight hypertensive patients were enrolled in this study. Ankle-brachial index (ABI) values were measured using an automated oscillometric device. Patients with an ABI value <0.9 were considered the low ABI group. C-reactive protein (CRP) was measured using standard enzymatic automated methods. Serum levels of human leptin were determined using a commercially available enzyme immunoassay. Results: Eighteen (18.4%) hypertensive patients were included in the low ABI group. Hypertensive patients in the low ABI group had higher serum creatinine (P < 0.001), CRP (P = 0.003), and leptin (P < 0.001) levels, higher prevalence of diabetes (P = 0.036), and current smoking (P = 0.034) than patients in the normal ABI group. Univariate linear regression analyses revealed that body weight (P = 0.014), waist circumference (P = 0.010), body mass index (P = 0.002), and logarithmically transformed CRP (log-CRP, P = 0.001) were positively correlated with serum log-leptin levels in hypertensive patients. Multivariate stepwise linear regression analysis showed that log-leptin (β= 0.439, adjusted R² change = 0.224, P < 0.001) was also an associated factor of PAD in hypertensive patients. Conclusion: A higher log-leptin value is an independent predictor of PAD in hypertensive patients. [ABSTRACT FROM AUTHOR]

Leptin, a highly conserved adipocyte-derived hormone, plays important roles in a variety of physiological processes, including the control of fat storage and metabolic status which are linked to food intake, energy homeostasis, and reproduction in all vertebrates. In the present study, we hypothesize that leptin is also present in various organs of the fresh water prawns, Macrobrachium rosenbergii . The existence and distribution of a leptin-like peptide in prawn tissues were verified by using Western blotting (WB) and immunohistochemical detection (ID) using primary antibody against human leptin. With WB, a leptin-like peptide, having a molecular weight of 15 kDa, was detected in the brain, thoracic ganglia, abdominal ganglia, parts of the gastro-intestinal tract, hepatopancreas, adipocytes and gonads. By ID, leptin immunoreactivity (leptin-ir) was detected in the brain, thoracic ganglia and intersegmental commissural nerve fibers of abdominal ganglia. In the gastrointestinal tract, there was intense leptin-ir in the apical part of the epithelial cells of the cardiac and pyloric parts of the stomach. In the midgut and hindgut, the leptin-ir was detected in epithelial cells and basal cells located near the basal lamina of the epithelium. In addition, there was leptin-ir in the Restzellen cells in the hepatopancreas which produce digestive enzymes. In the ovary, the strong intensity of a leptin-ir was detected in the cytoplasm of middle to late stage oocytes, whereas no positive staining was detected in follicular cells. An intense leptin-ir was detected in spermatocytes and sustentacular cells in the seminiferous tubules in the testes of small and orange claw males. Taken together, the detection of the leptin-ir in several organs implicates the existence of a leptin-like peptide in various organs of the freshwater prawn; and like in vertebrates this peptide may be an important hormonal factor in controlling feeding and reproductive process. [ABSTRACT FROM AUTHOR]

A large number of diabetes patients suffer from major depression and are at high risk of mortality. In view of a role of leptin in diabetes, depression and energy homeostasis, the present study concerns circulating levels of leptin in different BMI groups of un-depressed and depressed diabetes patients. Six hundred thirty male and female patients with a primary diagnosis of diabetes were grouped according to BMI and with or without clinical symptoms of depression. Age matched healthy, normal weight male and female volunteers without clinical symptoms of depression or diabetes were taken as controls. Blood samples were obtained after an overnight fast of 12 h. Serum was stored for the determination of leptin and glucose. We found that there were more female than male diabetes patients with comorbid depression. Fasting leptin was higher in normal weight non-diabetes women than men; but comparable in normal weight men and women diabetes patients. Fasting glucose levels were higher in diabetes than non diabetes groups; values were comparable in men and women. Depression was associated with a decrease and increase in leptin respectively in normal-overweight and obese men and women diabetes patients. Glucose levels were also higher in obese depressed than un-depressed diabetes patients. The results suggested that the female gender is at greater risk to comorbid diabetes with depression. Adipo-insular axis plays an important role in diabetes, associated depression and in the greater risk of the female gender to comorbid diabetes with depression. [ABSTRACT FROM AUTHOR]

Leptin, critical in regulation of energy metabolism, is also important for normal bone growth, maturation and turnover. Compared to wild type (WT) mice, bone mass is lower in leptin-deficient ob/ob mice. Osteopenia in growing ob/ob mice is due to decreased bone accrual, and is associated with reduced longitudinal bone growth, impaired cancellous bone maturation and increased marrow adipose tissue (MAT). However, leptin deficiency also results in gonadal dysfunction, disrupting production of gonadal hormones which regulate bone growth and turnover. The present study evaluated the role of increased estrogen in mediating the effects of leptin on bone in ob/ob mice. Three-month-old female ob/ob mice were randomized into one of the 3 groups: (1) ob/ob + vehicle (veh), (2) ob/ob + leptin (leptin) or (3) ob/ob + leptin and the potent estrogen receptor antagonist ICI 182,780 (leptin + ICI). Age-matched WT mice received vehicle. Leptin (40 µg/mouse, daily) and ICI (10 µg/mouse, 2×/week) were administered by subcutaneous injection for 1 month and bone analyzed by X-ray absorptiometry, microcomputed tomography and static and dynamic histomorphometry. Uterine weight did not differ between ob/ob mice and ob/ob mice receiving leptin + ICI, indicating that ICI successfully blocked the uterine response to leptin-induced increases in estrogen levels. Compared to leptin-treated ob/ob mice, ob/ob mice receiving leptin + ICI had lower uterine weight; did not differ in weight loss, MAT or bone formation rate; and had higher longitudinal bone growth rate and cancellous bone volume fraction. We conclude that increased estrogen signaling following leptin treatment is dispensable for the positive actions of leptin on bone and may attenuate leptin-induced bone growth. [ABSTRACT FROM AUTHOR]

Objective, design and methods: Roux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points. Results: After a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (-0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24. Conclusions: Despite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern. [ABSTRACT FROM AUTHOR]

Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance that is often due to unlimited access to food and an increasingly sedentary lifestyle on the background of a genetic and epigenetic vulnerability. Our understanding of the humoral and neuronal systems that mediate the control of energy homeostasis has improved dramatically in the past few decades. However, our ability to develop effective strategies to slow the current epidemic of obesity has been hampered, largely owing to the limited knowledge of the mechanisms underlying resistance to the action of metabolic hormones such as leptin and ghrelin. The development of resistance to leptin and ghrelin, hormones that are crucial for the neuroendocrine control of energy homeostasis, is a hallmark of obesity. Intensive research over the past several years has yielded tremendous progress in our understanding of the cellular pathways that disrupt the action of leptin and ghrelin. In this Review, we discuss the molecular mechanisms underpinning resistance to leptin and ghrelin and how they can be exploited as targets for pharmacological management of obesity. [ABSTRACT FROM AUTHOR]

In addition to its well-known role as an adipostat in adult mammals, leptin has diverse physiological and developmental actions in vertebrates. Leptin has been shown to promote development of hypothalamic circuits and to induce mitosis in different brain areas of mammals. We investigated the ontogeny of leptin mRNA, leptin actions on cell proliferation in the brain, and gene expression in the preoptic area/hypothalamus of tadpoles of Xenopus laevis. The level of leptin mRNA was low in premetamorphic tadpoles, but increased strongly at the beginning of metamorphosis and peaked at metamorphic climax. This increase in leptin mRNA at the onset of metamorphosis correlated with increased cell proliferation in the neurogenic zones of tadpole brain. We found that intracerebroventricular (i.c.v.) injection of recombinant Xenopus leptin (rxLeptin) in premetamorphic tadpoles strongly increased cell proliferation in neurogenic zones throughout the tadpole brain. We conducted gene expression profiling of genes induced at 2 h following i.c.v. injection of rxLeptin. This analysis identified 2,322 genes induced and 1,493 genes repressed by rxLeptin. The most enriched Kyoto Encyclopedia of Genes and Genomes term was the canonical Wnt/β-catenin pathway. Using electroporation-mediated gene transfer into tadpole brain of a reporter vector responsive to the canonical Wnt/β-catenin signaling pathway, we found that i.c.v. rxLeptin injection activated Wnt/β-catenin-dependent transcriptional activity. Our findings show that leptin acts on the premetamorphic tadpole brain to induce cell proliferation, possibly acting via the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background Obesity-related dysregulation of leptin signaling (e.g., hyperleptinemia due to central functional resistance) may affect mood. However, evidence for leptin dysregulation in major depressive disorder (MDD) is conflicting. Inconclusive findings may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the relationship of leptin with MDD, its common subtypes (typical and atypical), and clinical features. Methods The sample consisted of participants (aged 18 to 65 years) from the Netherlands Study of Depression and Anxiety with current ( n = 1062) or remitted ( n = 711) MDD and healthy control subjects ( n = 497). Diagnoses of MDD and subtypes were based on DSM-IV symptoms. Additional symptoms were measured with the Inventory of Depressive Symptomatology. Blood levels of leptin and adiposity indexes (body mass index and waist circumference) were assessed. Results As compared to control subjects, higher leptin was associated with the atypical MDD subtype both for remitted ( n = 144, odds ratio = 1.53, 95% confidence interval = 1.16–2.03, p = .003) and current ( n = 270, odds ratio = 1.90, 95% confidence interval = 1.51–2.93, p = 5.3e-8) cases. This association was stronger for increasing adiposity levels (leptin by body mass index interaction, p < .02), strengthening the hypothesis of the involvement of leptin resistance. No association with leptin was found for overall MDD or the typical subtype. Among currently depressed patients, higher leptin was associated with key symptoms identifying the atypical subtype, such as hyperphagia, increased weight, and leaden paralysis. Conclusions Leptin dysregulation (resistance) may represent an underlying mechanism connecting obesity and MDD with atypical features. Development of treatment effectively targeting leptin resistance may benefit patients with atypical depression characterized by obesity-related metabolic alterations. [ABSTRACT FROM AUTHOR]

Objective: Conflicting results regarding leptin levels in women with polycystic ovary syndrome (PCOS) have been reported. We summarize all available evidence from human participant studies to evaluate leptin levels in PCOS. Data Sources: PubMed, ClinicalTrials.gov, and Web of Science databases were searched with English-language restriction for only human beings from the inception to December 31, 2015. Search terms included PCOS (polycystic ovary syndrome or PCOS) and leptin. Methods of Study Selection: A total of 238 studies were reviewed, and a total of 19 studies, involving 991 women with PCOS and 898 controls, were eligible for our meta-analysis. Studies were eligible if provided leptin means and standard deviation in women with PCOS and healthy women controls. Results: Parameters, such as body mass index, insulin resistance (IR), and total testosterone, which may influence leptin levels were extracted. Data were collected and analyzed by RevMan 5.3 and Stata/SE14.0. The pooling analysis of all relevant studies revealed that leptin levels were significantly higher in patients with PCOS than in controls, with standardized mean difference of 1.62 (95% confidence interval: 1.01-2.23). However, the heterogeneity across studies was considerable and not eliminated in subgroup analyses. Meta-regression analysis further suggested that the heterogeneity might be relevant to variability in IR and study location. Conclusion: Elevated leptin levels are detected in women with PCOS compared with non-PCOS controls. Higher leptin levels may be correlated with IR, metabolic disorder, infertility, and even cardiovascular disease risk in PCOS, which may contribute to the etiology and development of PCOS. [ABSTRACT FROM AUTHOR]