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Sample records for higher leptin levels

  1. Correlation of leptin and soluble leptin receptor levels with anthropometric parameters in mother-newborn pairs

    PubMed Central

    Marino-Ortega, Linda A; Molina-Bello, Adiel; Polanco-García, Julio C; Muñoz-Valle, José F; Salgado-Bernabé, Aralia B; Guzmán-Guzmán, Iris P; Parra-Rojas, Isela

    2015-01-01

    The aim of this study was to investigate if anthropometric parameters are associated with both leptin and soluble leptin receptor (sLEPR) levels in newborns and their mothers. This cross-sectional study was performed in 118 mother-newborn pairs. The venous blood sample of mothers was taken before delivery and immediately after delivery an umbilical cord blood sample was collected. Levels of leptin and sLEPR in maternal and umbilical cord sera were assessed by ELISA. Maternal serum concentration of leptin and sLEPR (6.2 and 25.7 ng/ml, respectively) were higher than in umbilical cord blood (2.4 and 14.2 ng/ml, respectively). However, the newborns and their mothers had higher sLEPR levels than leptin levels. In mothers was observed that leptin levels increase with weight gain in pregnancy and decreased sLEPR levels. Cord leptin levels correlated with neonatal birth weight and length, the body circumferences, placental weight and maternal leptin levels. Cord sLEPR levels correlated with maternal sLEPR and leptin levels. Maternal serum concentration of leptin correlated with pre-pregnancy BMI, weight gain, cord sLEPR and leptin levels. Maternal sLEPR concentration correlated with cord sLEPR levels. The leptin and sLEPR levels in mother-newborn pairs are related with anthropometric parameters and an inverse correlation between leptin levels and sLEPR was observed in pairs. PMID:26379933

  2. A high sugar, low fiber meal leads to higher leptin and physical activity levels in overweight Latina females as opposed to a low sugar, high fiber meal

    PubMed Central

    Belcher, Britni; Anderson, David; Lane, Christianne Joy; Chou, Chih-Ping; Salter-Venzon, Dawna; Davis, Jaimie N.; Janice Hsu, Ya-Wen; Neuhouser, Marian L.; Richey, Joyce M.; McKenzie, Thomas L; McClain, Arianna; Goran, Michael I; Weigensberg, Marc J

    2009-01-01

    Acute effects of high sugar, low fiber meals (HS) versus low sugar, high fiber meals (LS) on hormones and behavior were studied in 10 overweight Latina females, age 11-12, using a crossover design. In this exploratory pilot study, articipants arrived fasted at an observation laboratory on two occasions, and randomly received either a HS meal or a LS meal at each visit. Glucose, insulin, and leptin were assayed from serum drawn at 0, 15, 30, 60, 90 and 120 minutes. Ad-libitum snacks were provided at 120 minutes. Physical activity was measured using an observational system that provides data on time spent lying down, sitting, standing, walking, and in vigorous activity. Data was collected between March, 2005 and July, 2006. In the HS condition, glucose and leptin levels decreased more slowly, glucose levels were higher at 60 minutes (111.2 mg/dl vs 95.4 mg/dl, P = .03), leptin levels were higher at 90 minutes (49.3 vs 46.7 ng/ml, P = .017) than in the LS condition. Meals did not effect insulin or ad-libitum dietary intake. Sitting, standing, lying down and vigorous activity differed by condition, but not walking. Participants were significantly more active in the first 30-60 post-HS minutes, but after 60 minutes there was a trend for activity to be lower after the HS meal vs. the LS meal. High sugar meals sustain glucose and leptin levels longer, which may play an important role in modulating levels of physical activity in this group at high risk of obesity-related disease. PMID:19465188

  3. Leptin levels in the obese African parturient.

    PubMed

    Kafulafula, G; Moodley, J

    2001-05-01

    Prolactin, HCG and oestrogen are reported to have a role in regulating serum leptin levels and therefore adiposity in pregnancy. The aim of this study was to determine serum leptin levels during pregnancy in African women, and was conducted in the Antenatal Clinic, King Edward VIII Hospital, Durban, South Africa. Eighty-two obese and non-obese women were studied. Demographic details and anthropometric measurements were recorded, and serum leptin levels determined by radio-immunoassay in all women. Age, parity and gestational age showed a weak correlation with leptin levels. Weight (4=0.6); body mass index (r=0.5), and the circumference of midarm (r=0.4), waist (4-0.6, hip (5=0.5) and thigh correlated positively with leptin values. Serum leptin values in African pregnant women are not dissimilar to that of studies in other racial groups. PMID:12521847

  4. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

    PubMed

    Isidori, A M; Caprio, M; Strollo, F; Moretti, C; Frajese, G; Isidori, A; Fabbri, A

    1999-10-01

    Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced

  5. Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestational diabetes mellitus in Chinese population

    PubMed Central

    Yang, Mei; Peng, Songxu; Li, Wei; Wan, Zhihua; Fan, Linlin; Du, Yukai

    2016-01-01

    The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time polymerase chain reaction assay. The results showed that plasma leptin levels were significantly higher in the impaired fasting glucose (IFG) group than NGT group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05). Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant body mass index, homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index both in GDM and NGT group (P < 0.05). However, neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high leptin level was associated with GDM. And larger and more rigorous researches were needed to further explore the association of LEP and LEPR gene polymorphisms and GDM among Chinese population. PMID:27034205

  6. Study of Serum Levels of Leptin, C-Reactive Protein and Nutritional Status in Hemodialysis Patients

    PubMed Central

    Montazerifar, Farzaneh; Karajibani, Mansour; Hassanpour, Zahra; Pourmofatteh, Mahla

    2015-01-01

    Background: Leptin is secreted by adipose tissue and decreases appetite. However, the role of leptin in the pathogenesis of hemodialysis (HD)-related malnutrition has not been fully evaluated. Objectives: The aim of study was to investigate the association between the serum leptin levels, serum C-reactive protein (CRP) levels, and nutritional status in hemodialysis patients. Patients and Methods: This analytical descriptive study included 45 hemodialysis patients and 40 healthy subjects. Biochemical parameters and serum leptin levels were measured. The nutritional status was evaluated using a food frequency questionnaire (FFQ) and the calculation of the body mass index (BMI). Results: Serum leptin (P < 0.05) and albumin (P < 0.0001) levels and BMI (P < 0.001) of HD patients were significantly lower, while CRP levels were significantly higher than those of controls (P < 0.0001). HD patients consumed the lower daily servings of the food groups compared to the control subjects (P < 0.0001). A significant positive correlation between serum levels of leptin and albumin and BMI was demonstrated. No significant correlations were identified between leptin level, CRP level, and other variables. Conclusions: The findings suggest that low levels of leptin may be a contributory factor for malnutrition in HD patients. Further studies are required to ascertain the significance of leptin levels in relation to nutritional factors in hemodialysis patients. PMID:26430525

  7. Leptin, adiponectin and serotonin levels in lean and obese dogs

    PubMed Central

    2014-01-01

    Background Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Results Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). Conclusions 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity. PMID:24886049

  8. Genetic variants in leptin: Determinants of obesity and leptin levels in South Indian population

    PubMed Central

    Dasgupta, Shruti; Salman, Mohammed; Siddalingaiah, Lokesh B; Lakshmi, GL; Xaviour, D; Sreenath, Jwalapuram

    2014-01-01

    The revelation of leptin action mechanisms has led to various attempts to establish the association of polymorphisms in the leptin gene with obesity-related phenotypes. But, outcomes have been contradicting, which made the information on the role of the leptin gene in regulating the mechanism of pathophysiology of obesity inexplicable. Moreover, none of the studies are known to have similar implications on the Indian population. To address such contradictions, our study aims to evaluate the association of leptin gene polymorphism with obesity and leptin levels in a South Indian Population. A total of 304 cases (BMI≥27.5) and 309 controls (BMI≤23) from local inhabitants of Mysore, Karnataka were recruited for the study. The leptin gene variants rs7799039, rs2167270 and rs4731426 independently, as well as in 4 haplotype combinations, were found to be significantly associated with the risk of obesity. An increasing trend in BMI and leptin levels was observed with every addition of A and C minor alleles of exonic variant (rs2167270) and intronic variant (rs4731426) respectively. However, only AA genotype of SNP rs7799039 was positively associated with BMI. None of the SNPs were associated with fat percentage and waist to hip ratio. On a whole, this data suggests that the common polymorphisms in the leptin gene are strong predictors of obesity and leptin levels in South Indians. PMID:26167411

  9. Sperm motility inversely correlates with seminal leptin levels in idiopathic asthenozoospermia

    PubMed Central

    Guo, Jianhua; Zhao, Yang; Huang, Weiying; Hu, Wei; Gu, Jianjun; Chen, Chuhong; Zhou, Juan; Peng, Yubing; Gong, Min; Wang, Zhong

    2014-01-01

    Background: Asthenozoospermia is one kind cause of male infertility. Nevertheless, no specific etiology can be identified by routine tests in some cases. Recently, it has been shown that leptin plays a critical role in male fertility. However, the link between leptin and sperm motility is yet to be determined. The aim of this study was to explore association between seminal and serum leptin levels and sperm motility in idiopathic asthenozoospermia. Methods: Our study included 79 asthenozoospermic men and 77 normozoospermic men. Semen was assessed by volume, sperm concentration, motility and morphology. Serum gonadotropic and sex hormones were determined by a chemiluminescent assay. The leptin levels in serum and seminal plasma were detected with ELISA. Results: The mean seminal leptin level in asthenozoospermic group was significantly higher than that in control group, but there was no significant difference in the serum leptin levels between these two groups. The serum leptin had no significant correlation with sperm motility. The seminal leptin had significantly negative correlation with sperm progressive motility and serum total testosterone. Conclusions: The findings indicate a pathophysiological relevance of seminal leptin in sperm motility. PMID:25419396

  10. Effects of nutritional status on plasma leptin levels and in vitro regulation of adipocyte leptin expression and secretion in rainbow trout.

    PubMed

    Salmerón, Cristina; Johansson, Marcus; Angotzi, Anna R; Rønnestad, Ivar; Jönsson, Elisabeth; Björnsson, Björn Thrandur; Gutiérrez, Joaquim; Navarro, Isabel; Capilla, Encarnación

    2015-01-01

    As leptin has a key role on appetite, knowledge about leptin regulation is important in order to understand the control of energy balance. We aimed to explore the modulatory effects of adiposity on plasma leptin levels in vivo and the role of potential regulators on leptin expression and secretion in rainbow trout adipocytes in vitro. Fish were fed a regular diet twice daily ad libitum or a high-energy diet once daily at two ration levels; satiation (SA group) or restricted (RE group) to 25% of satiation, for 8weeks. RE fish had significantly reduced growth (p<0.001) and adipose tissue weight (p<0.001), and higher plasma leptin levels (p=0.022) compared with SA fish. Moreover, plasma leptin levels negatively correlated with mesenteric fat index (p=0.009). Adipocytes isolated from the different fish were treated with insulin, ghrelin, leucine, eicosapentaenoic acid or left untreated (control). In adipocytes from fish fed regular diet, insulin and ghrelin increased leptin secretion dose-dependently (p=0.002; p=0.033, respectively). Leptin secretion in control adipocytes was significantly higher in RE than in SA fish (p=0.022) in agreement with the in vivo findings, indicating that adipose tissue may contribute to the circulating leptin levels. No treatment effects were observed in adipocytes from the high-energy diet groups, neither in leptin expression nor secretion, except that leptin secretion was significantly reduced by leucine in RE fish adipocytes (p=0.025). Overall, these data show that the regulation of leptin in rainbow trout adipocytes by hormones and nutrients seems to be on secretion, rather than at the transcriptional level. PMID:25448259

  11. Association between Follicular Fluid Leptin and Serum Insulin Levels in Nonoverweight Women with Polycystic Ovary Syndrome

    PubMed Central

    Garruti, G.; de Palo, R.; Rotelli, M. T.; Nocera, S.; Totaro, I.; Nardelli, C.; Panzarino, M. A.; Vacca, M.; Selvaggi, L. E.; Giorgino, F.

    2014-01-01

    Aims. We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW) women with PCOS (NOW-PCOS) from Apulia undergoing in vitro fertilization/embryo transfer (IVF). Materials and Methodology. We recruited 16 NOW women with PCOS (NOW-PCOS) and 10 normally ovulating NOW women (control-NOW). All women underwent IVF. Androgens, 17-β-estradiol (17β-E2), and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin). Results. In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. Conclusions. Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance. PMID:24895638

  12. Effect of Obesity and Leptin Level on Migraineurs

    PubMed Central

    Ligong, Zhang; Jinjin, Qin; Chunfu, Chen; Congcong, Li; Xiaojun, Diao

    2015-01-01

    Background The aim of this study was to analyze the effects of obesity and leptin levels on patients with migraine, and to observe the change of leptin levels in migraineurs. Material/Methods We enrolled 52 migraine patients from the Headache Clinic in Shandong Provincial Hospital into a randomized controlled trial with another 52 age-, sex-, and BMI-matched healthy subjects as controls. Leptin levels in all subjects were determined by radioimmunoassay. Results Compared with the control group, the migraineurs revealed no significant change in leptin levels (P>0.05). Multivariate Logistic regression analysis showed that neither abdominal obesity nor leptin had significant impact on migraine clinical features. Total body obesity had a significant effect on the frequency (OR=4.248), duration (OR=3.167), and intensity (OR=5.225) of the headache. Conclusions Total body obesity affected headache frequency, intensity, and duration, while leptin levels did not. PMID:26508370

  13. Clinical aspects of leptin.

    PubMed

    Sinha, M K; Caro, J F

    1998-01-01

    Hyperleptinemia is an essential feature of human obesity. Total body fat mass > % body fat > BMI are the best predictors of circulating leptin levels. Although ob gene is differentially expressed in different fat compartments, apart from total body fat, upper or lower body adiposity or visceral fat does not influence basal leptin levels. Similarly, age, basal glucose levels, and ethnicity do not influence circulating leptin levels. Only in insulin-sensitive individuals do basal levels of insulin and leptin correlate positively even after factoring in body fat. Diabetes does not influence leptin secretion in both lean and obese subjects per se. Independent of adiposity, leptin levels are higher in women than in men. This sexual dimorphism is also present in adolescent children. In eating disorders anorexia nervosa and bulimea nervosa, leptin levels are not upregulated but simply reflect BMI and probably body fat. In spite of strong correlation between body fat and leptin levels, there is great heterogeneity in leptin levels at any given index of body fat. About 5% of obese populations can be regarded as "relatively" leptin deficient which could benefit from leptin therapy. Leptin has dual regulation in human physiology. During the periods of weight maintenance, when energy intake and energy output are equal, leptin levels reflect total bodyfat mass. However, in conditions of negative (weight-loss programs) and positive (weight-gain programs) energy balances, the changes in leptin levels function as a sensor of energy imbalance. This latter phenomenon is best illustrated by short-term fasting and overfeeding experiments. Within 24 h of fasting leptin levels decline to approximately 30% of initial basal values. Massive overfeeding over a 12-h period increases leptin levels by approximately 50% of initial basal values. Meal ingestion does not acutely regulate serum leptin levels. A few studies have shown a modest increase in leptin secretion at supraphysiological

  14. [Impact of leptin levels on outcome of in vitro fertilization-embryo transfer

    PubMed

    Yang, Xiao-Fu; Huang, He-Feng

    2002-06-01

    OBJECTIVE: To investigate the impact of ovarian stimulation on leptin levels and their effect on in vitro fertilization-embryo transfer (IVF-ET). METHODS: In 39 women who underwent IVF-ET, serum and follicular fluid leptin and E(2) levels were measured by enzyme-linked immunosorbent assay and radioimmunoassay. Blood samples were collected just prior to FSH and HCG injection and follicles puncture. Follicular fluid was collected at the time of oocyte retrieval. RESULTS: The serum leptin levels before HCG administration (26.1+/-2.3)&mgr;g/L were significantly higher than before FSH administration (9.3+/-1.0)&mgr;g/L and oocyte retrieval (15.8+/-2.3)&mgr;g/L(P<0.001). On the day of oocyte retrieval, there was no significant difference between the serum leptin(15.8+/-2.3)&mgr;g/L.and the follicular fluid leptin (18.5+/-2.2)&mgr;g/L. Serum and follicular leptin levels in successful pregnancies were significantly lower(P<0.05) than in women with failed conception. CONCLUSION: It could indicate that high leptin levels may interfere with the developing of dominant follicles. PMID:12596302

  15. Association between Plasma Leptin Level and Systemic Inflammatory Markers in Patients with Aggressive Periodontitis

    PubMed Central

    Shi, Dong; Liu, Yun-Yu; Li, Wei; Zhang, Xin; Sun, Xiao-Jun; Xu, Li; Zhang, Li; Chen, Zhi-Bin; Meng, Huan-Xin

    2015-01-01

    Background: Increasing evidence supports an association between periodontitis and systemic diseases. Leptin is involved both in the energy metabolism and inflammatory processes and is suggested to be a link between periodontal infection and systemic health. The present study aimed to evaluate the peripheral leptin concentration in patients with aggressive periodontitis (AgP) and to explore the relationship between leptin and systemic inflammation. Methods: Ninety patients with AgP visiting the Clinic of the Periodontology Department, Peking University School and Hospital of Stomatology between July 2001 and May 2006, and 44 healthy controls (staff and student volunteers in the same institute) were recruited. Plasma levels of leptin and inflammatory cytokines including interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by enzyme-linked immunosorbent assay. Correlation and multiple linear regression analysis were performed to analyze the association between plasma leptin level and other variables. Results: Plasma leptin level of AgP group was significantly higher than that of the control group (19.7 ± 4.4 ng/ml vs. 7.5 ± 1.3 ng/ml, P < 0.01). After controlling for age, gender, and body mass index, positive correlation was observed between plasma leptin concentration and log-transformed levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and CRP), and the partial correlation coefficients ranged from 0.199 to 0.376 (P < 0.05). Log-transformed IL-1β and IL-6 levels entered the final regression model (standardized β were 0.422 and 0.461 respectively, P < 0.01). Conclusions: Elevated plasma leptin concentration may be associated with increased systemic levels of inflammatory markers in AgP patients. PMID:25673458

  16. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels

    PubMed Central

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A.; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H.; Hamilton, Steven P.; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G.; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-01-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 × 10−5) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  17. Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.

    PubMed

    Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H; Hamilton, Steven P; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marcus; Uhr, Manfred; Dose, Tatjana; Unschuld, Paul G; Zihl, Josef; Binder, Elisabeth; Müller-Myhsok, Bertram; Holsboer, Florian; Lucae, Susanne

    2013-07-01

    Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(⁎)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant

  18. Elevated Serum Leptin Levels are Associated With an Increased Risk of Sentinel Lymph Node Metastasis in Cutaneous Melanoma

    PubMed Central

    Oba, Junna; Wei, Wei; Gershenwald, Jeffrey E.; Johnson, Marcella M.; Wyatt, Cynthia M.; Ellerhorst, Julie A.; Grimm, Elizabeth A.

    2016-01-01

    Abstract The metabolic hormone leptin has been implicated in the pathogenesis of various malignancies and may contribute to the high rate of cancer in obese individuals. We reported that leptin and its receptor are expressed by melanoma tumors and cell lines, and that leptin stimulates proliferation of cultured melanoma cells. Here, we tested the hypothesis that leptin contributes to early melanoma progression by assessing its association with sentinel node positivity in cutaneous melanoma patients. The study enrolled 72 patients who were scheduled to undergo lymphatic mapping and sentinel node biopsy. Fasting blood was obtained before surgery, and serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA) with a “raw” (assay value) and an “adjusted” value (raw value divided by body mass index). Leptin levels and other clinicopathologic parameters were compared between sentinel node positive and negative groups. Logistic regression models were used to predict sentinel node status using leptin and other relevant clinical parameters. The raw and adjusted leptin levels were significantly higher in the 15 patients with positive sentinel nodes. These findings could not be attributed to differences in body mass indices. Univariate models revealed raw leptin, adjusted leptin, Breslow thickness, and mitotic rate as significant predictors of sentinel node status. Leptin levels and Breslow thickness remained significant in multivariate models. Survival and follow-up analysis revealed more aggressive disease in diabetic patients. Elevated serum leptin levels predict sentinel node metastasis in melanoma. Validation of this finding in larger cohorts should enable better stratification of early stage melanoma patients. PMID:26986135

  19. The severity of liver fibrosis is associated with high leptin levels in chronic hepatitis C.

    PubMed

    Piche, T; Vandenbos, F; Abakar-Mahamat, A; Vanbiervliet, G; Barjoan, E M; Calle, G; Giudicelli, J; Ferrua, B; Laffont, C; Benzaken, S; Tran, A

    2004-01-01

    Recent attention has focused on the liver profibrogenic role of leptin in animal models. The purpose of this study was to evaluate the role of leptin and TNF-alpha in the severity of liver fibrosis in patients with chronic hepatitis C (CHC). We used a radioimmunoassay to determine serum leptin concentrations in 77 consecutive patients with CHC and 22 healthy controls. Leptin was correlated with liver histological (METAVIR) and metabolic indices. Sixty five patients had none to moderate liver fibrosis (F0-F2) and twelve severe fibrosis (F3-F4). Steatosis was observed in all but 27 patients. Leptin was significantly increased in patients compared with controls and was significantly more elevated in females both in patients and controls. The age, age at infection, prothrombin index, body mass index (BMI), triglycerides, glycaemia, ferritin, leptin and TNF-alpha, were associated with severe fibrosis. Steatosis was significantly more pronounced in patients with severe than those without or moderate fibrosis (P = 0.04). Only leptin was significantly and independently associated with severe fibrosis (OR = 1.2, CI 95%: 1.1-1.4, P = 0.03). Leptin was significantly associated with BMI (r = 0.64, P < 0.001) and glycaemia (r = 0.43, P < 0.001). Significant correlations were found between steatosis and BMI (r = 0.30, P < 0.01) and glycaemia (r = 0.30, P < 0.01). In patients with CHC and higher BMI and glycaemia levels, the severity of liver fibrosis is associated with serum leptin. TNF-alpha is a putative candidate involved in the mechanism. PMID:14738564

  20. Association of Serum Leptin Level with Obesity in Children with Acute Lymphoblastic Leukemia

    PubMed Central

    Zareifar, S; Shorafa, S; Haghpanah, S; Karamizadeh, Z; Adelian, R

    2015-01-01

    Background Obesity is a medical problem in survivors of childhood acute lymphoblastic leukemia. Obesity is associated with many complications, so it is important to investigate the respective etiology. Leptin is a protein synthesized in the fatty tissue and is effective in the control of obesity. Survey of leptin in acute lymphoblastic leukemia (ALL) survivors could be helpful in controlling obesity. Materials and Methods In this prospective study, 53 pediatric patients diagnosed with ALL between 2006 and 2012 from Southern Iran, were enrolled. We examined body mass index (BMI) status and performed laboratory measuring tests including triglyceride, cholesterol, fasting blood sugar, leptin at diagnosis time and then every 6 months and in the last visit. Results Participants consisted of 35 male and 18 female patients. At the time of diagnosis, 5.66% were overweight or obese, whereas at the end of treatment, approximately 13 patients (24.53%) were overweight or obese. The median and interquartile range (IQR) for blood leptin level were significantly higher for obese patients than other patients (885, 1120 vs. 246, 494 pg/ml), (P=0.030). The median and IQR were also significantly higher in females than in males (861, 969 vs. 204, 267 pg/ml), (P=0.006). Conclusion Obesity is a complication of ALL treatment. It is associated with elevated blood leptin level. Hypothalamus leptin resistance in obese patients should be considered. In each visit, clinicians should weight and their patient’s BMI take into account. PMID:26705449

  1. Short-term human chorionic gonadotropin-induced testosterone rise does not modify leptin levels in eugonadal men.

    PubMed

    Panidis, D; Koliakos, G; Kourtis, A; Rousso, D; Mavromatidis, G; Triantos, A; Kalahanis, I

    2002-02-01

    The aim of this study was to monitor serum leptin concentrations after altering the levels of testosterone, by intramuscular administration of human chorionic gonadotropin (hCG), in eugonadal men. A 7-day monitoring of hCG, testosterone and leptin levels was performed after intramuscular administration of a dose of 5000 IU hCG in these men. Thirty fertile men aged 23-38 years were studied. In addition, 30 women aged 18-34 years with normal ovulatory cycles were studied, to verify reports of sexual dimorphism in serum leptin levels. These 60 individuals were divided into four groups, according to their sex and body mass index (BMI) values. In men, blood samples were collected at 09.00, after an overnight fast, for the determination of hCG, testosterone and leptin levels, and, immediately thereafter, a dose of 5000 IU hCG was administered intramuscularly. Further blood samples were collected at 24-h intervals for a period of 7 days for determination of the same hormones. In women, blood samples were collected only once, at 09.00, after an overnight fast between the 3rd and the 6th day of the menstrual cycle, for determination of serum estradiol and leptin levels. Our results showed that the mean value of leptin in thin men and women was significantly lower than that in obese men and women, respectively. The mean value of leptin in thin women was significantly higher than that in obese men. Serum leptin concentrations decreased significantly, 168 h after short-term hCG administration. There was a significant positive correlation between BMI values and serum leptin concentrations, in both men and women. Our results support the view that hCG administration in eugonadal men does not influence serum leptin levels. Moreover, a short-term increase of serum testosterone levels, after one dose of hCG, is not sufficient to affect and modify leptin secretion mechanisms in vivo. PMID:11915586

  2. Leptin receptor gene expression and number in the brain are regulated by leptin level and nutritional status.

    PubMed

    Mitchell, Sharon E; Nogueiras, Ruben; Morris, Amanda; Tovar, Sulay; Grant, Christine; Cruickshank, Morven; Rayner, D Vernon; Dieguez, Carlos; Williams, Lynda M

    2009-07-15

    Hormone potency depends on receptor availability, regulated via gene expression and receptor trafficking. To ascertain how central leptin receptors are regulated, the effects of leptin challenge, high-fat diet, fasting and refeeding were measured on leptin receptor number and gene expression. These were measured using quantitative (125)I-labelled leptin in vitro autoradiography and in situ hybridisation, respectively. Ob-R (all forms of leptin receptor) expression in the choroid plexus (CP) was unchanged by high-fat diet or leptin challenge, whereas fasting increased but refeeding failed to decrease expression. (125)I-labelled leptin binding to the CP was increased by fasting and returned to basal levels on refeeding. (125)I-Labelled leptin was reduced by leptin challenge and increased by high-fat feeding. Ob-Rb (signalling form) in the arcuate (ARC) and ventromedial (VMH) nuclei was increased after fasting and decreased by refeeding. Leptin challenge increased Ob-Rb expression in the ARC, but not after high-fat feeding. In general, changes in gene expression in the ARC and VMH appeared to be largely due to changes in area rather than density of labelling, indicating that the number of cells expressing Ob-Rb was the parameter that contributed most to these changes. Leptin stimulation of suppressor of cytokine signalling 3 (SOCS3), a marker of stimulation of the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway, was unchanged after high-fat diet. Thus, early loss of leptin sensitivity after high-fat feeding is unrelated to down-regulation of leptin receptor expression or number and does not involve the JAK/STAT pathway. The effect of leptin to decrease (125)I-labelled leptin binding and the loss of ability of leptin to up-regulate Ob-Rb expression in the ARC after high-fat feeding offer potential mechanisms for the development of leptin insensitivity in response to both hyperleptinaemia and high-fat diet. PMID:19491239

  3. Circulating leptin and osteoprotegerin levels affect insulin resistance in healthy premenopausal obese women.

    PubMed

    Ugur-Altun, Betul; Altun, Armagan

    2007-11-01

    We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women. PMID:17923273

  4. No alteration in serum leptin levels during acute endotoxemia in sheep.

    PubMed

    Soliman, M; Abdelhady, S; Fattouh, I; Ishioka, K; Kitamura, H; Kimura, K; Saito, M

    2001-10-01

    To determine the role of leptin in endotoxin-induced anorexia in ruminants, circulating leptin levels were measured during acute experimental endotoxemia in sheep. Injection of bacterial lipopolysaccharide (450 ng/kg, i.v.) induced anorexia accompanied with fever and increases in serum levels of cortisol, insulin and glucose which are known to stimulate leptin secretion in rodent and human, while it did not affect serum leptin levels at all. These results indicate that serum leptin levels in sheep during acute endotoxemia are differentially regulated from those in rodent and human, and that leptin might not be involved in the endotoxin-induced anorexia in sheep. PMID:11714034

  5. Plasma Leptin levels, LEPR Q223R Polymorphism and Mammographic Breast Density: a cross-sectional study

    PubMed Central

    Dallal, Cher; Garte, Seymour; Ragin, Camille; Chen, Jiangying; Lloyd, Stacy; Modugno, Francesmary; Weissfeld, Joel; Taioli, Emanuela

    2015-01-01

    Obesity is associated with breast cancer in post-menopausal women, and breast density is a marker of breast cancer risk. Leptin is produced by the adipose tissue, acts through receptors that are polymorphic in nature, and is considered a cancer growth factor. The relationship between Body Mass Index, leptin, leptin receptors and breast density is not well studied. A cross-sectional analysis in 392 post-menopausal healthy women was conducted; participants provided permission to obtain copies of their most recent screening mammogram. Nonfasting plasma leptin levels were determined using a commercially available leptin ELISA kit. The Q223R genotypes of the LEPR gene were performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis using DNA extracted from buffy coat samples. A statistically significant positive relationship was observed between leptin levels and body mass index (P value<0.0001); leptin was significantly positively associated with mammography total breast area and non-dense breast area (P-value<0.0001), while was significantly inversely associated with percent breast density (P-value<0.0001). Leptin levels varied across the LEPR Q223R polymorphism, and were higher in women homozygous for the AA variant. Percent breast density decreased across the LEPR Q223R genotype, with lower percent density in women with the AA genotype. When dense area was considered for quartiles of leptin by LEPR Q223R, a significant inverse trend between leptin levels and dense breast area was observed only among women with the G/G genotype (P-trend<0.001). After adjustment for possible confounders, leptin levels were significantly inversely associated with percent breast density (p=0.01). A significant interaction between body mass index and leptin levels on percent breast density was observed (p=0.03). These findings suggest that the association between leptin and breast density may vary by LEPR Q223R genotype, and that body mass index

  6. Effects of gonadotropin and testosterone treatments on plasma leptin levels in male patients with idiopathic hypogonadotropic hypogonadism and Klinefelter's syndrome.

    PubMed

    Ozata, M; Ozisik, G; Caglayan, S; Yesilova, Z; Bingöl, N; Saglam, M; Turan, M; Beyhan, Z

    1998-05-01

    Since little is known about the effects of gonadotropin and testosterone treatment on leptin levels in male hypogonadism, we determined fasting plasma leptin levels before and 3 months after treatment in 21 patients with idiopathic hypogonadotropic hypogonadism (IHH), 16 patients with Klinefelter's syndrome and 20 male controls. Patients with IHH were treated with hCG/human menopausal gonadotropin, whereas patients with Klinefelter's syndrome received T treatment. Plasma leptin levels were measured by an RIA with a sensitivity of 0.5 microg/L. Mean leptin levels in patients with IHH before treatment (9.23+/-4.09 microg/L) were not significantly different from those in patients with Klinefelter's syndrome (7.29+/-5.05 microg/L; z=-1.41; P=0.15). Leptin levels in both IHH and Klinefelter's syndrome groups were, however, significantly higher than in the normal men (3.91+/-1.67 microg/L) (P<0.001 and P<0.01, respectively). Mean leptin levels did not change significantly 3 months after the initiation of gonadotropin (11.6+/-6.44 microg/L) or T (8.32+/-5.17 microg/L) treatment in either IHH or Klinefelter's syndrome. Our study demonstrated that mean plasma leptin levels are not influenced by short-term gonadotropin or T treatment in male hypogonadism. PMID:9660087

  7. Higher white adipocyte area and lower leptin production in adult rats overfed during lactation.

    PubMed

    Conceição, E P S; Trevenzoli, I H; Oliveira, E; Franco, J G; Carlos, A S; Nascimento-Saba, C C A; Moura, E G; Lisboa, P C

    2011-06-01

    Litter size reduction during lactation is a good model for childhood obesity since it induces overnutrition and programming for obesity at adulthood. Adult offspring develop higher fat mass content, hyperinsulinemia and insulin resistance, hypertension, lower HDL cholesterol, hyperphagia, and leptin resistance. Leptin resistance is often associated with hyperleptinemia. Although we observed higher SOCS3 and lower STAT3 in the hypothalamus of rats raised in small litters featuring a central leptin resistance, they showed unexpected normoleptinemia at 180 days old. Then, to clarify why early overfed rats did not develop hyperleptinemia when adult, we studied the leptin production by the visceral and subcutaneous adipose tissue and skeletal muscle as well as the morphology in the 2 different fat depots. To induce EO, litter size was reduced to 3 pups/litter (SL group) on the 3 (rd) day of life. In controls (NL group), litter size was adjusted to 10 pups/litter. Rats were killed at 180 days old. The programming of adipose tissue morphology by early overnutrition is specific between the different fat depots with hypertrophy only in the visceral compartment. In addition, the visceral adipocyte showed lower leptin content that may indicate a reduced leptin synthesis. These data suggest that adipocytes from SL rats are dysfunctional, since a higher leptin production in larger adipose cells is expected. In conclusion, postnatal nutrition is determinant for future leptin production by different fat depots as well as adipocyte morphology. These changes seem to be related to the severity of obesity and its metabolic consequences. PMID:21512961

  8. The Impact of LEP G-2548A and LEPR Gln223Arg Polymorphisms on Adiposity, Leptin, and Leptin-Receptor Serum Levels in a Mexican Mestizo Population

    PubMed Central

    Chavarria-Avila, Efraín; Gomez-Bañuelos, Eduardo; Ruiz-Quezada, Sandra-Luz; Castro-Albarran, Jorge; Sánchez-López, Lizeth; Martín-Marquez, Beatriz Teresita; Navarro-Hernández, Rosa-Elena

    2015-01-01

    The polymorphisms in leptin (LEP G-2548A) and leptin-receptor (LEPR Gln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2 ± 31.35 ng/mL) but lower sLeptin-receptor (12.6 ± 3.74 ng/mL) levels than normal weight ones (17.6 ± 14.62 ng/mL, 17.4 ± 4.62 ng/mL, resp.), P < 0.001. Obese subjects carriers of Arg/Arg genotype had more (P = 0.016) sLeptin-receptor (14.7 ± 4.96 ng/mL) and less (P = 0.004) sLeptin (44.0 ± 28.12 ng/mL) levels than Gln/Gln genotype (11.0 ± 2.92 ng/mL, 80.3 ± 33.24 ng/mL, resp.). Body fat mass was lower (P from 0.003 to 0.045) for A/A (36.5% ± 6.80) or Arg/Arg (36.8% ± 6.82) genotypes with respect to G/G (41.3% ± 5.52) and G/A (41.6% ± 5.61) or Gln/Gln (43.7% ± 4.74) and Gln/Arg (41.0% ± 5.52) genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico. PMID:26064921

  9. Leptin Level and Skipping Breakfast: The National Health and Nutrition Examination Survey III (NHANES III)

    PubMed Central

    Asao, Keiko; Marekani, Amandine Sambira; VanCleave, Jessica; Rothberg, Amy E.

    2016-01-01

    Skipping breakfast is a common dietary habit considered to be unhealthy. However, the mechanisms underlying skipping breakfast have not been fully explored. Leptin is a hormone that regulates food intake and energy storage and secretes in a diurnal rhythm with lowest levels in the morning. We examined the association between the serum leptin level and skipping breakfast in 5714 adults in the U.S. National Health and Nutrition Examination Survey III, 1988–1994. We defined breakfast as any food or beverage consumed between 5:00 a.m. and 10:00 a.m. using a single 24-h recall. Skipped breakfast was seen in 13.1%. In the logistic regression models with and without adjusting for adiposity and sex, leptin levels were not associated with skipping breakfast. After adjusting for age, race/ethnicity, and time of venipuncture, the association remained insignificant. After further adjusting for potential confounders: physical activity, alcohol intake, smoking and diabetes and after further adjusting for: dietary factors, insulin and glucose levels, there was a 9% and 11%–12%, respectively, statistically significantly higher likelihood of skipping breakfast if the leptin level was more than 50% greater. Further investigation into the biological reasons for skipping breakfast may be useful for promoting healthy lifestyles. PMID:26927164

  10. Leptin level lowers in proportion to the amount of aerobic work after four weeks of training in obesity.

    PubMed

    Salvadori, A; Fanari, P; Brunani, A; Marzullo, P; Codecasa, F; Tovaglieri, I; Cornacchia, M; Palmulli, P; Longhini, E

    2015-03-01

    Leptin values are higher in obesity. Physical exercise reduces fat mass (FM) and decreases leptin levels. Intensity of physical training seems to play a role in reducing circulating leptin. In 16 obese subjects (8 men and 8 women, age 38.6±3.9 years, BMI 35.9±1.8 kg/m(2)), leptin was sampled before and after 4 weeks of controlled training. Eight subjects (4 men and 4 women) performed an aerobic training schedule (Group A), the remainders an aerobic training program with a bout of work beyond the anaerobic threshold (AT) (Group B). Training determined a reduction in leptin levels in both groups, which was significant in Group A (12.2 vs. 27.8 μg/l, p<0.05), even when related to the change in FM (0.372 vs. 0.762 μg/l/kg, p<0.05). FM decreased significantly in Group B when compared to Group A (-7.4 vs. -2.6 kg, respectively, p<0.001). While in Group A the slight loss of FM was aggregated to a significant decrease in leptin levels, the opposite occurred in Group B. In Group A, leptin lowering was proportional to the amount of total work performed (p<0.001, R(2)=0.89). In obesity, a reduction is observed in leptin levels after short-term training, which is seemingly dissociated from concomitant decrease of FM. Aerobic training alone appears to be linked to a greater leptin reduction, which is well correlated with the amount of work performed. PMID:25502942

  11. Are Volumetric Bone Mineral Density and Bone Micro-Architecture Associated with Leptin and Soluble Leptin Receptor Levels in Adolescent Idiopathic Scoliosis? – A Case-Control Study

    PubMed Central

    Tam, Elisa M. S.; Yu, Fiona W. P.; Hung, Vivian W. Y.; Liu, Zhen; Liu, King Lok; Ng, Bobby K. W.; Lee, Simon K. M.; Qiu, Yong; Cheng, Jack C. Y.; Lam, Tsz-Ping

    2014-01-01

    Background Adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD). The underlying etiology and how it may relate to the development of osteopenia remains unknown. Leptin has been postulated as one of the etiologic factors of AIS because of its profound effects on bone metabolism and pubertal growth. Its modulator, soluble leptin receptor (sOB-R), may affect leptin bioavailability and signaling. This study aimed to investigate whether serum leptin and sOB-R levels may be associated with bone quality, and whether these relationships may differ between young adolescent girls with and without AIS. Methods This was a case-control study involving 94 newly diagnosed AIS girls (Cobb angle 12–48°) aged 12 to 14 years old and 87 age and gender-matched normal controls. Subjects with BMI>23.0 Kg/m2 were excluded. Anthropometric measurements including body weight, height, arm span and sitting height were taken. Serum total leptin and sOB-R were assayed with ELISA. Non-dominant distal radius was scanned with High Resolution pQCT for assessing bone quality in terms of bone morphometry, volumetric BMD (vBMD) and trabecular bone micro-architecture. Results Compared with normal controls, AIS girls had numerically higher sOB-R (p = 0.006), lower average vBMD (p = 0.048), lower cortical vBMD (p = 0.029), higher cortical bone perimeter (p = 0.014) and higher trabecular area (p = 0.027), but none remained statistically significant after the Hochberg-Benjamini procedure. Correlation analysis on serum leptin level indicated that distinctive correlations with trabecular bone parameters occurred only in AIS. Conclusion This study showed that bone quality in AIS girls was deranged as compared with controls. In addition, the distinct differences in correlation pattern between leptin and trabecular bone parameters indicated possible abnormalities in bone metabolism and dysfunction of the leptin signaling pathway in AIS. PMID:24516571

  12. Low leptin levels predict amenorrhea in underweight and eating disordered females.

    PubMed

    Köpp, W; Blum, W F; von Prittwitz, S; Ziegler, A; Lübbert, H; Emons, G; Herzog, W; Herpertz, S; Deter, H C; Remschmidt, H; Hebebrand, J

    1997-07-01

    Evidence that leptin plays an important role in reproductive function is accumulating rapidly. We hypothesized that low leptin synthesis is associated with amenorrhea. We therefore determined serum leptin levels in 43 underweight female students, who were screened for lifetime occurrence of amenorrhea. We assessed the predictive value of leptin, body mass index (BMI), fat mass and percent body fat, respectively, for lifetime occurrence of amenorrea. Factors predicting amenorrhea were tested for their capability to predict current amenorrhea in a second cohort of 63 inpatients with anorexia nervosa (AN) or bulimia nervosa (BN). Furthermore, the relationships between serum leptin levels and of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone, respectively, were evaluated. Only leptin predicted lifetime occurrence of amenorrhea in the student cohort. The critical leptin level was in the range of 1.85 micrograms L-1. This level served to largely separate anorectic from bulimic patients. In patients with AN mean serum log10 leptin levels over the first 4 weeks of inpatient treatment were correlated with mean FSH, LH and estradiol levels, respectively. Evidently, a critical leptin level is needed to maintain menstruation. In affluent populations eating disorders are likely to be a major cause of a low leptin synthesis. PMID:9246675

  13. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    PubMed

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  14. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    PubMed Central

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  15. Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population

    PubMed Central

    2014-01-01

    Background This study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak. Methods Convenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results The LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations. Conclusions The LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity

  16. Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome

    PubMed Central

    2014-01-01

    Background Metabolic syndrome is a cluster of metabolic risk factors including dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF (Brain-derived neurotrophic factor) and leptin have been implied in the energy homeostasis. The purposes of this study were to examine concentrations of leptin, BDNF and biochemical parameters in metabolic-syndrome subjects and healthy controls, and also to search for associations of leptin gene (LEP) G2548A, leptin receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with leptin levels, BDNF levels and metabolic syndrome among Thais. Methods The case-controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome subjects; 162 controls) during the health screening program. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and BDNF Val66Met was carried out using polymerase chain reaction-restriction fragment length polymorphism technique. Results Serum leptin levels were significantly higher in the metabolic-syndrome group than the control group (p < 0.01), but the BDNF difference between them was not significant. Significant associations of LEPR Gln223Arg polymorphism were found with leptin and glucose levels (p < 0.05), after adjusting for potential covariates. This LEPR polymorphism in the metabolic-syndrome group was also significantly more frequent than in the control group (p < 0.05). However, other gene polymorphisms, LEP G2548A and BDNF Val66Met, showed no significant relationship with leptin levels, BDNF levels or metabolic syndrome. Conclusion These findings suggest leptin levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted leptin concentrations, and this gene polymorphism may influence susceptibility to metabolic syndrome among

  17. Differential Acute and Chronic Effects of Leptin on Hypothalamic Astrocyte Morphology and Synaptic Protein Levels

    PubMed Central

    García-Cáceres, Cristina; Fuente-Martín, Esther; Burgos-Ramos, Emma; Granado, Miriam; Frago, Laura M.; Barrios, Vicente; Horvath, Tamas

    2011-01-01

    Astrocytes participate in neuroendocrine functions partially through modulation of synaptic input density in the hypothalamus. Indeed, glial ensheathing of neurons is modified by specific hormones, thus determining the availability of neuronal membrane space for synaptic inputs, with the loss of this plasticity possibly being involved in pathological processes. Leptin modulates synaptic inputs in the hypothalamus, but whether astrocytes participate in this action is unknown. Here we report that astrocyte structural proteins, such as glial fibrillary acidic protein (GFAP) and vimentin, are induced and astrocyte morphology modified by chronic leptin administration (intracerebroventricular, 2 wk), with these changes being inversely related to modifications in synaptic protein densities. Similar changes in glial structural proteins were observed in adult male rats that had increased body weight and circulating leptin levels due to neonatal overnutrition (overnutrition: four pups/litter vs. control: 12 pups/litter). However, acute leptin treatment reduced hypothalamic GFAP levels and induced synaptic protein levels 1 h after administration, with no effect on vimentin. In primary hypothalamic astrocyte cultures leptin also reduced GFAP levels at 1 h, with an induction at 24 h, indicating a possible direct effect of leptin. Hence, one mechanism by which leptin may affect metabolism is by modifying hypothalamic astrocyte morphology, which in turn could alter synaptic inputs to hypothalamic neurons. Furthermore, the responses to acute and chronic leptin exposure are inverse, raising the possibility that increased glial activation in response to chronic leptin exposure could be involved in central leptin resistance. PMID:21343257

  18. Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: effects on leptin levels.

    PubMed

    Lindgärde, Folke; Widén, Iréne; Gebb, Miriam; Ahrén, Bo

    2004-10-01

    Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agriculture involve a change of body composition, plasma leptin concentration, and markers of the metabolic syndrome. A total of 59 healthy Shuar Amerindian women living in 5 isolated communities in the Ecuadorian Amazonian rain forest were examined. Women (n = 33) from the largest and oldest community, Yuwientsa, who are more dependent on agriculture had higher fat mass (11.7 +/- 3.3 v 14.5 +/- 4.0 kg; P = .023) but the same body mass index (24.1 +/- 2.7 v 23.1 +/- 2.8 kg/m2; not significant [NS]) and lean body mass (41.0 +/- 5.0 v 40.2 +/- 6.2 kg; NS) than women (n = 26) from the 4 traditional hunter/gather settlements. Furthermore, women from Yuwientsia had higher leptin (5.5 +/- 3.1 v 4.1 +/- 2.7 ng/mL; P = .021) and plasma insulin levels (49.8 +/- 37.4 v 35.5 +/- 12.7 pmol/L; P = .013). Homeostasis model assessment (HOMA) values (8.8 +/- 4.8 v 6.1 +/- 2.2; P = .004) and plasma triglyceride levels (2.3 +/- 1.0 v 1.7 +/- 0.6 mmol/L; P = .025) as markers of the metabolic syndrome were also increased in the Yuwientsa population. Mean plasma glucagon concentrations were not different between the groups. We conclude that body fat and levels of insulin and leptin are higher in the population more dependent on agriculture for living. In fact, the leptin concentrations from the 4 hunter/gather communities are the lowest mean value ever reported from a population of healthy females. As there are no genetic or biologic differences between the Shuar Indians from the 5 communities, we hypothesize that behavioral responses to a changing environment may be the key to the development of

  19. Oncogenic role of leptin and Notch interleukin-1 leptin crosstalk outcome in cancer

    PubMed Central

    Lipsey, Crystal C; Harbuzariu, Adriana; Daley-Brown, Danielle; Gonzalez-Perez, Ruben R

    2016-01-01

    Obesity is a global pandemic characterized by high levels of body fat (adiposity) and derived-cytokines (i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin’s main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1 (IL-1) [Notch, IL-1 and leptin crosstalk outcome (NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers. PMID:27019796

  20. Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer

    PubMed Central

    Marcello, Marjory Alana; Calixto, Antonio Ramos; de Almeida, Jacqueline Fatima Martins; Cunha, Lucas Leite; Cavalari, Camila Ayume Amano; Etchebehere, Elba C. S.; da Assumpção, Ligia Vera Montalli; Geloneze, Bruno; Carvalho, Andre Lopes; Ward, Laura Sterian

    2015-01-01

    Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516–90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161–12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426–20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness. PMID:25810718

  1. Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer.

    PubMed

    Marcello, Marjory Alana; Calixto, Antonio Ramos; de Almeida, Jacqueline Fatima Martins; Martins, Mariana Bonjiorno; Cunha, Lucas Leite; Cavalari, Camila Ayume Amano; Etchebehere, Elba C S; da Assumpção, Ligia Vera Montalli; Geloneze, Bruno; Carvalho, Andre Lopes; Ward, Laura Sterian

    2015-01-01

    Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin (9.22 ± 0.98 ng/mL) than those with AG genotype (10.07 ± 0.60 ng/mL; P = 0.005). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels (10.05 ± 0.59 ng/mL) than the subjects with GG genotype (9.52 ± 0.79 ng/mL; P < 0.05). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; P = 0.0183; 95% CI, 1.516-90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; P = 0.027; 95% CI, 1.161-12.092 and OR, 5.437; P = 0.013; 95% CI, 1.426-20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness. PMID:25810718

  2. Effects of a 6-month infliximab treatment on plasma levels of leptin and adiponectin in patients with rheumatoid arthritis.

    PubMed

    Derdemezis, Christos S; Filippatos, Theodosios D; Voulgari, Paraskevi V; Tselepis, Alexandros D; Drosos, Alexandros A; Kiortsis, Dimitrios N

    2009-10-01

    Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (TNF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels. PMID:19563510

  3. Elevated plasma leptin levels of fasted rainbow trout decrease rapidly in response to feed intake.

    PubMed

    Johansson, Marcus; Björnsson, Björn Thrandur

    2015-04-01

    Leptin has an anorexigenic effect in fish, indicating a role in regulation of growth and energy homeostasis. The study aimed to further clarify the physiological role of leptin in rainbow trout, specifically its short-term response to feed intake after a period of fasting. Utilizing a salmonid leptin radioimmunoassay, the study demonstrates differences in plasma leptin levels in fishes with different nutritional status and at the onset of feeding. Some of the fasted fish were clearly in a state of anorexia, and did not initiate feeding during the 72h refeeding period. For those fish that did initiate feeding, both previously fed and fasted, plasma leptin levels rapidly decreased during the first 24h in correlation with increased amount of food reaching the gastrointestinal tract, while non-feeding individuals retained a high plasma leptin levels. The data indicate that the leptin-induced anorexic state is broken after onset of feeding and that the regulatory mechanisms leading to decreased plasma leptin levels are linked to nutrient levels. PMID:25745812

  4. Evaluation of Salivary Leptin Levels in Healthy Subjects and Patients with Advanced Periodontitis

    PubMed Central

    Khorsand, Afshin; Bayani, Mojtaba; Torabi, Sepehr; Kharrazifard, Mohammad Javad; Mohammadnejhad, Fatemeh

    2016-01-01

    Objectives: Leptin is a hormone-like protein produced by the adipose tissue. It plays an important role in protection of host against inflammation and infection. Some studies have reported changes in leptin levels in the gingival crevicular fluid (GCF), saliva and blood serum of patients with periodontal disease compared to healthy individuals. The aim of the present study was to compare the salivary leptin levels in patients with advanced periodontitis and healthy individuals. Materials and Methods: In this case-control study, the salivary samples of healthy individuals and patients with advanced periodontitis with clinical attachment loss >5mm were obtained using a standardized method and the leptin levels were measured in the salivary samples by means of ELISA. The effects of the periodontal status and sex on the salivary leptin levels of both groups were statistically analyzed by two-way ANOVA. Results: The means ± standard deviation (SD) of salivary leptin levels in healthy subjects and patients with advanced periodontitis were 34.27±6.88 and 17.87±5.89 pg/mL, respectively. Statistical analysis showed that the effect of sex on the salivary leptin levels was not significant (P=0.91), while the effect of advanced periodontitis on the salivary leptin levels was significant compared to healthy individuals (P<0.0001). Conclusions: In patients with advanced periodontitis, the salivary leptin levels were significantly lower compared to healthy individuals. Thus, assessment of salivary leptin can be done as a non-invasive and simple method to determine the susceptibility of patients to advanced periodontitis. PMID:27536322

  5. Circulating Irisin Levels Are Not Regulated by Nutritional Status, Obesity, or Leptin Levels in Rodents

    PubMed Central

    Quiñones, Mar; Folgueira, Cintia; Sánchez-Rebordelo, Estrella; Al-Massadi, Omar

    2015-01-01

    Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5) that is mainly released by skeletal muscle and was proposed to mediate the beneficial effects of exercise on metabolism. In the present study we aim to investigate the regulation of the circulating levels of irisin in obese animal models (diet-induced obese (DIO) rats and leptin-deficient (ob/ob) mice), as well as the influence of nutritional status and leptin. Irisin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). Serum irisin levels remained unaltered in DIO rats and ob/ob mice. Moreover, its circulating levels were also unaffected by fasting, leptin deficiency, and exogenous leptin administration in rodents. In spite of these negative results we find a negative correlation between irisin and insulin in DIO animals and a positive correlation between irisin and glucose under short-term changes in nutritional status. Our findings indicate that serum irisin levels are not modulated by different physiological settings associated to alterations in energy homeostasis. These results suggest that in rodents circulating levels of irisin are not involved in the pathophysiology of obesity and could be unrelated to metabolic status; however, further studies should clarify its precise role in states of glucose homeostasis imbalance. PMID:26568663

  6. Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status?

    PubMed Central

    Perfetto, F; Tarquini, R; Simonini, G; Bindi, G; Mancuso, F; Guiducci, S; Matucci-Cerinic, M; Falcini, F

    2005-01-01

    Objective: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA. Methods: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls. Results: Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m2; p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively). Conclusions: Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA. PMID:15608316

  7. Monitoring leptin activity using the chicken leptin receptor.

    PubMed

    Hen, Gideon; Yosefi, Sera; Ronin, Ana; Einat, Paz; Rosenblum, Charles I; Denver, Robert J; Friedman-Einat, Miriam

    2008-05-01

    We report on the construction of a leptin bioassay based on the activation of chicken leptin receptor in cultured cells. A human embryonic kidney (HEK)-293 cell line, stably transfected with the full-length cDNA of chicken leptin receptor together with a STAT3-responsive reporter gene specifically responded to recombinant human and Xenopus leptins. The observed higher sensitivity of chicken leptin receptor to the former is in agreement with the degree of sequence similarity among these species (about 60 and 38% identical amino acids between humans and chickens, and between humans and Xenopus respectively). The specific activation of signal transduction through the chicken leptin receptor, shown here for the first time, suggests that the transition of Gln269 (implicated in the Gln-to-Pro Zucker fatty mutation in rats) to Glu in chickens does not impair its activity. Analysis of leptin-like activity in human serum samples of obese and lean subjects coincided well with leptin levels determined by RIA. Serum samples of pre- and post partum cows showed a tight correlation with the degree of adiposity. However, specific activation of the chicken leptin receptor in this assay was not observed with serum samples from broiler or layer chickens (representing fat and lean phenotypes respectively) or with those from turkey. Similar leptin receptor activation profiles were observed with cells transfected with human leptin receptor. Further work is needed to determine whether the lack of leptin-like activity in the chicken serum samples is due to a lack of leptin in this species or simply to a serum level of leptin that is below the detection threshold. PMID:18434362

  8. Peripheral Signals of Food Intake in Response to Low Leptin Levels Induced by Centrifugation

    NASA Technical Reports Server (NTRS)

    Moran, M. M.; Wade, Charles E.; Stein, T. P.; Dalton, Bonnie P. (Technical Monitor)

    2001-01-01

    The focus of the study was to examine leptin and other peripheral signals of energy balance, following hypergravity. The study was conducted in two experiments. In experiment 1 rats were centrifuged at either 1.5, 2, or remained at 1 G. During days 8 to 14 of experiment 1, mean body mass of the 1.5 and 2 G groups was significantly (p<0.05) lower than controls. No differences were found in food intake (g/day/100 g body mass). Epididymal fat in the 2 G group was 21% lower than controls and 14% lower than the 1.5 G group. Plasma leptin was reduced from controls in the 1.5 and 2 G groups by 45 and 63%, respectively. A significant correlation was found between G load and urinary catecholamines. In experiment 2, rats were centrifuged at either 1.25, 1.5, or remained at 1 G. During days 8 to 14, body mass and food intake were similar between the 1, 1.25, and 1.5 G groups. Epididymal fat was reduced from controls in the 1.25 (14%) and 1.5 (19%) G groups. Leptin was reduced from controls in the 1.25 (45%) and 1.5 (46%) G groups. No differences were found in urinary epinephrine. Urinary norepinephrine levels were significantly higher than controls in each centrifuge group. During hypergravity exposure, food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  9. Evaluation of Serum Leptin Levels and Growth in Patients with β-Thalassaemia Major

    PubMed Central

    Al-Naama, Lamia Mustafa; Hassan, Meaad Kadum; Abdul Karim, Muhannad Maki

    2016-01-01

    Background. Iron deposition in the body can damage the endocrine glands of patients with β-thalassaemia major (β-TM). Leptin plays a key role in the regulation of appetite, body fat mass, and endocrine function. Objectives. This study aimed to evaluate the relationship between serum leptin and growth and pubertal development in patients with β-TM, as well as whether serum leptin can predict growth retardation and delayed puberty in these patients. Methods. Fifty β-TM patients (aged 8–20 years) and 75 age-matched healthy controls were recruited. Anthropometric data and sexual maturity ratings were assessed. Serum leptin was measured by ELISA. Results. Serum leptin levels were significantly lower in patients with β-TM than in healthy individuals (P < 0.001). Leptin levels were also significantly reduced in female patients with short stature (P < 0.002) and in patients who displayed delayed puberty (P = 0.032) compared to those with normal stature who had reached puberty. The sensitivity of leptin for predicting short stature and delayed puberty among patients was 84.6% and 92.3%, respectively. Conclusion. Low serum leptin is sensitive to predict short stature and significant in β-TM females only. This link could thus be used as a guide for further therapeutic or hormonal modulation. PMID:27088012

  10. Correlation between serum leptin level and thyroid hormones in children with major beta-thalassemia 

    PubMed Central

    Shahramian, I; Noori, NM; Ramezani, AA; Sharafi, E; Akhlaghi, E

    2013-01-01

    Background Beta-thalassemia is the most common hematology disease in human and leptin is one of the hormone that produce by adiposities cells. The purpose of this study was to investigate the relationship between serum leptin level and thyroid hormones in children with major beta-thalassemia. Materials and Methods This descriptive-cross sectional study was performed on 90 children aged 6-16 years old with beta-thalassemia. Body Mass Index (BMI ) were meuseurd in all patients and then, after collecting the samples, leptin and thyroid hormones levels of the serum were measured in the patients with thalassemia via ELISA method. Then, all data was analyzed by Pearson correlation test, and x2 statistical tests and P < 0.05 was considered as a significant difference. Results The mean of body mass index and serum leptin level in the patients group was 16.58±2.43 and 1.521 ±2. 49, respectively. The mean serum levels of thyroxin (T4), triiodothyronine (T3), and thyroid- stimulating hormone (TSH) in patient's groups were7.94 ±3.56, 1.28 ± 0.46, and 2.85 ±3. 44, respectively. There was significant correlation between serum leptin levels and T4 in patients with major thalassemia; also there was no significant correlation between serum leptin level and T3and TSH. There was a significant correlation was between the leptin serum level and BMI in patients (P value=0.008). Conclusion The results of this study demonstrated that in patients with major thalassemia, there was significant correlation between serum leptin level and thyroxin hormone. Leptin level has more relationship with thyroxin than thyroid- stimulating hormone. PMID:24575288

  11. Hormonal modulation of food intake in response to low leptin levels induced by hypergravity

    NASA Technical Reports Server (NTRS)

    Moran, M. M.; Stein, T. P.; Wade, C. E.

    2001-01-01

    A loss in fat mass is a common response to centrifugation and it results in low circulating leptin concentrations. However, rats adapted to hypergravity are euphagic. The focus of this study was to examine leptin and other peripheral signals of energy balance in the presence of a hypergravity-induced loss of fat mass and euphagia. Male Sprague-Dawley rats were centrifuged for 14 days at gravity levels of 1.25, 1.5, or 2 G, or they remained stationary at 1 G. Urinary catecholamines, urinary corticosterone, food intake, and body mass were measured on Days 11 to 14. Plasma hormones and epididymal fat pad mass were measured on Day 14. Mean body mass of the 1.25, 1.5, and 2 G groups were significantly (P < 0.05) lower than controls, and no differences were found in food intake (g/day/100 g body mass) between the hypergravity groups and controls. Epididymal fat mass was 14%, 14%, and 21% lower than controls in the 1.25, 1.5, and 2.0 G groups, respectively. Plasma leptin was significantly reduced from controls by 46%, 45%, and 65% in the 1.25, 1.5, and 2 G groups, respectively. Plasma insulin was significantly lower in the 1.25, 1.5, and 2.0 G groups than controls by 35%, 38%, and 33%. No differences were found between controls and hypergravity groups in urinary corticosterone. Mean urinary epinephrine was significantly higher in the 1.5 and 2.0 G groups than in controls. Mean urinary norepinephrine was significantly higher in the 1.25, 1.5 and 2.0 G groups than in controls. Significant correlations were found between G load and body mass, fat mass, leptin, urinary epinephrine, and norepinephrine. During hypergravity exposure, maintenance of food intake is the result of a complex relationship between multiple pathways, which abates the importance of leptin as a primary signal.

  12. Lipometer subcutaneous adipose tissue topography (SAT-Top) reflects serum leptin levels varying in circadian rhythms

    NASA Astrophysics Data System (ADS)

    Moeller, Reinhard; Tafeit, Erwin; Sudi, Karl; Vrecko, Karoline; Horejsi, Renate; Hinghofer-Szalkay, Helmut G.; Reibnegger, Gilbert

    1998-05-01

    Recent advances in obesity research have shown that the product of the ob-gene named leptin is related to total body fast mass in humans. There is, however, a debate if leptin levels are pulsatile and linked to body fat distribution. In this study we therefore investigated the subcutaneous adipose tissue topography (SAT-Top) measured by means of the newly developed device Lipometer and leptin levels during a 24 hours beginning at 0715am ending the same time in the next day. Blood samples for measurement of leptin were taken every 3 hours in a male subject. Measurements of SAT-Top were performed at 15 body sites from neck to calf at the left and right body site at the same time interval. We observed an almost symmetrically reaction of the left and right body site with a maximum of the mean value of all body sites in the evening at 0715pm. There was a negative correlation between serum leptin levels and SAT-Top using the set of certain body sites (R2 equals 0.80, p equals 0.01). If these combination of body sites is inversed and set against serum leptin levels, both curves show almost identical shape and time dependence. We conclude that SAT-Top by means of Lipometer is changed in a short time and related to leptin levels in the investigated male subject.

  13. The Association between Leptin Level and Breast Cancer: A Meta-Analysis

    PubMed Central

    Guo, Weiheng; Shao, Liang; Liu, Yi; Wang, Liqin

    2013-01-01

    Background Contradictory results have been reported regarding the association between leptin level and breast cancer. Therefore, a meta-analysis was performed to investigate this issue. Methods Published literature from PubMed and the Chinese National Knowledge Infrastructure (CNKI) Database was retrieved. This study was performed based on different cases and control groups. The combined effect () with 95% confidence interval (CI) was calculated using fixed-effects or random-effects model analysis. Results Overall, the mean serum leptin level of case groups was significantly higher than that of control groups. A) For 9 studies comparing breast cancer cases and healthy controls the combined effect was 0.58 with 95% CI (0.48, 0.68). B) For 4 studies comparing premenopausal breast cancer cases and healthy controls the was 0.32 (0.12, 0.52). C) For 5 studies comparing postmenopausal cases and healthy controls the was 0.65 (0.46, 0.84). D) For 4 studies comparing breast cancer cases and breast benign controls the was 0.38 (0.17, 0.59). E) For 2 studies comparing premenopausal breast cancer cases and breast benign controls the was 0.33 (-0.25, 0.91). F) For 6 studies comparing postmenopausal breast cancer cases and breast benign controls the was 0.39 (0.19, 0.60). G) For 4 studies comparing lymph node metastasis positive cases and negative controls the was 0.72 (0.45, 1.00). H) For 3 studies comparing breast benign cases and healthy controls the was 0.71 (0.41, 1.01). Conclusion This meta-analysis suggests that leptin level plays a role in breast cancer and has potential for development as a diagnostic tool. PMID:23826274

  14. Developing Higher Level Thinking

    ERIC Educational Resources Information Center

    Limbach, Barbara; Waugh, Wendy

    2010-01-01

    This paper identifies an interdisciplinary, five-step process, built upon existing theory and best practices in cognitive development, effective learning environments, and outcomes-based assessment. The "Process for the Development of Higher Level Thinking Skills" provides teachers with an easy to implement method of moving toward a more…

  15. Association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer

    PubMed Central

    Jin, Jing Hui; Kim, Hyun-Jung; Kim, Chan Young; Kim, Yun Hwan; Ju, Woong

    2016-01-01

    Objective Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer. Methods For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Student's t-test; correlations were confirmed using the Pearson correlation. Results The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078). Conclusion Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated. PMID:27462594

  16. Selenium and leptin levels in febrile seizure: a case-control study in children

    PubMed Central

    Khoshdel, Abolfazl; Abbasi, Maedeh

    2013-01-01

    Purpose Febrile seizures (FS) are seizures that occur between the age of 6 and 60 months, but its pathophysiology still is not fully understood. There is limited information about the correlation between levels of selenium and leptin with FS. This study aimed to determine the relationship between serum levels of selenium and leptin in children with FS. Methods This case-control study was conducted in a University Hospital in Shahrekord, Iran, in 2011. The serum levels of selenium and leptin of 25 children with simple febrile seizure (case group) were compared with 25 febrile children without seizure (control group) in acute phase and after three months. The levels of serum selenium and leptin were measured by flame atomic absorption spectrophotometer and enzyme-linked immunosorbent assay method, respectively. Results In acute phase, the mean serum level of selenium in case and control groups were 95.88±42.55 and 113.25±54.43 µg/dL, respectively, and difference was not significant (P=0.415), but after three months, this level had a significant increase in both groups (P<0.001). In acute phase, the mean serum leptin level in case and control groups were 0.94±0.5 and 0.98±0.84 ng/mL, respectively, but difference was not significant (P=0.405). After three months, serum leptin level had no significant change in both groups (P=0.882). Conclusion These observations suggest that serum levels of selenium and leptin have not specific relation with FS but overllay is lower, however, further study is recommended. Also selenium level in stress and acute phase was significantly lower than recovery phase. PMID:23482826

  17. Serum leptin level in children with atopic dermatitis-treated topical steroids.

    PubMed

    Bostanci, Ilknur; Atli, Ozlem; Celebi, Nermin; Taşar, Ayşin; Alpkarakoç, Esra; Dallar, Yildiz

    2004-06-01

    Leptin, the obese gene product, is a 16-kDa peptide hormone secreted by adiposities. Systemic administration of exogenous glucocorticoids has been found to increase circulating leptin levels. In this study, we aimed to assess serum leptin in children with atopic dermatitis (AD)-treated with local steroids. Twenty children with AD were included during the 2001-2002 time period. The study was conducted prospectively. Atopy was defined as the presence of at least one aeroallergen-specific immunoglobulin E (IgE) antibody. Serum leptin was determined using a commercially available radioimmunoassay kit with 3.4-8.3% intra-assay and 3.0-6.2% interassay coefficients of variation, and 0.5 ng/ml sensitivity. Fourteen boys and six girls with AD, the mean age of the patients was 3.1 +/- 2.2. Forty-three percentage of the family histories for atopy were positive, 60% of the cases passive smoking histories were positive. In seven patients the aeroallergen-specific IgE were positive. All 20 patients treated clobetasone 17-butirate (0.05%). There was no significant difference in serum leptin between patients (mean +/- s.d.: 4.6 +/- 3.8), and controls (mean +/- s.d.: 6.2 +/- 3.6) (p > 0.05). Local steroid does not influence circulating leptin levels, suggesting that regulation of body weight is unaffected. PMID:15209961

  18. Leptin signaling and Alzheimer’s disease

    PubMed Central

    Marwarha, Gurdeep; Ghribi, Othman

    2012-01-01

    Leptin, an adipocytokine produced in the peripheral system as well as in the brain, is implicated in obesity, food intake, glucose homeostasis, and energy expenditure. Leptin expression levels and signaling pathways may also be linked to the pathophysiology of neurodegenerative diseases including Alzheimer’s disease. Epidemiological studies have demonstrated that higher circulating leptin levels are associated with lower risk of dementia including Alzheimer’s disease, and lower circulating levels of leptin have been reported in patients with Alzheimer’s disease. Leptin receptors are highly expressed in the hippocampus, a brain area involved in learning and memory and severely affected during the course of Alzheimer’s disease. In laboratory studies, several in vivo and in vitro studies have shown that leptin supplementation decreases amyloid-β (Aβ) production and tau phosphorylation, two major biochemical events that play a key role in the pathogenesis of Alzheimer’s disease. In this review, we will review the structure of leptin, the type of receptors of leptin in the brain, the various biological functions attributed to this adipocytokine, the signaling pathways that govern leptin actions, and the potential role of leptin in the pathophysiology of Alzheimer’s disease. Leptin exerts its functions by binding to the leptin receptor (ObR). This binding can involve several signaling pathways including JAK/STAT pathway, ERK pathway and the PI3K/Akt/mTOR Pathway. Modulation of these pathways leads to the regulation of a multitude of functions that define the intricate involvement of leptin in various physiological tasks. In this review, we will specifically relate the potential involvement of leptin signaling in Alzheimer’s disease based on work published by several laboratories including ours. All this work points to leptin as a possible target for developing supplementation therapies for reducing the progression of Alzheimer’s disease. PMID:23383396

  19. The effects of prolonged fasting on the levels of adiponectin, leptin, apelin, and omentin in pregnant women.

    PubMed

    Kiyak Caglayan, Emel; Engin-Ustun, Yaprak; Sari, Nagihan; Gocmen, Ayşe Yesim; Polat, M Fevzi

    2016-05-01

    The aim of the present study was to evaluate serum adiponectin, leptin, apelin and omentin levels to explore metabolic changes occurring during fasting in the month of Ramadan. The study was designed as a prospective study. The patients were divided into two groups, each comprising 20 patients: Group I, fasting pregnant women, and Group II, non-fasting pregnant women. The patients' age, parity, gestational week and body mass index were recorded. Adiponectin and omentin levels were significantly lower in fasting pregnant women (p < 0.001). When the two groups were compared in terms of serum leptin and apelin levels, both were found to be significantly higher in Group I than in Group II. The findings of the present study suggest that pregnant women who are willing to fast during 24-38 weeks' gestation should be informed about insulin resistance. PMID:26759187

  20. Smoking Habits and Neuropeptides: Adiponectin, Brain-derived Neurotrophic Factor, and Leptin Levels.

    PubMed

    Kim, Ki-Woong; Won, Yong Lim; Ko, Kyung Sun; Roh, Ji Won

    2014-06-01

    This study aimed to identify changes in the level of neuropeptides among current smokers, former smokers, and individuals who had never smoked, and how smoking habits affect obesity and metabolic syndrome (MetS). Neuropeptide levels, anthropometric parameters, and metabolic syndrome diagnostic indices were determined among male workers; 117 of these had never smoked, whereas 58 and 198 were former and current smokers, respectively. The total sample comprised 373 male workers. The results obtained from anthropometric measurements showed that current smokers attained significantly lower body weight, body mass index, waist circumference, and abdominal fat thickness values than former smokers and those who had never smoked. Current smokers' eating habits proved worse than those of non-smokers and individuals who had never smoked. The level of brain-derived neurotrophic factor (BDNF) in the neuropeptides in the case of former smokers was 23.6 ± 9.2 pg/ml, higher than that of current smokers (20.4 ± 6.1) and individuals who had never smoked (22.4 ± 5.8) (F = 6.520, p = 0.002). The level of adiponectin among former smokers was somewhat lower than that of current smokers, whereas leptin levels were higher among former smokers than current smokers; these results were not statistically significant. A relationship was found between adiponectin and triglyceride among non-smokers (odds ratio = 0.660, β value = -0.416, p < 0.01) and smokers (odds ratio = 0.827, β value = -0.190, p < 0.05). Further, waist circumference among non-smokers (odds ratio = 1.622, β value = 0.483, p < 0.001) and smokers (odds ratio = 1.895, β value = 0.639, p < 0.001) was associated with leptin. It was concluded that cigarette smoking leads to an imbalance of energy expenditure and appetite by changing the concentration of neuropeptides such as adiponectin, BDNF, leptin, and hsCRP, and influences food intake, body weight, the body mass index, blood pressure, and abdominal fat, which are risk

  1. Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy*

    PubMed Central

    Ruszkowska, Barbara; Sokup, Alina; Kulwas, Arleta; Socha, Maciej W.; Góralczyk, Krzysztof; Góralczyk, Barbara; Rość, Danuta

    2012-01-01

    Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to

  2. The Response of Circulating Leptin Levels to Exercise Stress Testing in Subjects Diagnosed with Metabolic Syndrome

    PubMed Central

    Pop, Dana; Dădârlat, Alexandra; Bodizs, Gyorgy; Stanca, Liana; Zdrenghea, Dumitru

    2014-01-01

    Aim. To assess the plasma leptin responses after exercise stress testing in patients with metabolic syndrome (MS). Material and Methods. We investigated 67 patients with MS, with mean age of 55 ± 7 years. They underwent exercise stress testing on cycloergometer. The lot was divided into three groups: group 1—10 patients with a true positive test, group 2—18 patients with a true negative test, and group 3—39 patients with a false negative test. Leptin levels were measured using the ELISA method. Results. Leptin levels decreased after effort in patients with MS (9.42 ± 11.08 ng/mL before and 8.18 ± 11.5 ng/mL after the exercise stress test, P = 0.0005, r = 0.874). In groups 1 (8.98 ± 9.09 at rest versus 5.98 ± 8.73 ng/mL after the exercise test, P = 0.002) and 3 (8.6 ± 10.53 at rest versus 6.91 ± 9.07 ng/mL, P = 0.0005), lower leptin levels were recorded immediately after exercise testing. Leptin levels were not significantly lower in group 2 before effort (9.49 ± 11.36 ng/ml) and after (9.46 ± 13.81 ng/mL). We found no correlation between leptinemia and exercise stress testing parameters, regardless of group. Conclusion. Our research showed that short-term exercise lowers leptin levels in coronary patients, without a relationship between its parameters and leptin values. PMID:24616817

  3. Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis

    PubMed Central

    Nicholson, James; Azim, Syed; Rebecchi, Mario J.; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J.; Benveniste, Helene; Kaczocha, Martin

    2015-01-01

    Background There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Methodology/Principal Findings Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography – mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman’s ρ -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. Conclusions/Significance In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior. PMID:25835291

  4. Preoperative plasma leptin levels predict delirium in elderly patients after hip fracture surgery.

    PubMed

    Chen, Xue-Wu; Shi, Jun-Wu; Yang, Ping-Shan; Wu, Zhu-Qi

    2014-07-01

    Leptin is considered to be a modulator of the immune response. Hypoleptinemia increases the risk for Alzheimer's disease and vascular dementia. The present study aimed to investigate the ability of plasma leptin level to predict delirium in elderly patients after hip fracture surgery. Postoperative delirium (pod) was evaluated using the Confusion Assessment Method. Prolonged postoperative delirium (ppod) was defined as delirium lasting more than 4 weeks. Plasma leptin levels of 186 elderly patients and 186 elderly controls were measured by an enzyme-linked immunosorbent assay. Plasma leptin level was substantially lower in patients than in controls (4.6±2.2ng/ml vs. 7.5±1.8ng/ml, P<0.001). It was identified as an independent predictor for pod [odds ratio, 0.385; 95% confidence interval (CI), 0.286-0.517; P<0.001] and ppod (odds ratio, 0.283; 95% CI, 0.152-0.527; P<0.001) using a multivariate analysis, and had high area under receiver operating characteristic curve for pod [area under curve (AUC), 0.850; 95% CI, 0.790-0.898] and ppod (AUC, 0.890; 95% CI, 0.836-0.931). The predictive value of leptin was markedly bigger than that of age for pod (AUC, 0.705; 95% CI, 0.634-0.770; P=0.002) and ppod (AUC, 0.713; 95% CI, 0.642-0.777; P=0.019). In a combined logistic-regression model, leptin improved the AUC of age to 0.890 (95% CI, 0.836-0.931) (P<0.001) for pod and 0.910 (95% CI, 0.860-0.947) (P=0.005) for ppod. Thus, preoperative plasma leptin level may be a useful, complementary tool to predict delirium and also prolonged delirium in elderly patients after hip fracture surgery. PMID:24787655

  5. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID:26162700

  6. Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin

    PubMed Central

    Remla, Nesrine; Hadjidj, Zeyneb; Ghezzaz, Kamel; Moulessehoul, Soraya; Aribi, Mourad

    2016-01-01

    Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56–193.32; p = 0.007]; OR = 16 [95% CI, 1.69–151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06–37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64–20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin. PMID:27413547

  7. The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance

    PubMed Central

    Uzun, Hakan; Bitik, Ozan; Baltu, Yahya; Sönmez, Çiğdem; Öztürk Kaymak, Ayşegül

    2015-01-01

    Background. The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance. Methods. 42 obese female patients who had gigantomastia were operated on. We recorded patients' demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference. Results. Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively. Conclusion. Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk. PMID:26550014

  8. The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance.

    PubMed

    Uzun, Hakan; Bitik, Ozan; Baltu, Yahya; Sönmez, Çiğdem; Öztürk Kaymak, Ayşegül

    2015-01-01

    Background. The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance. Methods. 42 obese female patients who had gigantomastia were operated on. We recorded patients' demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference. Results. Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively. Conclusion. Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk. PMID:26550014

  9. Diurnal intermittent fasting during Ramadan: the effects on leptin and ghrelin levels.

    PubMed

    Alzoghaibi, Mohammed A; Pandi-Perumal, Seithikurippu R; Sharif, Munir M; BaHammam, Ahmed S

    2014-01-01

    We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting. PMID:24637892

  10. Sustained high levels of serum leptin rather than IL-6 observed in patients with postpartum thyroiditis during their first postpartum year.

    PubMed

    Guo, Huiling; Liu, Xiu; Li, Chenyang; Li, Yushu; Sang, Miao; Shan, Zhongyan; Teng, Weiping; Guan, Haixia

    2014-11-01

    The purpose of the study is to explore the roles of leptin and interleukin-6 (IL-6) during the first postpartum year in the occurrence and development of postpartum thyroiditis (PPT). We retrospectively collected serum samples from 57 PPT patients consisting of 34 overt PPT (O-PPT) and 23 subclinical PPT (S-PPT) in addition to 37 healthy postpartum women at four postpartum time points, i.e., 3-day and 3, 6, 12-month postpartum. Serum leptin and IL-6 levels were measured by radioimmunoassay and ELISA assay, respectively. Leptin level and leptin/BMI (LEP/BMI) ratio were higher in PPT patients than in control during the first postpartum year, but were not significantly different between O-PPT and S-PPT. However, a similar trend but did not reach significant difference in IL-6 level was observed during the postpartum period in PPT patients and control women. We conclude that a sustained high level of serum leptin after delivery may be involved in the pathogenesis of PPT. IL-6 does not contribute to the development of PPT. PMID:24573491

  11. Serum Leptin Levels in Polycystic Ovary Syndrome and Its Relationship with Metabolic and Hormonal Profile in Pakistani Females

    PubMed Central

    Rehman, Rehana; Tariq, Saba

    2014-01-01

    The study aimed to investigate the levels of serum leptin in PCOS females and to correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety normal cycling (NC) females with matched age and body mass index (BMI) were recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free testosterone, progesterone, thyroid profile, and FBG levels were measured. The mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL ± 1.49 vs 41.78 ± 1.31 ng/mL, P > 0.05); however, leptin levels showed a strong correlation with BMI in PCOS and NC group (r = 0.77, P < 0.0001; r = 0.82, P < 0.0001, resp.). High E2 levels in NC had a significant correlation with leptin whereas FBG correlated with leptin in PCOS (r = 0.51, P = 0.005). TSH had a substantial correlation (r = 0.49, P < 0.005; r = 0.69, P < 0.005) in PCOS and NC, respectively. There was no significant difference found in circulating leptin concentration between PCOS and NC subjects. Leptin levels in PCOS were related with metabolic impairments manifested by disturbance in FBG levels and impairment of reproductive functions in terms of reduced E2 secretion. PMID:25587271

  12. Right hippocampus size is negatively correlated with leptin serum levels in bipolar disorder.

    PubMed

    Vianna-Sulzbach, Miréia; Rocha, Natalia P; Teixeira, Antonio Lucio; Rosa, Eduarda D; Goldani, André A S; Kauer-Sant Anna, Marcia; Gama, Clarissa S

    2015-12-15

    Obesity is more frequent in bipolar disorder. Adipokines are associated with depression and obesity via the inflammatory process. Twenty-six DSM-IV patients with BD and 39 controls were enrolled to assess the relationship between serum leptin and adiponectin with hippocampal volumes. Among patients, there was a significant negative correlation between right hippocampal volume and serum leptin levels. This result sum for the hypothesis of a pro-inflammatory state associated with BD and the prevalent co-morbid obesity. PMID:26434408

  13. Teaching at higher levels

    NASA Astrophysics Data System (ADS)

    1998-11-01

    Undergraduate physics programmes for the 21st century were under discussion at a recent event held in Arlington, USA, open to two or three members of the physics faculties of universities from across the whole country. The conference was organized by the American Association of Physics Teachers with co-sponsorship from the American Institute of Physics, the American Physical Society and Project Kaleidoscope. Among the various aims were to learn about physics departments that have successfully revitalized their undergraduate physics programmes with innovative introductory physics courses and multi-track majors programmes. Engineers and life scientists were to be asked directly how physics programmes can better serve their students, and business leaders would be speaking on how physics departments can help to prepare their students for the diverse careers that they will eventually follow. It was planned to highlight ways that departments could fulfil their responsibilities towards trainee teachers, to identify the resources needed for revitalizing a department's programme, and to develop guidelines and recommendations for a funding programme to support collaborative efforts among physics departments for carrying out the enhancements required. More details about the conference can be found on the AAPT website (see http://www.aapt.org/programs/rupc.html). Meanwhile the UK's Higher Education Funding Council has proposed a two-pronged approach to the promotion of high quality teaching and learning, as well as widening participation in higher education from 1999-2000. A total of £60m should be available to support these initiatives by the year 2001-2002. As part of this scheme the Council will invite bids from institutions to support individual academics in enhancing learning and teaching, as well as in recognition of individual excellence. As with research grants, such awards would enable staff to pursue activities such as the development of teaching materials

  14. Leptin and Hunger Levels in Young Healthy Adults After One Night of Sleep Loss

    PubMed Central

    Pejovic, Slobodanka; Vgontzas, Alexandros N.; Basta, Maria; Tsaoussoglou, Marina; Zoumakis, Emanuel; Vgontzas, Angeliki; Bixler, Edward O.; Chrousos, George P.

    2013-01-01

    Summary Short-term sleep curtailment associated with activation of the stress system in healthy, young adults has been shown to be associated with decreased leptin levels, impaired insulin sensitivity and increased hunger and appetite. To assess the effects of one night of sleep loss in a less stressful environment on hunger, leptin, adiponectin, cortisol, and blood pressure/heart rate and whether a 2-hour mid-afternoon nap reverses the changes associated with sleep loss, 21 young healthy individuals (10 men, 11 women) participated in a 7-day sleep deprivation experiment (4 consecutive nights followed by a night of sleep loss and 2 recovery nights). Half of the subjects were randomly assigned to take a mid-afternoon nap (1400–1600) the day following the night of total sleep loss. Serial 24-hour blood sampling and hunger scales were completed on the fourth (pre-deprivation) and sixth day (post-deprivation). Leptin levels were significantly increased after one night of total sleep loss, whereas adiponectin, cortisol levels, blood pressure/heart rate, and hunger were not affected. Daytime napping did not influence the effects of sleep loss on leptin, adiponectin or hunger. Acute sleep loss, in a less stressful environment, influences leptin levels in an opposite manner from that of short-term sleep curtailment associated with activation of the stress system. It appears that sleep loss associated with activation of the stress system but not sleep loss per se may lead to increased hunger and appetite and hormonal changes which ultimately may lead to increased consumption of “comfort” food and obesity. PMID:20545838

  15. Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans

    PubMed Central

    Snyder, Eric M.; Carr, Richard D.; Deacon, Carolyn F.; Johnson, Bruce D.

    2009-01-01

    Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 ± 0.8 pg·mL−1; hypoxia, 7.7 ± 1.5 pg·mL−1; p < 0.05; range, −16% to 190%), no change in the average GLP-1 response to hypoxia, and only a small trend toward an increase in GLP-1 levels 40 min postmeal (fasting, 15.7 ± 0.9 vs 15.9 ± 0.7 pmol·L−1; 20 min postmeal, 21.7 ± 0.9 vs 21.8 ± 1.2 pmol·L−1; 40 min postmeal, 19.5 ± 1.2 vs. 21.0 ± 1.2 pmol·L−1 for normoxia and hypoxia, respectively; p > 0.05 normoxia vs hypoxia). There was a correlation between SaO2 and leptin after the 17 h exposure (r= 0.45; p < 0.05), but no relation between SaO2 and GLP-1. These data confirm that leptin increases with hypoxic exposure in humans. Further study is needed to determine the influence of hypoxia and altitude on GLP-1 levels. PMID:18923568

  16. Leptin resistance is not the primary cause of weight gain associated with reduced sex hormone levels in female mice.

    PubMed

    da Silva, Regina P; Zampieri, Thais T; Pedroso, João A B; Nagaishi, Vanessa S; Ramos-Lobo, Angela M; Furigo, Isadora C; Câmara, Niels O; Frazão, Renata; Donato, Jose

    2014-11-01

    Several studies have shown that estrogens mimic leptin's effects on energy balance regulation. However, the findings regarding the consequences of reduced sex hormone levels on leptin sensitivity are divergent. In the present study, we employed different experimental paradigms to elucidate the interaction between estrogens, leptin, and energy balance regulation. We confirmed previous reports showing that ovariectomy caused a reduction in locomotor activity and energy expenditure leading mice to obesity and glucose intolerance. However, the acute and chronic anorexigenic effects of leptin were preserved in ovariectomized (OVX) mice despite their increased serum leptin levels. We studied hypothalamic gene expression at different time points after ovariectomy and observed that changes in the expression of genes involved in leptin resistance (suppressors of cytokine signaling and protein-tyrosine phosphatases) did not precede the early onset of obesity in OVX mice. On the contrary, reduced sex hormone levels caused an up-regulation of the long form of the leptin receptor (LepR), resulting in increased activation of leptin signaling pathways in OVX leptin-treated animals. The up-regulation of the LepR was observed in long-term OVX mice (30 d or 24 wk after ovariectomy) but not 7 days after the surgery. In addition, we observed a progressive decrease in the coexpression of LepR and estrogen receptor-α in the hypothalamus after the ovariectomy, resulting in a low percentage of dual-labeled cells in OVX mice. Taken together, our findings suggest that the weight gain caused by reduced sex hormone levels is not primarily caused by induction of a leptin-resistance state. PMID:25144922

  17. Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort.

    PubMed

    Gossai, Anala; Lesseur, Corina; Farzan, Shohreh; Marsit, Carmen; Karagas, Margaret R; Gilbert-Diamond, Diane

    2015-01-01

    Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs+MMA+DMA) was associated with a 10.3% (95% CI: 0.8-20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: -1.0-18.6%) and 10.3% (95% CI: 1.2-20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: -3.4-17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth. PMID:25460635

  18. Leptin's metabolic and immune functions can be uncoupled at the ligand/receptor interaction level.

    PubMed

    Zabeau, Lennart; Jensen, Cathy J; Seeuws, Sylvie; Venken, Koen; Verhee, Annick; Catteeuw, Dominiek; van Loo, Geert; Chen, Hui; Walder, Ken; Hollis, Jacob; Foote, Simon; Morris, Margaret J; Van der Heyden, José; Peelman, Frank; Oldfield, Brian J; Rubio, Justin P; Elewaut, Dirk; Tavernier, Jan

    2015-02-01

    The adipocyte-derived cytokine leptin acts as a metabolic switch, connecting the body's metabolism to high-energy consuming processes such as reproduction and immune responses. We here provide genetic and biochemical evidence that the metabolic and immune functions of leptin can be uncoupled at the receptor level. First, homozygous mutant fatt/fatt mice carry a spontaneous splice mutation causing deletion of the leptin receptor (LR) immunoglobulin-like domain (IGD) in all LR isoforms. These mice are hyperphagic and morbidly obese, but display only minimal changes in size and cellularity of the thymus, and cellular immune responses are unaffected. These animals also displayed liver damage in response to concavalin A comparable to wild-type and heterozygous littermates. Second, treatment of healthy mice with a neutralizing nanobody targeting IGD induced weight gain and hyperinsulinaemia, but completely failed to block development of experimentally induced autoimmune diseases. These data indicate that leptin receptor deficiency or antagonism profoundly affects metabolism, with little concomitant effects on immune functions. PMID:25098352

  19. Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients

    PubMed Central

    Ayvaz, Havva Hilal; Ozturk, Gulfer; Ergin, Can; Akıs, Havva Kaya; Gonul, Muzeyyen; Arzuhal, Ercan

    2016-01-01

    Introduction Isotretinoin has been successfully used for the treatment of acne vulgaris. Aim To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Material and methods Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5–0.6 mg/kg and raised to 0.6–0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. Results The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Conclusions Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels. PMID:27605902

  20. Effects and mechanisms of vitamin A and vitamin E on the levels of serum leptin and other related cytokines in rats with rheumatoid arthritis

    PubMed Central

    XIONG, RI-BO; LI, QING; WAN, WEI-REN; GUO, JIN-QIANG; LUO, BING-DE; GAN, LU

    2014-01-01

    Leptin has been identified as an important cytokine in the inflammatory networks of rheumatoid arthritis (RA). Higher serum leptin levels may accelerate the development of RA. This study aimed to examine the effects of vitamin A (VitA) and vitamin E (VitE) on the levels of leptin and other related experimental and clinical indices, and to explore the mechanisms of these effects through the Janus kinase/signal transducer and activator of transcription (STAT) signal transduction pathway in rats with collagen-induced arthritis (CIA). CIA model rats were established by the intradermal injection of bovine type II collagen emulsified in incomplete Freund’s adjuvant, followed by a booster intradermal injection. Four weeks later, the CIA model rats were treated with 42.86 μg retinol equivalents/kg body weight (b.w.) VitA or 200 mg/kg b.w. VitE for four weeks. The levels of leptin, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, IL-4, C-reactive protein (CRP) and rheumatic factor were measured by ELISA using commercial kits, and the erythrocyte sedimentation rate (ESR) was determined. In addition, the expression levels of phosphorylated (p)-STAT1, p-STAT3 and leptin in the synovium were evaluated by western blot analysis. The results indicated that VitA and VitE significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR and significantly increased the levels of IL-10 compared with those of the model group. Furthermore, significantly reduced p-STAT3 protein expression levels were observed in the VitA and VitE groups. In conclusion, VitA and VitE reduced the levels of serum leptin protein and other cytokines. Furthermore, VitA and VitE also reduced the p-STAT3 protein levels. The present study may provide a novel approach for the treatment of RA. PMID:25009608

  1. Genetic variations of leptin and leptin receptor are associated with body composition changes in response to physical training.

    PubMed

    Huuskonen, Antti; Lappalainen, Jani; Tanskanen, Minna; Oksala, Niku; Kyröläinen, Heikki; Atalay, Mustafa

    2010-06-01

    Leptin regulates body weight, metabolism, and tissue adaptations to environmental stressors. We examined the association of single nucleotide polymorphism (SNP) of leptin promoter G-2548A (rs7799039) and leptin receptor Gln223Arg (rs1137101) with body composition, plasma leptin levels, and peak oxygen uptake (VO(2)peak) in response to 8 weeks of physical training in 48 male military conscripts. AA homozygotes of leptin promoter SNP-2548 showed higher body fat and BMI values than G allele carriers. Acute exercise decreased leptin levels in G allele carriers, but increased in AA homozygotes. Physical training significantly decreased BMI values and also a tendency for decreased plasma leptin levels was observed in all subjects. In G allele carriers, BMI loss was mainly due to decreased fat mass, whereas in AA homozygotes due to loss of fat-free mass. Training increased VO(2)peak in all subjects with most prominent effects in G allele carriers. Regarding leptin receptor SNP, there were no statistically significant differences in BMI values between the genotype groups at baseline or after physical training. Our results suggest that physical training-induced alterations in body composition and plasma leptin may be influenced by a genetic variation of leptin promoter but not of leptin receptor. PMID:20517895

  2. Leptin Levels and Nutritional Status of Indigenous Tepehuán and Mestizo Subjects in Durango, Mexico

    PubMed Central

    Delgadillo Guzmán, Dealmy; Marchat Marchau, Laurence Annie; Reyes, José L.; Loera Castañeda, Verónica; Sosa Macías, Martha; García Vivas, Jessica; Asseff, Ismael Lares

    2014-01-01

    The aim of this study was to assess differences in nutritional status and their association with circulating leptin levels in the indigenous Tepehuán people of Mezquital Durango and Mestizo populations of Durango City, Mexico. A group of 128 volunteers aged 18 through 59 years were recruited for the study: 60 indigenous Tepehuán from Mezquital and 68 Mestizo individuals from Durango City. The classification of nutritional status was through body mass index (BMI). Clinical evaluations, including anthropometry and lipid profiles, were performed to ascertain the health of the participants. Circulating leptin levels were determined in blood samples after at 08 hours of fasting. The healthy subjects were classified according to BMI: 32 Tepehuán and 30 Mestizo subjects were of normal weight (NW), and 28 Tepehuán and 38 Mestizo subjects were overweight or obese (OW/O). Both NW and OW/O Tepehuán subjects showed lower leptin concentrations than the comparable Mestizo subjects. Statistical analysis showed a negative Pearson's correlation (r = −0.5; P < 0.05) between BMI and leptin levels in NW Tepehuán subjects, but no significant correlation was found in other groups. The differences found in Tepehuán compared with Mestizo subjects might be explained by poor nutritional status, which leads to scarce adipose tissue and low levels of leptin synthesis. Leptin concentration and its relationship to BMI are associated with ethnicity. PMID:24825928

  3. Leptin levels and nutritional status of indigenous Tepehuán and Mestizo subjects in Durango, Mexico.

    PubMed

    Guzmán, Dealmy Delgadillo; Marchau, Laurence Annie Marchat; Reyes, José L; Castañeda, Verónica Loera; Macías, Martha Sosa; Vivas, Jessica García; Asseff, Ismael Lares

    2014-01-01

    The aim of this study was to assess differences in nutritional status and their association with circulating leptin levels in the indigenous Tepehuán people of Mezquital Durango and Mestizo populations of Durango City, Mexico. A group of 128 volunteers aged 18 through 59 years were recruited for the study: 60 indigenous Tepehuán from Mezquital and 68 Mestizo individuals from Durango City. The classification of nutritional status was through body mass index (BMI). Clinical evaluations, including anthropometry and lipid profiles, were performed to ascertain the health of the participants. Circulating leptin levels were determined in blood samples after at 08 hours of fasting. The healthy subjects were classified according to BMI: 32 Tepehuán and 30 Mestizo subjects were of normal weight (NW), and 28 Tepehuán and 38 Mestizo subjects were overweight or obese (OW/O). Both NW and OW/O Tepehuán subjects showed lower leptin concentrations than the comparable Mestizo subjects. Statistical analysis showed a negative Pearson's correlation (r = -0.5; P < 0.05) between BMI and leptin levels in NW Tepehuán subjects, but no significant correlation was found in other groups. The differences found in Tepehuán compared with Mestizo subjects might be explained by poor nutritional status, which leads to scarce adipose tissue and low levels of leptin synthesis. Leptin concentration and its relationship to BMI are associated with ethnicity. PMID:24825928

  4. Sex-specific chronic stress response at the level of adrenal gland modifies sexual hormone and leptin receptors

    PubMed Central

    Balog, Marta; Miljanović, Milan; Blažetić, Senka; Labak, Irena; Ivić, Vedrana; Viljetić, Barbara; Borbely, Attila; Papp, Zoltán; Blažeković, Robert; Vari, Sandor G.; Fagyas, Miklós; Heffer, Marija

    2015-01-01

    Aim To compare cardiometabolic risk-related biochemical markers and sexual hormone and leptin receptors in the adrenal gland of rat males, non-ovariectomized females (NON-OVX), and ovariectomized females (OVX) under chronic stress. Methods Forty six 16-week-old Sprague-Dawley rats were divided into male, NON-OVX, and OVX group and exposed to chronic stress or kept as controls. Weight, glucose tolerance test (GTT), serum concentration of glucose, and cholesterol were measured. Adrenal glands were collected at the age of 28 weeks and immunohistochemical staining against estrogen beta (ERβ), progesterone (PR), testosterone (AR), and leptin (Ob-R) receptors was performed. Results Body weight, GTT, serum cholesterol, and glucose changed in response to stress as expected and validated the applied stress protocol. Stressed males had significantly higher number of ERβ receptors in comparison to control group (P = 0.028). Stressed NON-OVX group had significantly decreased AR in comparison to control group (P = 0.007). The levels of PR did not change in any consistent pattern. The levels of Ob-R increased upon stress in all groups, but the significant difference was reached only in the case of stressed OVX group compared to control (P = 0.033). Conclusion Chronic stress response was sex specific. OVX females had similar biochemical parameters as males. Changes upon chronic stress in adrenal gland were related to a decrease in testosterone receptor in females and increase in estrogen receptor in males. PMID:25891869

  5. Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels.

    PubMed

    Sun, Qi; Cornelis, Marilyn C; Kraft, Peter; Qi, Lu; van Dam, Rob M; Girman, Cynthia J; Laurie, Cathy C; Mirel, Daniel B; Gong, Huizi; Sheu, Chau-Chyun; Christiani, David C; Hunter, David J; Mantzoros, Christos S; Hu, Frank B

    2010-05-01

    Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 x 10(-8)); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 x 10(-9), 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 x 10(-4)). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits. PMID:20167575

  6. Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels

    PubMed Central

    Sun, Qi; Cornelis, Marilyn C.; Kraft, Peter; Qi, Lu; van Dam, Rob M.; Girman, Cynthia J.; Laurie, Cathy C.; Mirel, Daniel B.; Gong, Huizi; Sheu, Chau-Chyun; Christiani, David C.; Hunter, David J.; Mantzoros, Christos S.; Hu, Frank B.

    2010-01-01

    Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 × 10−8); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 × 10−9, 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 × 10−4). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits. PMID:20167575

  7. Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue.

    PubMed

    Lee, Mi-Jeong; Wang, Yanxin; Ricci, Matthew R; Sullivan, Sean; Russell, Colleen D; Fried, Susan K

    2007-03-01

    Serum leptin levels are upregulated in proportion to body fat and also increase over the short term in response to meals or insulin. To understand the mechanisms involved, we assessed leptin synthesis and secretion in samples of adipose tissue from subjects with a wide range of BMI. Tissue leptin content and relative rates of leptin biosynthesis, as determined by metabolic labeling, were highly correlated with each other and with BMI and fat cell size. To understand mechanisms regulating leptin synthesis in obesity, we used biosynthetic labeling to directly assess the effects of insulin and glucocorticoids (dexamethasone) on leptin synthesis and secretion in human adipose tissue. Chronic treatment (1-2 days in organ culture) with insulin increased relative rates of leptin biosynthesis without affecting leptin mRNA levels. In contrast, dexamethasone increased leptin mRNA and biosynthesis in parallel. Acute treatment with insulin or dexamethasone (added during 1-h preincubation and 45-min pulse labeling) did not affect relative rates of leptin biosynthesis, but pulse-chase studies showed that addition of insulin nearly doubled the release of [35S]leptin after a 1-h chase. We conclude that the higher leptin stores in adipose tissue of obese humans are maintained by chronic effects of insulin and glucocorticoids acting at pre- and posttranslational levels and that the ability of insulin to increase the release of preformed leptin may contribute to short-term variations in circulating leptin levels. PMID:17122089

  8. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

    PubMed

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  9. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency

    PubMed Central

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    Backgrounds Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. Material/Methods A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. Results The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. Conclusions Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  10. Fish oil N-3 fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.

    PubMed

    Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-02-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  11. Fish Oil N-3 Fatty Acids Increase Adiponectin and Decrease Leptin Levels in Patients with Systemic Lupus Erythematosus

    PubMed Central

    Lozovoy, Marcell Alysson Batisti; Colado Simão, Andréa Name; Morimoto, Helena Kaminami; Scavuzzi, Bruna Miglioranza; Iriyoda, Tathiana Veiga Mayumi; Reiche, Edna Maria Vissoci; Cecchini, Rubens; Dichi, Isaias

    2015-01-01

    Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE. PMID:25690094

  12. Effect of zinc supplementation on body mass index and serum levels of zinc and leptin in pediatric hemodialysis patients

    PubMed Central

    El-Shazly, Ahmed Nabih; Ibrahim, Soha Abd El-Hady; El-Mashad, Ghada Mohamed; Sabry, Jehan H; Sherbini, Nashwa Said

    2015-01-01

    Introduction Zinc is an essential trace element for human nutrition, and its deficiency is associated with anorexia, poor food efficiency, growth retardation, and impaired neurological and immune systems. The zinc-deficiency rate is particularly high in many disease states, such as with end-stage renal disease patients undertaking hemodialysis. The aim of this study was to determine the effect of zinc supplementation on body mass index (BMI) and serum levels of zinc and leptin in pediatric hemodialysis patients. Patients and methods This was a prospective clinical trial study in which 60 hemodialysis patients were randomly divided into two groups: group I received 50–100 mg zinc sulfate (equivalent to 11–22 mg elemental zinc) according to age, sex, and nutritional status of the child; and group II received placebo (cornstarch) twice daily for 90 days. Anthropometric measurements were taken, and serum zinc and leptin levels were determined by colorimetric test with 5-Br-3′-phosphoadenosine-5′-phosphosulfate and enzyme-linked immunosorbent assay, respectively, at days 0 and 90 of the study. Results Zinc supplementation resulted in a significant increase in mean serum zinc level and BMI. Serum leptin decreased significantly after supplementation in children under hemodialysis. A significant negative correlation was observed between serum zinc and leptin levels as a result of zinc supplementation. Conclusion There was an increase in serum zinc level and BMI and decreased serum leptin after zinc supplementation in children under hemodialysis. PMID:26677341

  13. Association of Leptin with Body Pain in Women

    PubMed Central

    Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D.; Stefanick, Marcia L.

    2016-01-01

    Abstract Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

  14. Association of Leptin with Body Pain in Women.

    PubMed

    Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

    2016-07-01

    Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

  15. Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort.

    PubMed

    Shabana, -; Hasnain, Shahida

    2016-06-01

    Leptin is a protein hormone synthesized by adipocytes and is involved in the regulation of food intake and energy expenditure. We hypothesized that any change in the promoter sequence can affect the expression of the gene and hence leptin protein levels in the serum. The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a Pakistani cohort consisting of 250 obese and 225 non-obese control subjects. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured by standard methods and levels of fasting blood glucose (FBG), total cholesterol, triglycerides, HDLC, LDLC, and leptin were determined. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the LEP G-2548A polymorphism showed significant association with obesity in Pakistan. In addition, the polymorphism showed association with weight, height, BMI, WC, HDLC and serum leptin levels. The findings suggest that the leptin promoter G-2548A variant may play its part in the progression to obesity by not only affecting the body's fat distribution but also by changing the serum leptin and HDLC levels. PMID:27240985

  16. Body composition variables and leptin levels in functional hypothalamic amenorrhea and amenorrhea related to eating disorders.

    PubMed

    Bruni, Vincenzina; Dei, Metella; Morelli, Chiara; Schettino, M Teresa; Balzi, Daniela; Nuvolone, Daniela

    2011-12-01

    The purpose of the study was to identify diagnostic criteria that can distinguish between subjects with functional hypothalamic amenorrhea largely related to minimal energy deficiency and those in whom failure of adaptive response to stress prevails. We studied 59 young women with secondary amenorrhea related to modest eating disorders and 58 who complained of stressful events in their history. We assessed anthropometric measurements, body composition using dual energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA), and basal endocrine profile. Subjects with disordered eating had lower body mass index (BMI), fat mass (FM) measured with both techniques, lumbar mineral density and direct and indirect measures of lean mass. Leptin and free tri-iodothyronine(FT(3)) concentrations also proved lower in the group of subjects with eating disorders, although there was no significant difference in cortisol between the two groups. Leptin levels were positively associated not only with fat mass, but also with body cell mass indexed to height and phase angle, parameters studied with BIA as expression of active lean compartment. A multivariate model confirmed the utility of integrating endocrine data with the study of body composition. The use of bioelectrical impedance analysis proved to be, in clinical use, a valid diagnostic alternative to DEXA, especially considering body cell mass and phase angle. PMID:21906977

  17. Leptin and pregnancy outcome.

    PubMed

    Kratzsch, J; Höckel, M; Kiess, W

    2000-12-01

    Leptin, a recently discovered hormone that is involved in the regulation of body weight, appears to be one of the hormonal factors that signal the body's readiness for sexual maturation and reproduction to the brain. The present review focuses on clinical and experimental studies that describe the roles of maternal and foetal leptin as predictive factors for the physiological and pathophysiological development of the foetus during pregnancy, assisted reproduction and neonatal life. Through evaluating alterations of maternal serum leptin levels, a physiological hyperleptinaemia has been observed to occur, particularly during the second and third trimesters of pregnancy, which is not associated with a decreased food intake or reduced metabolic activity in the pregnant women. This state of leptin resistance is comparable to the condition in obesity. In contrast, hypoleptinaemia is suggested to be an indicator for the cessation of pregnancy, either naturally at term or as a result of pathology at any time during gestation. Thus, an appropriate maternal leptin level seems to be a prerequisite for a normal pregnancy. The main source of foetal leptin is the still immature foetal adipose tissue. As intrauterine growth has been found to be independently associated with cord blood leptin level, it has been suggested that leptin plays a role as a regulator of foetal growth. During assisted reproduction cycles leptin levels in the follicular fluid of patients may be also of predictive value, with low levels predicting therapeutic failure. Finally, the relevance of leptin to postnatal development is reviewed; leptin may be important for regulation of satiety and peripheral metabolism. In summary, leptin appears to be an important permissive factor that is involved in female reproduction. PMID:11128413

  18. The Relationship between -2548 G/A Leptin Gene Polymorphism and Risk of Breast Cancer and Serum Leptin Levels in Ahvazian Women

    PubMed Central

    Mohammadzadeh, Ghorban; Ghaffari, Mohammad-Ali; Bafandeh, Ahmmad; Hosseini, Seyed-Mohammad; Ahmadi, Behnaz

    2015-01-01

    Background Potential association of leptin (LEP) gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. We investigated whether genetic variations in the LEP -2548G/A gene are associated with risk of breast cancer. Methods This case-control study consisted of 100 breast cancer cases and 100 control subjects without breast cancer that matched for age and body mass index (BMI). Genotyping of LEP -2548G/A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Serum leptin level was determined by ELISA in all study subjects. Results The genotype distributions (AA, AG, and GG) were 36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group, respectively. The frequency of LEP -2548 GG genotype was significantly elevated in breast cancer cases as compared to controls (χ2=6.90, p=0.032). Similar difference was also found in allele frequencies between two groups (χ2=5.65, p=0.017). A markedly increase risk of breast cancer was associated with the LEP -2548GG genotype when compared to the LEP -2548 AA genotype (OR=4.33, 95% CI=1.09-17.22). In addition, postmenopausal women who bear at least one LEP -2548 G allele were at a markedly increased risk of breast cancer after adjusting for age and BMI confounders (OR=12.24, 95% CI=1.13-131.73). Conclusion The LEP -2548 G/A polymorphism is associated with markedly increased risk of breast cancer especially in postmenopausal Ahvazian women and supported the hypothesis that leptin is involved in breast cancer. PMID:25960849

  19. Consumption of sugar-sweetened beverages is positively related to insulin resistance and higher plasma leptin concentrations in men and nonoverweight women.

    PubMed

    Lana, Alberto; Rodríguez-Artalejo, Fernando; Lopez-Garcia, Esther

    2014-07-01

    The mechanisms for the association of the consumption of sugar-sweetened beverages (SSBs) with obesity and type 2 diabetes are only partly understood. The objective of the study was to examine the association of habitual SSB consumption with biomarkers of energy metabolism, including serum glucose, glycated hemoglobin, insulin, insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)], and leptin. Data were taken from the Study on Nutrition and Cardiovascular Risk in Spain (ENRICA), a cross-sectional study conducted during 2008-2010 in 7842 individuals representative of the population of Spain aged 18-59 y. Diet was assessed with a validated computerized diet history. Biomarkers were determined in 12-h fasting blood samples. Analyses were performed with linear regression with adjustment for the main confounders, including body mass index (BMI), waist circumference, and morbidity. In men, a 1-serving (200 mL)/d increase in the consumption of SSBs was associated with higher plasma concentrations of insulin (2.14%, P = 0.01), higher HOMA-IR (1.90%, P = 0.04), and higher concentrations of leptin (2.73%, P = 0.01). Among women, these associations were found only in those with a BMI <25 kg/m² (insulin: 2.88%, P = 0.004; HOMA-IR: 3.03%, P = 0.01; and leptin: 4.57%, P = 0.01) or with a waist circumference <80 cm (insulin: 2.79%, P = 0.01; HOMA-IR: 3.00%, P = 0.01; and leptin: 3.63%, P = 0.05). In conclusion, the consumption of SSBs was associated with higher concentrations of insulin and leptin and a higher HOMA-IR in men and in nonoverweight women. Insulin resistance and higher leptin may be early markers of metabolic dysfunction associated with SSBs. PMID:24828025

  20. Two isoforms of leptin in the White-clouds Mountain minnow (Tanichthys albonubes): Differential regulation by estrogen despite similar response to fasting.

    PubMed

    Chen, Ting; Chen, Shuang; Ren, Chunhua; Hu, Chaoqun; Tang, Dongsheng; Yan, Aifen

    2016-01-01

    Leptin has been well-established as a canonical anorexic peptide hormone in mammals, though much of its function in fish remains obscure. In this study, the cDNAs of two leptin isoforms (leptin-A and leptin-B) were cloned from the liver of a small cyprinid fish, Tanichthys albonubes. The two T. albonubes leptins, sharing low primary amino acid sequence homology with their mammalian counterparts, and between themselves, are highly conserved in three-dimensional protein structures and gene structures. Liver is a major source of leptin mRNA in T. albonubes with leptin-A being the dominant form. The expression of hepatic leptin-A but not leptin-B mRNA in female fish is significantly higher than in male fish. Transcriptional hepatic levels of leptin-A and leptin-B in both male and female fish were demonstrated to increase after long-term fasting (10-25days) but decline upon re-feeding (3days). Strikingly, estrogen (E2) administration induced only leptin-A but not leptin-B hepatic mRNA expression in both male and female fish. Our study here provides the first evidence for differential regulation of two leptins in fish, and sheds new light on the possible origin of leptin in lower vertebrates. PMID:26386182

  1. Anticontractile Effect of Perivascular Adipose Tissue and Leptin are Reduced in Hypertension

    PubMed Central

    Gálvez-Prieto, Beatriz; Somoza, Beatriz; Gil-Ortega, Marta; García-Prieto, Concha F.; de las Heras, Ana I.; González, M. Carmen; Arribas, Silvia; Aranguez, Isabel; Bolbrinker, Juliane; Kreutz, Reinhold; Ruiz-Gayo, Mariano; Fernández-Alfonso, Maria S.

    2012-01-01

    Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10−9 M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase. PMID:22679436

  2. Interleukin-17 and leptin genes polymorphisms and their levels in relation to recurrent pregnancy loss in Egyptian females.

    PubMed

    Zidan, Haidy E; Rezk, Noha A; Alnemr, Amr Abd Almohsen; Moniem, Mohamed I Abdel

    2015-11-01

    Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A (rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women’s serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one. PMID:26467330

  3. Exercise-Associated Amenorrhea: Are Altered Leptin Levels an Early Warning Sign?

    ERIC Educational Resources Information Center

    Warren, Michelle P.; Ramos, Russalind H.; Bronson, Emily M.

    2002-01-01

    Although the exact cause of the female athlete triad (amenorrhea, disordered eating, and osteoporosis) is unknown, recent research implicates leptin, a hormone secreted by adipocytes. Leptin may be an important indicator of nutritional status and may play a role in reproductive function. Physicians who develop a plan for early recognition and…

  4. Serum leptin concentrations, leptin mRNA expression, and food intake during the estrous cycle in rats.

    PubMed

    Fungfuang, Wirasak; Nakada, Tomoaki; Nakao, Nobuhiro; Terada, Misao; Yokosuka, Makoto; Gizurarson, Sveinbjorn; Hau, Jann; Moon, Changjong; Saito, Toru R

    2013-03-01

    The aim of this study was to investigate food intake, serum leptin levels, and leptin mRNA expression during the sexual cycle in rats. Female Wistar-Imamichi rats aged 8-10 weeks were used in this experiment. Food intake was measured during the light and dark phases (light on at 07:00 and off at 19:00) of the 4-day estrous cycle in female rats. Serum leptin levels were measured by ELISA, and leptin mRNA expression levels were analyzed using real-time PCR on diestrous- and proestrous-stage rats. Our results revealed that during the sexual cycle, food intake was significantly higher in the dark phase compared with the light phase. Food intake in proestrous females was significantly lower in the light and dark phases compared with the other groups. Serum leptin concentrations were significantly higher in both phases in proestrous rats compared with diestrous rats. There was a significant increase in leptin mRNA expression in adipose tissue during the proestrous period compared with the diestrous period. These findings suggest that increased leptin mRNA expression and serum leptin levels, which are induced by estrogen during the proestrous stage, may play a role in regulating appetitive behavior. PMID:23573101

  5. Plasma leptin values in postmenopausal women with osteoporosis.

    PubMed

    Kocyigit, Hikmet; Bal, Serpil; Atay, Ayşenur; Koseoglu, Mehmet; Gurgan, Alev

    2013-08-01

    Obesity has a protective effect against osteoporosis and this effect has been attributed to a high body fat content. It has been shown that the leptin concentration is higher in obese patients. Leptin, the protein product of obesity gene, is a hormone produced in adipose tissue. Some studies suggest that endogenous leptin might influence bone metabolism in postmenopausal women. In this study, we investigated plasma leptin concentrations in postmenopausal women with osteoporosis and also analyzed the relationship between plasma leptin levels and bone mineral density (BMD) in order to understand the potential role of leptin in maintaining bone mass. Forty-two postmenopausal women with osteoporosis and thirty seven age and BMI-matched healthy postmenopausal women were included in the study. The mean femoral neck BMD value in the patient group was significantly lower than that in the control group (0.691±0.1 g/cm2 and 0.863±0.1 g/cm2, respectively; p<0.001). The mean plasma leptin concentration in the patient group was not significantly different from that in the control group (p>0.05). Plasma leptin levels were correlated with BMI in both groups (p<0.001 in the patient group and p=0.001 in controls). There was also a strong positive correlation between plasma leptin levels and %fat in both groups (p<0.001 in the patient group and p<0.001 in controls). But there was no correlation between plasma leptin levels and femoral neck BMD values in both groups. Our results do not support the hypothesis that leptin itself plays an important role in maintaining bone mass in postmenopausal women. PMID:23988172

  6. Adiponectin and leptin levels in HIV-infected subjects with insulin resistance and body fat redistribution.

    PubMed

    Mynarcik, Dennis C; Combs, Terry; McNurlan, Margaret A; Scherer, Philipp E; Komaroff, Eugene; Gelato, Marie C

    2002-12-15

    In this study, we sought to determine the relationship between serum levels of leptin and adiponectin (Acrp30) in patients with HIV-associated lipodystrophy (HIV-LD). Three groups of subjects were studied; HIV-positive subjects with lipodystrophy (HIV-LD; n = 22), HIV-positive subjects without lipodystrophy (HIV; n = 17), and ethnicity- and body mass index-matched healthy control subjects (n = 20). Although total body fat from dual energy x-ray absorptiometry was similar in all three groups, the HIV-LD group had a significantly lower mean proportion of body fat in the limbs +/- SEM (37.2% +/- 2.2%) than either controls (49.8% +/- 1.5%) or HIV subjects (45.7% +/- 2.0%). The HIV-LD group also had the lowest mean insulin sensitivity +/- SEM (5.11 +/- 0.59 mg of glucose/[kg of lean body mass. min] vs. 10.2 +/- 0.72 mg of glucose/[kg of lean body mass. min] in controls and 8.64 +/- 0.69 mg of glucose/[kg of lean body mass. min] in the HIV group). Leptin levels were similar in all three groups and were significantly correlated to total body fat (r = 0.86; p <.001), but these levels did not correlate with either insulin sensitivity or limb fat. Mean Acrp30 levels +/- SEM were lowest in the HIV-LD group (5.43 +/- 0.44 microg/mL vs. 11.2 +/- 1.4 microg/mL in the HIV group and 14.9 +/- 1.8 microg/mL in control subjects). Further, Acrp30 levels were positively correlated with insulin sensitivity (r = 0.610; p <.001) and limb fat (r = 0.483; p <.001). However, the correlation between limb fat and insulin sensitivity disappeared when Acrp30 level and other potential mediators were removed from the association, suggesting that a deficiency in Acrp30 in subjects with HIV-LD may be part of the mechanism for the reduced insulin sensitivity. PMID:12473840

  7. Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

    PubMed Central

    Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

    2013-01-01

    Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, −40.1%, p<0.0001; diet, −27.1%, p<0.0001; exercise, −12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID

  8. The Relationship Between Serum Adiponectin, Tumor Necrosis Factor−Alpha, Leptin Levels and Insulin Sensitivity in Childhood and Adolescent Obesity: Adiponectin is a Marker of Metabolic Syndrome

    PubMed Central

    Gönç, E. Nazlı; Özön, Z. Alev; Şen, Yaşar; Kandemir, Nurgün

    2009-01-01

    Objective: This study aimed (a) to investigate the relationship between the degree of obesity and serum adiponectin, tumor necrosis factor (TNF)−α, leptin, insulin levels and the lipid profile; (b) to clarify the relationship between insulin resistance/glucose tolerance and adipocytokine levels; and (c) to investigate the value of adipocytokine levels as a marker of metabolic syndrome (MS). Methods: We studied 151 obese children and adolescents (86 boys and 65 girls; mean age was 12.3±2.4 years). We defined obesity as a body−mass index (BMI) z−score more than 2 SD above the mean for age and sex. The control group consisted of 100 children (48 boys, 52 girls, mean age 12.4±2.5 years). Fasting glucose, insulin levels and lipid profiles were measured in all cases and controls after a 12−hour fast. Adiponectin, TNF−α, and leptin levels were measured in the subjects who participated in the adipocytokine branch of the study. An oral glucose tolerance test (OGTT) was also performed in all obese patients. Obese patients were grouped into three subgroups according to their glucose tolerance and insulin sensitivity assessment, and also according to whether they were grouped as MS or not. Results: Serum levels of total cholesterol, LDL and VLDL cholesterol, log triglyceride, insulin, leptin and TNF−α were higher, whereas HDL and square root adiponectin levels were lower in the obese group when compared with controls. Multiple regression analysis among BMI−z score, LDL, triglyceride, HOMA−IR, leptin and TNF−α as determinants of adiponectin revealed that BMI−z score was the only determinant for adiponectin (r:−0.45, p<0.0001). Adiponectin levels in hyperinsulinemic and impaired glucose tolerance groups (IGT) tended to be lower than in normoinsulinemic obese children, however, the difference was not significant. There was a weak negative correlation between adiponectin levels and increasing severity of insulin resistance (r=−0.23, p=0.005) in the

  9. Association of the physical activity with leptin blood serum level, body mass indices and obesity in schoolgirls.

    PubMed

    Plonka, Malgorzata; Toton-Morys, A; Adamski, P; Suder, A; Bielanski, W; Dobrzanska, M J; Kaminska, A; Piorecka, B; Glodzik, J

    2011-12-01

    Decreased physical activity is undoubtedly significantly associated with obesity. Similarly, the proper hormones secretion, the proper weight and body development. The aim of this study was to investigate the relationship between body mass composition and leptin concentration in relation to the degree of physical activity expressed in MET-h/week (metabolic equivalent per week). The study included 59 girls, aged 9-16 years (12.55±1.67) and divided into two groups: 1) PA: a physically active group of 29 girls and 2) PI: a group of 30 physically inactive girls. In all, physical activity was assessed using modified questionnaire concerning "activity for adolescents" and expressed in MET-h/week. Serum blood leptin concentrations in fasting girls were determined by RIA. Anthropometric parameters were measured and fatness indices calculated (BMI, SF, WHtR). Body composition (%BF, FM, FFM) was assessed using bioelectrical impedance analysis method (BIA). Statistical analysis showed significant differences between groups of PA and PI concerning values of BMI, WHtR, %BF, WC and MET-h/week as well as in leptin concentrations. In both groups of girls negative correlations between physical activity measured in MET and leptin concentrations and in WHtR were observed. The concentration of leptin was directly proportional to the degree of body fat and to the body composition expressed by BMI, WHtR, log SF, WC and %BF, FM and FFM, respectively. Increased physical activity was associated with lower body fat ratios and WHtR, BMI, WC, %BF, but did not affect significantly the changes in the values of log SF, FM and FFM. Higher values of BMI, WHtR and WC can provide not only a greater risk of obesity in general, but also cause excessive accumulation of fat in the central part of the body (abdominal obesity). PMID:22314567

  10. Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy.

    PubMed

    Kassai, Andrea; Muniyappa, Ranganath; Levenson, Amy E; Walter, Mary F; Abel, Brent S; Ring, Michael; Taylor, Simeon I; Biddinger, Sudha B; Skarulis, Monica C; Gorden, Phillip; Brown, Rebecca J

    2016-04-01

    Patients with lipodystrophy had elevated apolipoprotein CIII (apoCIII) compared to healthy controls. ApoCIII did not change with leptin treatment despite significant reductions in serum triglyceride. PMID:26900642

  11. Danger: Work on Higher Levels.

    ERIC Educational Resources Information Center

    Lapointe, Archie E.

    The Assessment Policy Committee of the National Assessment of Educational Progress (NAEP) has directed the NAEP staff to focus the 1985-86 Assessments of Reading, Mathematics, Science, and Computer Competence on the higher-order skills. Each Learning Area Committee worked independently developing three-dimensional models. These defined what could…

  12. Effect of exogenous leptin on serum levels of lipids, glucose, renal and hepatic variables in both genders of obese and streptozotocin-induced diabetic rats

    PubMed Central

    Hayatdavoudi, Parichehr; Ghasemi, Mohsen; Zendehbad, Bamdad; Soukhtanloo, Mohammad; Golshan, Alireza; Hadjzadeh, Mousa Al-Reza

    2015-01-01

    Objective(s): Leptin exerts various effects on appetite and body weight. Disruption of the obesity gene is precedent to fatness. Insulin or glucose elevates leptin, but streptozotocin reduces it. However, controversial data exist for the effects of leptin on diabetes and leptin level in each gender. Leptin can damage the kidney function but little evidence exists for its hepatic effects. The aim of this study was to investigate the probable sex-dependent differences in blood sugar levels, lipid profile, and renal and hepatic biochemical factors in the obesity and streptozotocin-induced diabetic rats after leptin administration. Materials and Methods: Wistar rats of both sexes were randomly divided into two groups, namely obese and diabetic rats. Each group was further divided into male and female subgroups. Extra fat and carbohydrate was added to the diet to induce obesity. Furthermore, streptozotocin (55 mg/kg, IP) was injected to induce diabetes. The treatment groups received leptin (0.1 mg/kg SC) for 10 days, and then, blood samples were taken from the orbital sinus for laboratory evaluations. Results: Leptin resulted in a significant weight loss in both sexes (P<0.001), food intake reduction in male rats (P<0.05), LDL reduction in female rats (obese (P<0.05) and diabetic (P<0.001)), and glucose level decline in the female diabetic rats (P<0.001). However, total protein concentration, LFT (liver function tests), urea and creatinin concentrations among different groups did not show any significant changes. Conclusion: Leptin caused some discrepant results, especially regarding the LDL and glucose levels in diabetic female rats. PMID:26949493

  13. Creation and Preliminary Characterization of a Leptin Knockout Rat

    PubMed Central

    Vaira, Sergio; Yang, Chang; McCoy, Aaron; Keys, Kelly; Xue, Shurong; Weinstein, Edward J.; Novack, Deborah V.

    2012-01-01

    Leptin, a cytokine-like hormone secreted mainly by adipocytes, regulates various pathways centered on food intake and energy expenditure, including insulin sensitivity, fertility, immune system, and bone metabolism. Here, using zinc finger nuclease technology, we created the first leptin knockout rat. Homozygous leptin null rats are obese with significantly higher serum cholesterol, triglyceride, and insulin levels than wild-type controls. Neither gender produced offspring despite of repeated attempts. The leptin knockout rats also have depressed immune system. In addition, examination by microcomputed tomography of the femurs of the leptin null rats shows a significant increase in both trabecular bone mineral density and bone volume of the femur compared with wild-type littermates. Our model should be useful for many different fields of studies, such as obesity, diabetes, and bone metabolism-related illnesses. PMID:22948215

  14. Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: A pilot study

    NASA Astrophysics Data System (ADS)

    Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi

    2012-09-01

    To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.

  15. Higher level twisted Zhu algebras

    SciTech Connect

    Ekeren, Jethro van

    2011-05-15

    The study of twisted representations of graded vertex algebras is important for understanding orbifold models in conformal field theory. In this paper, we consider the general setup of a vertex algebra V, graded by {Gamma}/Z for some subgroup {Gamma} of R containing Z, and with a Hamiltonian operator H having real (but not necessarily integer) eigenvalues. We construct the directed system of twisted level p Zhu algebras Zhu{sub p,{Gamma}}(V), and we prove the following theorems: For each p, there is a bijection between the irreducible Zhu{sub p,{Gamma}}(V)-modules and the irreducible {Gamma}-twisted positive energy V-modules, and V is ({Gamma}, H)-rational if and only if all its Zhu algebras Zhu{sub p,{Gamma}}(V) are finite dimensional and semisimple. The main novelty is the removal of the assumption of integer eigenvalues for H. We provide an explicit description of the level p Zhu algebras of a universal enveloping vertex algebra, in particular of the Virasoro vertex algebra Vir{sup c} and the universal affine Kac-Moody vertex algebra V{sup k}(g) at non-critical level. We also compute the inverse limits of these directed systems of algebras.

  16. Seasonal changes in body mass, serum leptin levels and hypothalamic neuropeptide gene expression in male Eothenomys olitor.

    PubMed

    Wan-long, Zhu; Zheng-kun, Wang

    2015-06-01

    The present study examined seasonal changes in body mass and energy metabolism in the Chaotung vole (Eothenomys olitor) and the physiological mechanisms underpinning these changes. Seasonal changes in the following parameters were measured in male E. olitor, body mass, food intake, thermogenesis, enzyme activity, masses of tissues and organs, hormone concentrations and expression of hypothalamic arcuate nucleus energy balance genes including neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin (POMC), and cocaine- and amphetamine-regulated transcript (CART). Body mass was constant over the year, but the masses of tissues and organs differed significantly between seasons. There were significant changes in body fat mass and serum leptin levels over the four seasons. E. olitor showed significant seasonal changes in food intake and thermogenesis, uncoupling protein 1 (UCP1) content, enzyme activity, and serum tri-iodothyronine (T3) and thyroxine (T4) levels. Moreover, mRNA expression in the hypothalamus showed significant seasonal changes. All of our results suggested that E. olitor had constant body mass over the year, which was inconsistent with the prediction of the 'set-point' hypothesis. However, body fat mass and serum leptin levels were significantly different among the four seasons, providing support for the 'set-point' hypothesis. The changes in leptin, NPY, AgRP, POMC, and CART mRNA levels may play a role in the regulation of energy intake in E. olitor. Furthermore, the role of leptin and hypothalamic neuropeptide gene in the regulation of energy metabolism and body mass may be different in animals that are acclimated to different seasons. PMID:25700741

  17. Leptin and Hormones: Energy Homeostasis.

    PubMed

    Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

    2016-09-01

    Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. PMID:27519135

  18. Leptin and endocrine parameters in marathon runners.

    PubMed

    Bobbert, T; Mai, K; Brechtel, L; Schulte, H M; Weger, B; Pfeiffer, A F H; Spranger, J; Diederich, S

    2012-03-01

    Endurance training may lead to different hormonal alterations e. g., exercised induced hypothalamic ovarian/testicular dysfunction. The aim of this study was to reveal new connections between physical exercise, leptin and hormonal responses. 36 male participants of the Berlin-Marathon had their blood samples taken 2 days before the marathon. Hormones of the hypothalamic-pituitary axis and leptin were correlated with the training status and the achieved marathon time. Leptin correlated with the achieved marathon time after being adjusted for age and BMI (r=0.607, p<0.001) and was lowest in the best trained runners. Additionally, when the group was divided into quartiles of their achieved marathon time, significantly increased cortisol, fT4, cortisol/DHEAS ratio and decreased IGF-1 levels were observed in the slowest group. In the better trained group, a decrease of testosterone/DHT ratio and an increase of testosterone/cortisol ratio were observed. Our study supports the thesis of a linear relationship between physical fitness and leptin variations in the physiological range. We found an increased anabolic hormonal response in well trained marathon runners and hormonal reactions of increased stress in less trained runners. As the stress-induced neuroendocrine adaptations in our study group are associated with more higher leptin values, the pathophysiological role of decreased leptin values seems to be limited to overtrained athletes. PMID:22261828

  19. Leptin levels in patients with anorexia nervosa following day/inpatient treatment do not predict weight 1 year post-referral.

    PubMed

    Seitz, Jochen; Bühren, Katharina; Biemann, Ronald; Timmesfeld, Nina; Dempfle, Astrid; Winter, Sibylle Maria; Egberts, Karin; Fleischhaker, Christian; Wewetzer, Christoph; Herpertz-Dahlmann, Beate; Hebebrand, Johannes; Föcker, Manuel

    2016-09-01

    Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN. PMID:26847072

  20. Fasting insulin levels influence plasma leptin levels independently from the contribution of adiposity: evidence from both a cross-sectional and an intervention study.

    PubMed

    Doucet, E; St-Pierre, S; Alméras, N; Mauriège, P; Després, J P; Richard, D; Bouchard, C; Tremblay, A

    2000-11-01

    The aim of the present investigation was to determine whether leptinemia is only a reflection of the status of fat stores or if insulinemia has a significant influence over leptin levels. Study 1 focused on the association between fasting plasma insulin and leptin in subjects of the Quebec Family Study who were first classified as either high- or low-insulin individuals and were then individually matched on the basis of fat mass (FM). In Study 2, 19 men and 23 women took part in a 15-week weight loss program that consisted of drug therapy (fenfluramine, 60 mg/day) or placebo coupled to an energy-restricted diet (-2930 kJ/day). Body weight, FM, and fat-free mass (assessed by underwater weighing) as well as visceral and sc abdominal and mid-thigh adipose tissue measured by computed tomography were assessed before and after weight loss. Blood samples were drawn and analyzed for fasting plasma insulin and leptin before and after weight loss. In Study 1, significant positive associations were noted between log10 transformed fasting insulin and leptin in both men (r = 0.55, P < 0.0001) and women (r = 0.48, P < 0.0001). Moreover, after having carefully matched high-insulin to low-insulin individuals on the basis of FM, significantly lower leptin levels were observed in the low-insulin groups, in men (5.5 vs. 8.1 ng/mL, P < 0.05) as well as in women (18.7 vs. 24 ng/mL, P < 0.05). Results from Study 2 showed significant reductions of body weight, FM, fat-free mass, visceral abdominal tissue, sc abdominal tissue, and mid-thigh adipose tissue levels in men and women in response to the weight loss protocol. Moreover, the decrease in fasting plasma insulin was the only significant correlate of changes in fasting plasma leptin levels during weight loss, even after corrections for changes in FM in both men (r = 0.50, P < 0.05) and women (r = 0.46, P < 0.05). These results suggest that in a population characterized by a wide range of adiposity hyperinsulinemia has the potential to

  1. Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women

    PubMed Central

    Kim, Mi-Hyun

    2015-01-01

    The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p < 0.01), body mass index (p < 0.001), percentage (%) of body fat (p < 0.001), and serum levels of leptin (p < 0.05), glucose (p < 0.001), and insulin (p < 0.01), than the non-vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p < 0.01) after adjustment for the % of body fat. A long-term vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women. PMID:26251836

  2. Comparative Study of Serum Leptin and Insulin Resistance Levels Between Korean Postmenopausal Vegetarian and Non-vegetarian Women.

    PubMed

    Kim, Mi-Hyun; Bae, Yun-Jung

    2015-07-01

    The present study was conducted to compare serum leptin and insulin resistance levels between Korean postmenopausal long-term semi-vegetarians and non-vegetarians. Subjects of this study belonged to either a group of postmenopausal vegetarian women (n = 54), who maintained a semi-vegetarian diet for over 20 years or a group of non-vegetarian controls. Anthropometric characteristics, serum leptin, serum glucose, serum insulin, insulin resistance (HOMA-IR; Homeostasis Model Assessment of Insulin Resistance), and nutrient intake were compared between the two groups. The vegetarians showed significantly lower body weight (p < 0.01), body mass index (p < 0.001), percentage (%) of body fat (p < 0.001), and serum levels of leptin (p < 0.05), glucose (p < 0.001), and insulin (p < 0.01), than the non-vegetarians. The HOMA-IR of the vegetarians was significantly lower than that of the non-vegetarians (p < 0.01) after adjustment for the % of body fat. A long-term vegetarian diet might be related to lower insulin resistance independent of the % of body fat in postmenopausal women. PMID:26251836

  3. Drug targeting of leptin resistance.

    PubMed

    Santoro, Anna; Mattace Raso, Giuseppina; Meli, Rosaria

    2015-11-01

    Leptin regulates glucose, lipid and energy homeostasis as well as feeding behavior, serving as a bridge between peripheral metabolically active tissues and the central nervous system (CNS). Indeed, this adipocyte-derived hormone, whose circulating levels mirror fat mass, not only exerts its anti-obesity effects mainly modulating the activity of specific hypothalamic neurons expressing the long form of the leptin receptor (Ob-Rb), but it also shows pleiotropic functions due to the activation of Ob-Rb in peripheral tissues. Nevertheless, several mechanisms have been suggested to mediate leptin resistance, including obesity-associated hyperleptinemia, impairment of leptin access to CNS and the reduction in Ob-Rb signal transduction effectiveness, among others. During the onset and progression of obesity, the dampening of leptin sensitivity often occurs, preventing the efficacy of leptin replacement therapy from overcoming obesity and/or its comorbidities. This review focuses on obesity-associated leptin resistance and the mechanisms underpinning this condition, to highlight the relevance of leptin sensitivity restoration as a useful therapeutic strategy to treat common obesity and its complications. Interestingly, although promising strategies to counteract leptin resistance have been proposed, these pharmacological approaches have shown limited efficacy or even relevant adverse effects in preclinical and clinical studies. Therefore, the numerous findings from this review clearly indicate a lack of a single and efficacious treatment for leptin resistance, highlighting the necessity to find new therapeutic tools to improve leptin sensitivity, especially in patients with most severe disease profiles. PMID:26071010

  4. Leptin: a potential novel antidepressant.

    PubMed

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-31

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  5. Leptin: A potential novel antidepressant

    PubMed Central

    Lu, Xin-Yun; Kim, Chung Sub; Frazer, Alan; Zhang, Wei

    2006-01-01

    Leptin, a hormone secreted from adipose tissue, was originally discovered to regulate body weight. The localization of the leptin receptor in limbic structures suggests a potential role for leptin in emotional processes. Here, we show that rats exposed to chronic unpredictable stress and chronic social defeat exhibit low leptin levels in plasma. Systemic leptin treatment reversed the hedonic-like deficit induced by chronic unpredictable stress and improved behavioral despair dose-dependently in the forced swim test (FST), a model widely used for screening potential antidepressant efficacy. The behavioral effects of leptin in the FST were accompanied by increased neuronal activation in limbic structures, particularly in the hippocampus. Intrahippocampal infusion of leptin produced a similar antidepressant-like effect in the FST as its systemic administration. By contrast, infusion of leptin into the hypothalamus decreased body weight but had no effect on FST behavior. These findings suggest that: (i) impaired leptin production and secretion may contribute to chronic stress-induced depression-like phenotypes, (ii) the hippocampus is a brain site mediating leptin's antidepressant-like activity, and (iii) elevating leptin signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID:16423896

  6. Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults

    PubMed Central

    2011-01-01

    Background Leptin is associated with cardiovascular disease (CVD); however, few studies have assessed its relationship with metabolic syndrome, especially in an Asian population. Therefore, the aim of the present study was to assess leptin levels and evaluate its association with CVD and metabolic syndrome. Methods In 2009, 957 subjects, who underwent a routine physical examination and choose leptin examination, were selected to participate. Participants (269 females and 688 males) were stratified according to leptin level quartiles. Metabolic syndrome was defined by NCEP ATP III using waist circumference cutoffs modified for Asian populations, and CVD risk was determined using the Framingham Heart Study profile. Results Leptin levels were correlated with CVD risk in men and women. With the exception of fasting plasma glucose, increased leptin levels were observed as factors associated with metabolic syndrome increased in both males and females. After adjusting for age, an association between leptin levels and metabolic syndrome was observed. After adjusting for age alone or with tobacco use, subjects in the highest leptin quartile had a higher risk of having metabolic syndrome than those in the lowest quartile (OR = 6.14 and 2.94 for men and women, respectively). After further adjustment for BMI, metabolic syndrome risk remained significantly increased with increasing leptin quartiles in men. Finally, increased leptin levels were a predictor of metabolic syndrome in men and women. Conclusions Serum leptin levels are correlated with CVD risk and metabolic syndrome. Analysis of leptin as part of routine physical examinations may prove beneficial for early diagnosis of metabolic syndrome. PMID:21526991

  7. Brief Report: Plasma Leptin Levels Are Elevated in Autism: Association with Early Onset Phenotype?

    ERIC Educational Resources Information Center

    Ashwood, Paul; Kwong, Christina; Hansen, Robin; Hertz-Picciotto, Irva; Croen, Lisa; Krakowiak, Paula; Walker, Wynn; Pessah, Isaac N.; Van de Water, Judy

    2008-01-01

    There is evidence of both immune dysregulation and autoimmune phenomena in children with autism spectrum disorders (ASD). We examined the hormone/cytokine leptin in 70 children diagnosed with autism (including 37 with regression) compared with 99 age-matched controls including 50 typically developing (TD) controls, 26 siblings without autism, and…

  8. Serum levels of mitochondrial uncoupling protein 1, leptin, and lipids during late pregnancy and the early postpartum period in mares.

    PubMed

    Arfuso, F; Giannetto, C; Rizzo, M; Fazio, F; Giudice, E; Piccione, G

    2016-09-15

    The aim of this study was to investigate the changes of serum mitochondrial uncoupling protein 1 (UCP1) and leptin levels as well as of lipid and lipoprotein profiles in mares during the peripartum period. Ten pregnant mares (group A) were monitored from 15 ± 3 days of pregnancy until 15 days after foaling, and 10 nonpregnant nonlactating mares constituted the control (group B). In group A, blood sampling was performed on Days 15 ± 3 and 7 ± 3 before foaling, on the day of foaling, and on Days 7 and 15 after foaling. In group B, blood sampling was performed on the same days as in group A. Serum levels were determined for UCP1, leptin, total lipids, phospholipids, triglycerides, total cholesterol (Total-Chol), high-density lipoproteins, low-density lipoproteins (LDLs), and very low-density lipoproteins (VLDLs). Two-way repeated-measures ANOVA was applied to evaluate the effects of peripartum period and group membership. All studied parameters except phospholipid levels (P > 0.05) showed significant changes in group A over the peripartum period (P < 0.0001). A significant effect of pregnancy was found on all studied parameters (P < 0.001), which showed lower levels in group A than in group B for most of the time points considered. Significant negative correlations were found between UCP1 and total lipids, triglycerides, VLDLs, Total-Chol, and LDL values. Positive correlations were found between leptin and total lipids, triglycerides, VLDLs, Total-Chol, and LDLs. These changes observed in mares during the peripartum period could represent a response to hormonal and metabolic adaptations occurring during specific physiological conditions such as late pregnancy and early postpartum. These changes should compensate for the energy loss occurring during these particular life phases and ensure a good body condition to protect mares against negative energy balance. PMID:27165993

  9. Leptin: a possible metabolic signal affecting reproduction.

    PubMed

    Spicer, L J

    2001-11-01

    Since its discovery in 1994, leptin, a protein hormone synthesized and secreted by adipose tissue, has been shown to regulate feed intake in several species including sheep and pigs. Although a nimiety of information exists regarding the physiological role of leptin in rodents and humans, the regulation and action of leptin in domestic animals is less certain. Emerging evidence in several species indicates that leptin may also affect the hypothalamo-pituitary-gonadal axis. Leptin receptor mRNA is present in the anterior pituitary and hypothalamus of several species, including sheep. In rats, effects of leptin on GnRH, LH and FSH secretion have been inconsistent, with leptin exhibiting both stimulatory and inhibitory action in vivo and in vitro. Evidence to support direct action of leptin at the level of the gonad indicates that the leptin receptor and its mRNA are present in ovarian tissue of several species, including cattle. These leptin receptors are functional, since leptin inhibits insulin-induced steroidogenesis of both granulosa and thecal cells of cattle in vitro. Leptin receptor mRNA is also found in the testes of rodents. As with the ovary, these receptors are functional, at least in rats, since leptin inhibits hCG-induced testosterone secretion by Leydig cells in vitro. During pregnancy, placental production of leptin may be a major contributor to the increase in maternal leptin in primates but not rodents. However, in both primates and rodents, leptin receptors exist in placental tissues and may regulate metabolism of the fetal-placental unit. As specific leptin immunoassays are developed for domestic animals, in vivo associations may then be made among leptin, body energy stores, dietary energy intake and reproductive function. This may lead to a more definitive role of leptin in domestic animal reproduction. PMID:11872320

  10. Astrocyte Leptin Receptor (ObR) and Leptin Transport in Adult-Onset Obese Mice

    PubMed Central

    Pan, Weihong; Hsuchou, Hung; He, Yi; Sakharkar, Amul; Cain, Courtney; Yu, Chuanhui; Kastin, Abba J.

    2008-01-01

    The agouti viable yellow (Avy) spontaneous mutation generates an unusual mouse phenotype of agouti-colored coat and adult-onset obesity with metabolic syndrome. Persistent production of agouti signaling protein in Avy mice antagonizes melanocortin receptors in the hypothalamus. To determine how this disruption of neuroendocrine circuits affects leptin transport across the blood-brain barrier (BBB), we measured leptin influx in Avy and B6 control mice after the development of obesity, hyperleptinemia, and increased adiposity. After iv bolus injection, 125I-leptin crossed the BBB significantly faster in young (2 month old) B6 mice than in young Avy mice or in older (8 month old) mice of either strain. This difference was not observed by in situ brain perfusion studies, indicating the cause being circulating factors, such as elevated leptin levels or soluble receptors. Thus, Avy mice showed peripheral leptin resistance. ObRa, the main transporting receptor for leptin at the BBB, showed no change in mRNA expression in the cerebral microvessels between the age-matched (2 month old) Avy and B6 mice. Higher ObRb mRNA was seen in the Avy microvasculature with unknown significance. Immunofluorescent staining unexpectedly revealed that many of the ObR(+) cells were astrocytes and that the Avy mice showed significantly more ObR(+) astrocytes in the hypothalamus than the B6 mice. Although leptin permeation from the circulation was slower in the Avy mice, the increased ObR expression in astrocytes and increased ObRb mRNA in microvessels suggest the possibility of heightened central nervous system sensitivity to circulating leptin. PMID:18292187

  11. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy

    PubMed Central

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m2. Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD. PMID:27307101

  12. Association of Increased Serum Leptin with Ameliorated Anemia and Malnutrition in Stage 5 Chronic Kidney Disease Patients after Parathyroidectomy.

    PubMed

    Jiang, Yao; Zhang, Jingjing; Yuan, Yanggang; Zha, Xiaoming; Xing, Changying; Shen, Chong; Shen, Zhixiang; Qin, Chao; Zeng, Ming; Yang, Guang; Mao, Huijuan; Zhang, Bo; Yu, Xiangbao; Sun, Bin; Ouyang, Chun; Xu, Xueqiang; Ge, Yifei; Wang, Jing; Zhang, Lina; Cheng, Chen; Yin, Caixia; Zhang, Jing; Chen, Huimin; Ma, Haoyang; Wang, Ningning

    2016-01-01

    Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD. PMID:27307101

  13. Levels of Analysis in Higher Education Research

    ERIC Educational Resources Information Center

    Tight, Malcolm

    2012-01-01

    This article examines the levels of analysis adopted in higher education research, using a database of 567 articles published in 15 leading higher education journals internationally during 2010. Level of analysis is a relatively overlooked issue in this field of research, when compared with methodology, theory and/or topic--to which it is, of…

  14. Growth hormone-binding protein directly depends on serum leptin levels in adults with different nutritional status.

    PubMed

    Llopis, M A; Granada, M L; Cuatrecasas, G; Formiguera, X; Sánchez-Planell, L; Sanmartí, A; Alastrué, A; Rull, M; Corominas, A; Foz, M

    1998-06-01

    The aim of this work was to assess the relationship between GH-binding protein (GHBP) and leptin. Both peptides are nutritionally regulated, but the recent implication of a role for leptin in the GH axis requires further study. To avoid the sexual dimorphism in leptin values, we performed leptin standardization according to gender (SD score-leptin). The relationship between SD score-leptin and GHBP was studied in 128 adults with different nutritional status [8 groups according to body mass index (BMI)], ranging from severely underweight anorexia nervosa to highly morbid obesity. Both GHBP and SD score-leptin significantly increased according to BMI within the range from 18-27 kg/m2, whereas no significant differences were found among underweight groups (BMI, < 18 kg/m2) or among obesity grades (BMI, > 27 kg/m2). We found a strong correlation between GHBP and SD score-leptin (r = 0.8; P < 0.0001). Multiple regression analysis revealed SD score-leptin to be a significant determinant of GHBP, accounting for 64% of the variation, whereas BMI did not contribute further to explaining changes in GHBP. This suggests a physiological pathway involving both GHBP (the soluble fraction of GH receptor) and leptin. Thus, we might speculate that leptin could be the signal that induces the related nutritional changes observed in GHBP/GH receptor expression. PMID:9626132

  15. Plasma kisspeptin levels are elevated in cord blood and present sexual dimorphism in the adult population: relation with leptin, gonadotropins and anthropometrical data.

    PubMed

    Pita, Jimena; Rado-Peralta, Sandra; Gavela-Pérez, Teresa; Aragón, Isabel; Barrios, Vicente; Rovira, Adela; Argente, Jesús; Soriano-Guillén, Leandro

    2011-05-01

    Kisspeptin, the product of the hypothalamic KISS1 gene, is a main regulator of the hypothalamic-pituitary-gonadal axis and could be a link between metabolism and reproduction through its interaction with leptin. Kisspeptin could be involved in gonadotropin regulation and responsive to leptin levels from the first stages of life, exhibiting, as does leptin, sexual dimorphism. To test our hypothesis, we have analyzed plasma kisspeptin levels and their possible relationship with gonadotropins and leptin in a cohort composed of newborns (n = 86) and adults (n = 55). Plasma kisspeptin, gonadotropin and leptin levels were measured by RIA and multiplexed bead immunoassays, respectively. We have built a multivariate linear regression model (analyzing kisspeptin and LH separately as dependent variables) by stepwise analysis, incorporating the variables that had shown significant correlation in the univariate analysis. Cord blood samples exhibited high kisspeptin levels 127.01(113-141.02 pmol/l), but these were not sexually dimorphic. The adult population exhibited sexual dimorphism (3.72(2.95-4.49) vs. 1.77(1.23-2.31)pmol/l women vs. men, p<0.05). Leptin levels showed sexual dimorphism in cord blood samples and also in the adult population. Furthermore, there was a significant interaction between LH and kisspeptin levels and kisspeptin was negatively correlated with age. The high kisspeptin levels observed in cord blood, with no sexual dimorphism, suggest a placental source. The sexual dimorphism exhibited in adulthood supports the notion that there are different sources and/or differential kisspeptin regulation between men and women. PMID:21295095

  16. Association between leptin and delirium in elderly inpatients

    PubMed Central

    Sánchez, Julio C; Ospina, Jenny P; González, Martha I

    2013-01-01

    Leptin is a hormone with significant effects on the brain, both at the cellular level and cognitive level. This study aimed to establish the association between leptin levels and delirium in a Colombian elderly population. 115 patients older than 60 years were included. Leptin was measured by enzyme-linked immunosorbent assay after overnight fasting and Mini-Mental State Examination and Confusion Assessment Method (CAM) tests were employed. Delirium was diagnosed using CAM in 23.48% of patients, being most frequent in men. There were no significant differences in hematology and renal test values between patients with delirium and those without delirium, but cerebrovascular diagnoses were more frequent in patients with delirium. No correlation with any specific medication was found, but patients with delirium had a higher number of comorbidities and medications. Leptin levels were significantly lower in patients with delirium and correlated negatively with the number of diagnoses and medications, but not with age, gender, body mass index, or hematology and renal test results. Leptin levels may have a role in the pathophysiological process of delirium and low leptin could be a useful clinical biomarker to establish risk in elderly patients given the association with delirium. PMID:23717044

  17. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control

    PubMed Central

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  18. Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control.

    PubMed

    Yan, Ai-Fen; Chen, Ting; Chen, Shuang; Ren, Chun-Hua; Hu, Chao-Qun; Cai, Yi-Ming; Liu, Fang; Tang, Dong-Sheng

    2016-01-01

    In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin-AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine-regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID:27249000

  19. Energy stores, lipid mobilization and leptin endocrinology of rainbow trout.

    PubMed

    Johansson, Marcus; Morgenroth, Daniel; Einarsdottir, Ingibjörg Eir; Gong, Ningping; Björnsson, Björn Thrandur

    2016-08-01

    The physiological role of leptin in fish is not fully elucidated. In the present study, the involvement of the leptin system in lipid deposition and mobilization in rainbow trout during feeding and 1, 2 and 4 weeks of fasting was investigated in two lines of rainbow trout with different muscle and visceral adiposity: a fat line (FL) with high total energy reserves, high muscle adiposity, but low visceral adiposity and a lean line (LL) with lower total energy reserves and lower muscle adiposity, but higher visceral adiposity. During 4 weeks of fasting, muscle lipids decreased by 63 % in the FL fish, while no such energy mobilization from muscle occurred in the LL fish. On the other hand, lipid stores in liver and visceral adipose tissue was utilized to a similar extent by the two fish lines during fasting. Under normal feeding conditions, plasma leptin levels were higher in the LL than the FL fish, suggesting a possible contribution of visceral adipocytes to plasma leptin levels. Plasma leptin-binding protein levels did not differ between the lines and were not affected by fasting. After 4 weeks of fasting, the long leptin receptor and the leptin-binding protein isoforms 1 and 3 muscle expression increased in the LL fish, as well as hepatic expression of leptin A1 and the two binding protein isoforms. These responses were not seen in the FL fish. The data suggest that the Lep system in rainbow trout is involved in regulation of energy stores and their mobilization. PMID:27083432

  20. Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features

    PubMed Central

    Sarandöl, Emre; Kırhan, Emine; Özkaya, Güven; Kırlı, SelcÇuk

    2012-01-01

    Objective: Brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and leptin have been hypothesized to be involved in the neurobiology of depression. The aim of this study was to investigate BDNF, VEGF and leptin levels in patients with severe melancholic depression. Methods: A total of 40 drug-free patients with major depressive disorder (MDD) with melancholic features and 40 healthy controls were included in the study. Demographic information, psychiatric evaluation and physical examination were documented for both groups. Serum BDNF, VEGF levels were determined by enzyme-linked immunosorbent assay and leptin with radioimmunoassay methods. The Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were applied to the patients. Results: There were no significant differences in serum BDNF, VEGF and leptin levels between the patient and control groups. There was a negative correlation between BDNF levels and the number of depressive episodes. It was noted that VEGF levels decreased with increasing severity of depression. Conclusions: These findings suggest that BDNF levels might be associated with the recurrence of depression and VEGF levels might be a determinant of the severity of depression. PMID:23983958

  1. Leptin enhances endothelial cell differentiation and angiogenesis in murine embryonic stem cells.

    PubMed

    Kurtovic, Silvia; Ng, Tina T; Gupta, Ankur; Arumugaswami, Vaithilingaraja; Chaiboonma, Kira L; Aminzadeh, Mohammad Amin; Makkar, Raj; Dafoe, Donald C; Talavera-Adame, Dodanim

    2015-01-01

    The metabolic regulation of leptin and its angiogenic effects have been well characterized in adult mammals. However, the role of leptin in the differentiation of embryonic stem cells (ESCs) to endothelial cells (ECs) has not been characterized. We hypothesized that leptin enhances the generation of ECs derived from ESCs and, in this way, promotes angiogenesis in embryonic vessels. To address this hypothesis, we utilized an in vitro model consisting of murine ESCs-derived embryoid bodies (EBs). Vascular density, EC and angiogenesis markers as well as phosphorylation levels of signal transducer and activator of transcription 3 (pSTAT3) were investigated in leptin-treated EBs and in untreated EBs as controls. ESC-derived ECs were isolated by magnetic sorting based on the expression of platelet endothelial cell adhesion molecule (PECAM-1/CD31). Significant upregulation of EC and angiogenic markers as well as higher vessel density were found in leptin-treated EBs compared to controls. CD31 positive enriched cells derived from leptin-treated EBs had improved proliferation and survival rate and showed higher levels of pSTAT3. These results suggested that leptin promotes EC differentiation and angiogenesis in mouse EBs and that janus tyrosine kinase (JAK)/STAT pathway can play a role in this biological process. Leptin-mediated EC differentiation and angiogenesis in ESCs can be a useful application towards regenerative medicine and tissue engineering. PMID:25250519

  2. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence.

    PubMed

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m(2) and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m(2). Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  3. Negative Correlation between Serum S100B and Leptin Levels in Schizophrenic Patients During Treatment with Clozapine and Risperidone: Preliminary Evidence

    PubMed Central

    Hendouei, Narjes; Hosseini, Seyed Hamzeh; Panahi, Amin; Khazaeipour, Zahra; Barari, Fatemeh; Sahebnasagh, Adeleh; Ala, Shahram

    2016-01-01

    Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source. In this study we evaluated the relationship between S100B and leptin in schizophrenic patients under treatment with clozapine and risperidone.This study included 19 patients meeting the DSM-IV-TR criteria for schizophrenia, having body mass index (BMI) of 16- 25 kg/m2 and suffering schizophrenia for more than 3 years and from this study. Twenty five healthy controls were group matched for age and gender whose BMI was 16-25 kg/m2. Serum S100B and leptin levels and positive and negative symptom scale (PANSS) were assessed at admission and after six weeks. During the study, S100B showed a strong and negative correlation with leptin (r = -0.5, P = 0.01). Also, there were negative correlation between serum S100B level and PANSS negative subscale after 6 weeks of treatment (r = -0.048, P = 0.8). Positive correlation between leptin level and PANSS suggested a potential role for leptin which can mediate the link between antipsychotic induced weight gain and therapeutic response in schizophrenia. PMID:27610173

  4. Exercise prevents leptin-induced increase in blood pressure in Sprague-Dawley rats.

    PubMed

    Farhana, K; Effendi, I; Caszo, Brinnell; Satar, Nuraliza Abdul; Singh, H J

    2014-06-01

    Although leptin has been shown to increase blood pressure (BP), it is however unclear if this increase can be prevented by exercise. This study therefore investigated the effect of leptin treatment with concurrent exercise on blood pressure (BP), sodium output, and endothelin-1 (ET-1) levels in normotensive rats. Male Sprague-Dawley rats weighing 250-270 g were divided into four groups consisting of a control group (n = 6), leptin-treated (n = 8), non-leptin-treated exercise group (n = 8), and a leptin-treated exercise group (n = 8). Leptin was given subcutaneously daily for 14 days (60 μg/kg/day). Animals were exercised on a treadmill for 30 min at a speed of 0.5 m/s and at 5° incline four times per week. Measurement of systolic blood pressure (SBP) and collection of urine samples for estimation of sodium and creatinine was done once a week. Serum samples were collected at the end of the experiment for determination of sodium, creatinine and ET-1. At day 14, mean SBP and serum ET-1 level in the leptin-treated group was significantly higher than that in the control group whereas mean SBP and serum ET-1 level was significantly lower in the leptin-treated exercise group than those in leptin-treated and control groups. Creatinine clearance, urinary sodium excretion, and urine output were not different between the four groups. Regular treadmill exercise prevents leptin-induced increases in SBP in rats, which might in part result from increased urinary sodium excretion and preventing the leptin-induced increases in serum ET-1 concentration. PMID:24711061

  5. Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

    SciTech Connect

    Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar; Tokar, Erik J.; Kadiiska, Maria B.; Waalkes, Michael P.; Mason, Ronald P.; Chatterjee, Saurabh

    2013-06-15

    Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation, protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates protein

  6. Leptin changes differentiation fate and induces senescence in chondrogenic progenitor cells

    PubMed Central

    Zhao, X; Dong, Y; Zhang, J; Li, D; Hu, G; Yao, J; Li, Y; Huang, P; Zhang, M; Zhang, J; Huang, Z; Zhang, Y; Miao, Y; Xu, Q; Li, H

    2016-01-01

    Body weight is a component of the mechanical theory of OA (osteoarthritis) pathogenesis. Obesity was also found to be a risk factor for digital OA involving non-weight-bearing joints, which suggested that metabolism influences the occurrence and progression of OA. The metabolic origin of OA has been partially attributed to the involvement of adipokines, such as leptin, the levels of which are significantly and positively correlated with cartilage degeneration in OA patients. However, the mechanisms by which leptin-induced cartilage degeneration occurs are poorly understood. The discovery of chondrogenic progenitor cells (CPCs) opened up new opportunities for investigation. Investigating the effects of leptin on differentiation and proliferation in CPCs would increase our understanding of the roles played by leptin in the aetiology and development of OA. Here, CPCs were harvested using single-cell sorting from rat cartilage tissues to obtain mesenchymal stem-like cells, which possess clonogenicity, proliferation and stemness. High doses of leptin decreased the ability of the CPCs to migrate, inhibited their chondrogenic potential and increased their osteogenic potential, suggesting that leptin changes differentiation fates in CPCs. High doses of leptin induced cell cycle arrest and senescence in CPCs by activating the p53/p21 pathway and inhibiting the Sirt1 pathway. Inhibiting the Sirt1 pathway accelerated cartilage senescence in knockout (KO) mice. Activating the leptin pathway induced higher Ob-Rb expression and was significantly correlated with cartilage degeneration (lower levels of Coll-2) and tissue senescence (higher levels of p53/p21 and lower levels of Sirt1) in OA patients, suggesting that leptin-induced CPCs senescence contributes to the development of OA. Taken together, our results reveal new links between obesity and cartilage damage that are induced by leptin-mediated effects on cell behaviour and senescence. PMID:27077804

  7. Leptin: pharmacological aspects in gynecology.

    PubMed

    Sorace, M; Tripodi, L; Tripodi, A; Groppetti, D; Cremonesi, F

    2006-01-01

    Hematic levels of leptin vary in relation to numerous metabolic factors and are able to interact in perfect synchrony with the hormones involved in the hypothalamus-pituitary-ovarian axis during the various phases of the reproductive cycle. In general it is maintained that the complex and multiple action mechanisms of leptin need to be clarified by further in-depth research studies. It is likely that valid pharmacological applications of leptin will be found for human use although it is too premature to talk about concrete pharmacological answers and to formulate the relative complete technical protocols. In medicine the therapeutic use of leptin for humans has been reported in only a few cases. In fact human recombinant leptin has already been administered in gynecology for hypothalamic amenorrhea with precise protocols. In addition, very recent studies have provided the basis for new strategies to be developed concerning the use of leptin to fight multiple sclerosis. At present there are considerable technical and economic problems in the production of leptin on a large scale. Most likely these problems will be overcome in the foreseeable future, and will involve new techniques related to genetics, cellular reprograming, and stem cells. In fact, new pharmacogenetic research has provided encouraging results for the production in industrial quantities of a more effective and fail-proof leptin. Even considering that norms have not yet been proposed for pharmacological interventions with leptin for use directly on humans, in our work we have studied by immunohistochemistry methods the distribution of leptin and its receptor (Ob-R) in the ovaries of the female dog as a biological model, in the pre- and postpubertal phases and in other phases of the ovarian cycle. Given the hypothesis that the information obtained from immunohistochemical localization of the hormone and its receptor in various ovarian structures is transferable to humans, it could be useful to define

  8. Peripheral Leptin Regulates Bone Formation

    PubMed Central

    Turner, Russell T.; Kalra, Satya P.; Wong, Carmen P.; Philbrick, Kenneth A.; Lindenmaier, Laurence B.; Boghossian, Stephane; Iwaniec, Urszula T.

    2012-01-01

    Substantial evidence does not support the prevailing view that leptin, acting through a hypothalamic relay, decreases bone accrual by inhibiting bone formation. To clarify the mechanisms underlying regulation of bone architecture by leptin, we evaluated bone growth and turnover in wild type (WT) mice, leptin receptor-deficient db/db mice, leptin-deficient ob/ob mice and ob/ob mice treated with leptin. We also performed hypothalamic leptin gene therapy to determine the effect of elevated hypothalamic leptin levels on osteoblasts. Finally, to determine the effects of loss of peripheral leptin signaling on bone formation and energy metabolism, we used bone marrow (BM) from WT or db/db donor mice to reconstitute the hematopoietic and mesenchymal stem cell compartments in lethally irradiated WT recipient mice. Decreases in bone growth, osteoblast-lined bone perimeter and bone formation rate were observed in ob/ob mice and greatly increased in ob/ob mice following subcutaneous administration of leptin. Similarly, hypothalamic leptin gene therapy increased osteoblast-lined bone perimeter in ob/ob mice. In spite of normal osteoclast-lined bone perimeter, db/db mice exhibited a mild but generalized osteopetrotic-like (calcified cartilage encased by bone) skeletal phenotype and greatly reduced serum markers of bone turnover. Tracking studies and histology revealed quantitative replacement of BM cells following BM transplantation. WT mice engrafted with db/db BM did not differ in energy homeostasis from untreated WT mice or WT mice engrafted with WT BM. Bone formation in WT mice engrafted with WT BM did not differ from WT mice, whereas bone formation in WT mice engrafted with db/db cells did not differ from the low rates observed in untreated db/db mice. In summary, our results indicate that leptin, acting primarily through peripheral pathways, increases osteoblast number and activity. PMID:22887758

  9. Obesity-related hypertension: is there a role for selective leptin resistance?

    PubMed

    Correia, Marcelo L G; Haynes, William G

    2004-06-01

    Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited. PMID:15128477

  10. Leptin in teleostean fish, towards the origins of leptin physiology.

    PubMed

    Gorissen, Marnix; Flik, Gert

    2014-11-01

    Teleostean leptin was first cloned in 2005, more than a decade after the discovery of mammalian leptin. The reason for this delay lies in the very poor primary sequence conservation (∼13-25%) between mammalian and fish leptins. These low sequence conservations indicate a high degree of molecular evolvability and warrant a search for different and original functions of leptin in teleosts. Indeed, new and original insights are obtained because of the unique phylogenetic position of teleostean fish as the earliest vertebrates and because of their ectothermy, which means that teleosts are more flexible in changing their metabolism than mammals and leptin could play a role in this flexibility. Research during the last decade reveals that leptin is a truly pleiotropic hormone in fish and mammals alike, with functions among others in the regulation of food intake and body weight, development, but also in the regulation of the stress axis and acclimation processes to for instance low oxygen levels in the water. In this review, we provide an overview of the teleostean leptin work done in the last ten years, and demonstrate that the power of a comparative approach leads to new insights on the origins of leptin physiology. PMID:24977940

  11. Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis

    PubMed Central

    2010-01-01

    Introduction Increasing evidence support the regulatory role of leptin in osteoarthritis (OA). As high circulating concentrations of leptin disrupt the physiological function of the adipokine in obese individuals, the current study has been undertaken to determine whether the elevated levels of leptin found in the joint from obese OA patients also induce changes in the chondrocyte response to leptin. Methods Chondrocytes isolated from OA patients with various body mass index (BMI) were treated with 20, 100 or 500 ng/ml of leptin. The expression of cartilage-specific components (aggrecan, type 2 collagen), as well as regulatory (IGF-1, TGFβ, MMP-13, TIMP 2) or inflammatory (COX-2, iNOS, IL-1) factors was investigated by real-time PCR to evaluate chondrocyte responsiveness to leptin. Furthermore, the effect of body mass index (BMI) on leptin signalling pathways was analyzed with an enzyme-linked immunosorbent assay for STATs activation. Results Leptin at 20 ng/ml was unable to modulate gene expression in chondrocytes, except for MMP-13 in obese OA patients. Higher leptin levels induced the expression of IGF-1, type 2 collagen, TIMP-2 and MMP-13. However, the activity of the adipokine was shown to be critically dependent on both the concentration and the BMI of the patients with a negative association between the activation of regulated genes and BMI for 100 ng/ml of adipokine, but a positive association between chondrocyte responsiveness and BMI for the highest leptin dose. In addition, the gene encoding MMP-13 was identified as a target of leptin for chondrocytes originated from obese patients while mRNA level of TIMP-2 was increased in leptin-treated chondrocytes collected from normal or overweight patients. The adipokine at 500 ng/ml triggered signal transduction through a STAT-dependent pathway while 100 ng/ml of leptin failed to activate STAT 3 but induced STAT 1α phosphorylation in chondrocytes obtained from obese patients. Conclusions The current study

  12. Leptin receptor null mice with reexpression of LepR in GnRHR expressing cells display elevated FSH levels but remain in a prepubertal state.

    PubMed

    Allen, Susan J; Garcia-Galiano, David; Borges, Beatriz C; Burger, Laura L; Boehm, Ulrich; Elias, Carol F

    2016-06-01

    Leptin signals energy sufficiency to the reproductive hypothalamic-pituitary-gonadal (HPG) axis. Studies using genetic models have demonstrated that hypothalamic neurons are major players mediating these effects. Leptin receptor (LepR) is also expressed in the pituitary gland and in the gonads, but the physiological effects of leptin in these sites are still unclear. Female mice with selective deletion of LepR in a subset of gonadotropes show normal pubertal development but impaired fertility. Conditional deletion approaches, however, often result in redundancy or developmental adaptations, which may compromise the assessment of leptin's action in gonadotropes for pubertal maturation. To circumvent these issues, we adopted a complementary genetic approach and assessed if selective reexpression of LepR only in gonadotropes is sufficient to enable puberty and improve fertility of LepR null female mice. We initially assessed the colocalization of gonadotropin-releasing hormone receptor (GnRHR) and LepR in the HPG axis using GnRHR-IRES-Cre (GRIC) and LepR-Cre reporter (tdTomato or enhanced green fluorescent protein) mice. We found that GRIC and leptin-induced phosphorylation of STAT3 are expressed in distinct hypothalamic neurons. Whereas LepR-Cre was observed in theca cells, GRIC expression was rarely found in the ovarian parenchyma. In contrast, a subpopulation of gonadotropes expressed the LepR-Cre reporter gene (tdTomato). We then crossed the GRIC mice with the LepR null reactivable (LepR(loxTB)) mice. These mice showed an increase in FSH levels, but they remained in a prepubertal state. Together with previous findings, our data indicate that leptin-selective action in gonadotropes serves a role in adult reproductive physiology but is not sufficient to allow pubertal maturation in mice. PMID:27101301

  13. Web life: Confused at a Higher Level

    NASA Astrophysics Data System (ADS)

    2010-08-01

    This two-person blog owes its name to Enrico Fermi, who supposedly informed a visiting lecturer that although he used to be confused about the lecture topic, "having listened to your lecture, I am still confused. But on a higher level".

  14. Leptin concentration in plasma and in milk during the interpartum period in the mare.

    PubMed

    Romagnoli, U; Macchi, E; Romano, G; Motta, M; Accornero, P; Baratta, M

    2007-01-01

    The aim of this work is to investigate on plasma profiles of leptin and estradiol 17beta during the interpartum period and leptin concentrations in the milk and in the colostrum during the period from parturition to the successive delivery in mare. Leptin plasma concentration varied from 5.1+/-2.3 ng/ml after the first parturition (week 0) to 3.0+/-0.7 at week 21 (p<0.05), then it increased to maximal level at week 49 (6.9+/-1.0 ng/ml, p<0.05). Leptin concentration in the colostrum and in the milk has been significantly (p<0.05) higher than that in plasma samples at week 1 (milk 8.8+/-2.3 versus plasma 5.2+/-0.6 ng/ml) and between week 12 and 17. This difference may be explained with a local leptin production at mammary level and supports a role of leptin in the mammary gland and/or in foal intestine. Estradiol 17beta increased from week 15 (17.9+/-2.3 pg/ml) up to 487.9+/-67.7 pg/ml at week 43. Plasma estradiol 17beta rise anticipated by 4 weeks plasma leptin increase and it does not seem to be positively correlated to leptin secretion. PMID:16524675

  15. The influence of leptin on Th1/Th2 balance in obese children with asthma*

    PubMed Central

    Youssef, Doaa Mohammed; Elbehidy, Rabab Mohamed; Shokry, Dina Mahamoud; Elbehidy, Eman Mohamed

    2013-01-01

    OBJECTIVE: In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS: We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS: Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS: Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity. PMID:24310629

  16. Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women.

    PubMed

    Kato, Sumie; Abarzua-Catalan, Lorena; Trigo, César; Delpiano, Ana; Sanhueza, Cristobal; García, Karen; Ibañez, Carolina; Hormazábal, Katherine; Diaz, Daniela; Brañes, Jorge; Castellón, Enrique; Bravo, Erasmo; Owen, Gareth; Cuello, Mauricio A

    2015-08-28

    The evidence linking obesity with ovarian cancer remains controversial. Leptin is expressed at higher levels in obese women and stimulates cell migration in other epithelial cancers. Here, we explored the clinical impact of overweight/obesity on patient prognosis and leptin's effects on the metastatic potential of ovarian cancer cells. We assessed clinical outcomes in 70 ovarian cancer patients (33 healthy weight and 37 overweight) that were validated with an external cohort from The Cancer Genome Atlas (TCGA) database. Progression-free and overall survival rates were significantly decreased in overweight patients. Similarly, a worse overall survival rate was found in TCGA patients expressing higher leptin/OB-Rb levels. We explored serum and ascites leptin levels and OB-Rb expression in our cohort. Serum and ascites leptin levels were higher in overweight patients experiencing worse survival. OB-Rb was more highly expressed in ascites and metastases than in primary tumors. Leptin exposure increased cancer cell migration/invasion through leptin-mediated activation of JAK/STAT3, PI3/AKT and RhoA/ROCK and promoted new lamellipodial, stress-fiber and focal adhesion formation. Leptin also contributed to the maintenance of stemness and the mesenchymal phenotype in ovarian cancer cells. Our findings demonstrate that leptin stimulated ovarian cancer cell migration and invasion, offering a potential explanation for the poor prognosis among obese women. PMID:26053184

  17. Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women

    PubMed Central

    Kato, Sumie; Abarzua-Catalan, Lorena; Trigo, César; Delpiano, Ana; Sanhueza, Cristobal; García, Karen; Ibañez, Carolina; Hormazábal, Katherine; Diaz, Daniela; Brañes, Jorge; Castellón, Enrique; Bravo, Erasmo; Owen, Gareth; Cuello, Mauricio

    2015-01-01

    The evidence linking obesity with ovarian cancer remains controversial. Leptin is expressed at higher levels in obese women and stimulates cell migration in other epithelial cancers. Here, we explored the clinical impact of overweight/obesity on patient prognosis and leptin's effects on the metastatic potential of ovarian cancer cells. We assessed clinical outcomes in 70 ovarian cancer patients (33 healthy weight and 37 overweight) that were validated with an external cohort from The Cancer Genome Atlas (TCGA) database. Progression-free and overall survival rates were significantly decreased in overweight patients. Similarly, a worse overall survival rate was found in TCGA patients expressing higher leptin/OB-Rb levels. We explored serum and ascites leptin levels and OB-Rb expression in our cohort. Serum and ascites leptin levels were higher in overweight patients experiencing worse survival. OB-Rb was more highly expressed in ascites and metastases than in primary tumors. Leptin exposure increased cancer cell migration/invasion through leptin-mediated activation of JAK/STAT3, PI3/AKT and RhoA/ROCK and promoted new lamellipodial, stress-fiber and focal adhesion formation. Leptin also contributed to the maintenance of stemness and the mesenchymal phenotype in ovarian cancer cells. Our findings demonstrate that leptin stimulated ovarian cancer cell migration and invasion, offering a potential explanation for the poor prognosis among obese women. PMID:26053184

  18. Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells

    PubMed Central

    Shen, Minqian; Shi, Haifei

    2016-01-01

    Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action of leptin is uncertain. To investigate potential inhibitory effects of estrogens on leptin-induced HCC development, HCC cell line HepG2 cells were treated with leptin in combination with 17 β-estradiol (E2), estrogen receptor-α (ER-α) selective agonist PPT, ER-β selective agonist DPN, or G protein-coupled ER (GPER) selective agonist G-1. Cell number, proliferation, and apoptosis were determined, and leptin- and estrogen-related intracellular signaling pathways were analyzed. HepG2 cells expressed a low level of ER-β mRNA, and leptin treatment increased ER-β expression. E2 suppressed leptin-induced HepG2 cell proliferation and promoted cell apoptosis in a dose-dependent manner. Additionally E2 reversed leptin-induced STAT3 and leptin-suppressed SOCS3, which was mainly achieved by activation of ER-β. E2 also enhanced ERK via activating ER-α and GPER and activated p38/MAPK via activating ER-β. To conclude, E2 and its receptors antagonize the oncogenic actions of leptin in HepG2 cells by inhibiting cell proliferation and stimulating cell apoptosis, which was associated with reversing leptin-induced changes in SOCS3/STAT3 and increasing p38/MAPK by activating ER-β, and increasing ERK by activating ER-α and GPER. Identifying roles of different estrogen receptors would provide comprehensive understanding of estrogenic mechanisms in HCC development and shed light on potential treatment for HCC patients. PMID:26982332

  19. Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells.

    PubMed

    Shen, Minqian; Shi, Haifei

    2016-01-01

    Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action of leptin is uncertain. To investigate potential inhibitory effects of estrogens on leptin-induced HCC development, HCC cell line HepG2 cells were treated with leptin in combination with 17 β-estradiol (E2), estrogen receptor-α (ER-α) selective agonist PPT, ER-β selective agonist DPN, or G protein-coupled ER (GPER) selective agonist G-1. Cell number, proliferation, and apoptosis were determined, and leptin- and estrogen-related intracellular signaling pathways were analyzed. HepG2 cells expressed a low level of ER-β mRNA, and leptin treatment increased ER-β expression. E2 suppressed leptin-induced HepG2 cell proliferation and promoted cell apoptosis in a dose-dependent manner. Additionally E2 reversed leptin-induced STAT3 and leptin-suppressed SOCS3, which was mainly achieved by activation of ER-β. E2 also enhanced ERK via activating ER-α and GPER and activated p38/MAPK via activating ER-β. To conclude, E2 and its receptors antagonize the oncogenic actions of leptin in HepG2 cells by inhibiting cell proliferation and stimulating cell apoptosis, which was associated with reversing leptin-induced changes in SOCS3/STAT3 and increasing p38/MAPK by activating ER-β, and increasing ERK by activating ER-α and GPER. Identifying roles of different estrogen receptors would provide comprehensive understanding of estrogenic mechanisms in HCC development and shed light on potential treatment for HCC patients. PMID:26982332

  20. A Comparative Study of Serum and Follicular Fluid Leptin Concentrations among Explained Infertile, Unexplained Infertile and Fertile Women

    PubMed Central

    Kamyabi, Zahra; Gholamalizade, Tayebe

    2015-01-01

    Background The relationship between metabolism and reproduction has been always considered as an important topic in female endocrinology. It seems that leptin is one of the involved factors in infertility. Leptin, in addition to regulating body weight plays an important role in regulation of endocrine, reproductive and immune systems. The aim of this stduy is to compare serum and follicular fluid leptin concentrations in order to find the role of leptin level in infertility. Materials and Methods This case-control study was performed from September 2010 to March 2013. A total of 90 women referred to the Infertility Center of Afzalipour Hos- pital, Kerman, Iran, and divided into three equal groups (n=30/per group) of explained infertile (including 4 subgroups), unexplained infertile and normal fertile (control group). The three groups were matched in regard to demographic features [age: 20-40 years and body mass index (BMI): 20-25]. In order to determine leptin level, blood sample and fol- licular fluid were taken one hour prior and at the time of follicular puncture, respectively. Serum and follicular fluid leptin levels were measured using enzyme-linked immune sorbent assay (ELISA). Data were analyzed using descriptive-analytic tests, like Mann- Whitney and Kruskal Wallis tests, through Statistical Package for the Social Sciences (SPSS) version 16. Results In explained infertile and fertile groups, as opposed to unexplained infertile group, mean leptin level was lower in follicular fluid than in serum. Mean follicular fluid leptin concentration in women with unexplained infertility was higher com- pared to the other two groups. Women with unexplained infertility had lower level of serum leptin in comparison to the other two groups. Follicular fluid leptin level in all subgroups of explained infertile group was lower as compared to unexplained and fertile women. Conclusion The results suggested that high leptin level of follicular fluid is one of the main factors

  1. Psychiatric symptoms and leptin in obese patients who were bariatric surgery candidates

    PubMed Central

    Changchien, Te-Chang; Tai, Chi-Ming; Huang, Chih-Kun; Chien, Chia-Chang; Yen, Yung-Chieh

    2015-01-01

    Objective There is a significant relationship between obesity and common mental symptoms (depression and anxiety symptoms). But the association between depression (or anxiety symptoms) and serum leptin is still unclear and controversial, despite the growing body of evidence supporting the existence of “leptin resistance” in obese persons. So we investigated whether common mental symptoms, obesity, and the interactive effect of these two factors have a relationship with leptin in obese patients who were candidates for bariatric surgery. Methods In all, 139 participants (mean age: 31.4 years, standard deviation: 9.3 years, 73.4% female) were enrolled at an obesity treatment center in southern Taiwan. Serum leptin levels and body mass index (BMI) were measured. The Chinese Health Questionnaire and Taiwanese Depression Questionnaire were administered. Results The mean BMI of our participants was 39.4 kg/m2 (±6.8), and the mean leptin level was 24.5 ng/mL (±9.4). In the multivariate regression models, Chinese Health Questionnaire-by-BMI and Taiwanese Depression Questionnaire-by-BMI interaction terms remained significant predictors of leptin level (β=0.16, P<0.0001; β=0.04, P<0.0001, respectively), after adjustment for age, sex, and history of hypertension, diabetes, and hyperlipidemia, despite the inverse correlation between Chinese Health Questionnaire (or Taiwanese Depression Questionnaire) and leptin. In addition, female patients had significantly higher leptin levels than male patients. Conclusion The present findings confirmed that the relationship between common mental symptoms and leptin is modulated by obesity in severely obese patients. Future studies should focus on further measures of leptin receptors or signaling on the basis of these interactive effects in psychiatry. PMID:26316761

  2. Targeted leptin receptor blockade: Role of VTA and NTS leptin receptors in body weight homeostasis

    PubMed Central

    Matheny, M.; Strehler, K.Y.E.; King, M.; Tümer, N.; Scarpace, P. J.

    2014-01-01

    The present investigation examined whether leptin stimulation of ventral tegmental area (VTA) or nucleus of the solitary tract (NTS) has a role in body weight homeostasis independent of the medial basal hypothalamus (MBH). To this end, recombinant adeno-associated viral techniques were employed to target leptin overexpression or overexpression of a dominant negative leptin mutant (Leptin Antagonist). Leptin Antagonist overexpression in MBH or VTA increased food intake and body weight to similar extents over 14 days in rats. Simultaneous overexpression of leptin in VTA with antagonist in MBH resulted in food intake and body weight gain that were less than with control treatment but greater than with leptin alone in VTA. Notably, leptin overexpression in VTA increased P-STAT3 in MBH along with VTA, and Leptin Antagonist overexpression in the VTA partially attenuated P-STAT3 levels in MBH. Interestingly, leptin antagonist overexpression elevated body weight gain, but leptin overexpression in the NTS failed to modulate either food intake or body weight despite increased P-STAT3. These data suggest that leptin function in the VTA participates in the chronic regulation of food consumption and body weight in response to stimulation or blockade of VTA leptin receptors. Moreover, one component of VTA-leptin action appears to be independent of the MBH, and another component appears to be related to leptin receptor-mediated P-STAT3 activation in the MBH. Finally, leptin receptors in the NTS are necessary for normal energy homeostasis, but appear to have mostly a permissive role. Direct leptin activation of NTS slightly increases UCP1, but has little effect on food consumption or body weight. PMID:24920667

  3. Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension.

    PubMed

    Bełtowski, Jerzy; Jamroz-Wiśniewska, Anna; Borkowska, Ewelina; Wójcicka, Grazyna

    2004-01-01

    Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin has not been elucidated. We investigated the effect of experimental hyperleptinemia on renal function, renal Na(+), K(+)-ATPase and ouabain-sensitive H(+), K(+)-ATPase activities in the rat. Leptin administered for 7 days (0.25 mg/kg twice daily sc) decreased food intake on 6th and 7th day of treatment but had no effect on body weight. Systolic blood pressure was 30.5% higher in leptin-treated animals. Urinary excretion of sodium decreased by 35.0% following leptin treatment. Leptin had no effect on potassium and phosphate excretion as well as on creatinine clearance. The activity of Na(+), K(+)-ATPase in the renal cortex and medulla was higher in leptin-treated rats by 32.4% and 84.2%, respectively. In contrast, leptin had no effect on either cortical or medullary ouabain-sensitive H(+), K(+)-ATPase. In pair-fed group, in which food intake was reduced to the level observed in leptin-treated group, no changes in sodium metabolism and renal Na(+), K(+)-ATPase were observed. Leptin decreased urinary excretion of nitric oxide metabolites by 55.0% and urinary excretion of cGMP by 26.3%. Plasma concentration of atrial natriuretic peptide tended to be higher and urinary excretion of urodilatin was 64.9% higher in leptin-treated animals. These data suggest that hyperleptinemia decreases natriuresis by up-regulating Na(+), K(+)-ATPase and stimulating tubular sodium reabsorption. This effect is mediated, at least in part, by deficiency of nitric oxide (NO). Abnormal renal sodium retention and vasoconstriction associated with NO deficiency may contribute to leptin-induced hypertension and to blood pressure elevation in hypertensive obese individuals. PMID:15156072

  4. Immunoreactivities of PPARγ2, leptin and leptin receptor in oviduct of Chinese brown frog during breeding period and pre-hibernation.

    PubMed

    Liu, Y; Weng, J; Huang, S; Shen, Y; Sheng, X; Han, Y; Xu, M; Weng, Q

    2014-01-01

    The Chinese brown frog (Rana dybowskii) is a special amphibian with one unique physiological phenomenon, which is that its oviduct expands prior to hibernation, instead of during the breeding period. In this study, we investigate the localization and expression level of PPARγ2, leptin and leptin receptor proteins in oviduct of Rana dybowskii during  breeding period and pre-hibernation. There were significant variations in oviductal weight and size, with values much lower in the breeding period than in pre-hibernation. PPARγ2 was observed in stromal and epithelial cells in both periods. Leptin was immunolocalized in epithelial cells in both periods, whereas leptin receptor was detected only in stromal cells. Consistently, the protein levels of PPARγ2, leptin and leptin receptor were higher in pre-hibernation as compared to the breeding period. These results suggested that oviduct was the target organ of leptin, which may play an important paracrine role in regulating the oviductal hypertrophy during pre-hibernation. PMID:25308849

  5. Structure, production and signaling of leptin

    PubMed Central

    Münzberg, Heike; Morrison, Christopher D.

    2014-01-01

    The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause morbid obesity, and it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. From the first discovery of the leptin deficient obese mouse (ob/ob), to the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, much has been learned about leptin and its action in the central nervous system. The initial high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint for distinct neuronal circuits that control energy homeostasis. A better understanding of the regulation and interconnection of these circuits will further guide and improve the development of safe and effective interventions to treat obesity. This review will highlight our current knowledge about the hormone leptin, its signaling pathways and its central actions to mediate distinct physiological functions. PMID:25305050

  6. Blockade of the cerebral aqueduct in rats provides evidence of antagonistic leptin responses in the forebrain and hindbrain.

    PubMed

    Vaill, Michael I; Desai, Bhavna N; Harris, Ruth B S

    2014-02-15

    Previously, we reported that low-dose leptin infusions into the fourth ventricle produced a small but significant increase in body fat. These data contrast with reports that injections of higher doses of leptin into the fourth ventricle inhibit food intake and weight gain. In this study, we tested whether exogenous leptin in the fourth ventricle opposed or contributed to weight loss caused by third ventricle leptin infusion by blocking diffusion of CSF from the third to the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions of PBS or 0.3 μg leptin/24 h from miniosmotic pumps. After 4 days, rats received a 3-μl cerebral aqueduct injection of saline or of thermogelling nanoparticles (hydrogel) that solidified at body temperature. Third ventricle leptin infusion inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated the effect of leptin on food intake and weight loss but had no effect on the weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but did not change energy expenditure. Blocking the aqueduct decreased expenditure of rats infused with PBS or leptin. Infusion of leptin into the third ventricle increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3 but decreased p-STAT3 in the medial NTS. These results support previous observations that low-level activation of hindbrain leptin receptors has the potential to blunt the catabolic effects of leptin in the third ventricle. PMID:24347057

  7. Blockade of the cerebral aqueduct in rats provides evidence of antagonistic leptin responses in the forebrain and hindbrain

    PubMed Central

    Vaill, Michael I.; Desai, Bhavna N.

    2013-01-01

    Previously, we reported that low-dose leptin infusions into the fourth ventricle produced a small but significant increase in body fat. These data contrast with reports that injections of higher doses of leptin into the fourth ventricle inhibit food intake and weight gain. In this study, we tested whether exogenous leptin in the fourth ventricle opposed or contributed to weight loss caused by third ventricle leptin infusion by blocking diffusion of CSF from the third to the fourth ventricle. Male Sprague-Dawley rats received third ventricle infusions of PBS or 0.3 μg leptin/24 h from miniosmotic pumps. After 4 days, rats received a 3-μl cerebral aqueduct injection of saline or of thermogelling nanoparticles (hydrogel) that solidified at body temperature. Third ventricle leptin infusion inhibited food intake and caused weight loss. Blocking the aqueduct exaggerated the effect of leptin on food intake and weight loss but had no effect on the weight of PBS-infused rats. Leptin reduced both body fat and lean body mass but did not change energy expenditure. Blocking the aqueduct decreased expenditure of rats infused with PBS or leptin. Infusion of leptin into the third ventricle increased phosphorylated STAT3 in the VMHDM of the hypothalamus and the medial NTS in the hindbrain. Blocking the aqueduct did not change hypothalamic p-STAT3 but decreased p-STAT3 in the medial NTS. These results support previous observations that low-level activation of hindbrain leptin receptors has the potential to blunt the catabolic effects of leptin in the third ventricle. PMID:24347057

  8. Short-Term Energy Deprivation Alters Activin A and Follistatin But Not Inhibin B Levels of Lean Healthy Women in a Leptin-Independent Manner

    PubMed Central

    Moragianni, Vasiliki A.; Aronis, Konstantinos N.; Chamberland, John P.

    2011-01-01

    Context: Leptin is a potent modulator of the hypothalamic-pituitary-gonadal axis mediating the effect of energy deprivation on several hypothalamic-pituitary-peripheral axes. Activin A, inhibin B, and follistatin (FST) also regulate the hypothalamic-pituitary-gonadal axis in humans. It remains unknown whether energy deprivation affects these hormone levels in a leptin-dependent or -independent manner. Objective: We investigated 1) day-night variability patterns of activin, inhibin, and FST in the fed state, 2) whether their levels are affected by fasting, and 3) whether such an effect is mediated by leptin in physiological replacement or pharmacological doses. Design: We conducted two studies in healthy, eumenorrheic females, each comprising three separate admissions. In study 1, six women were maintained for 72 h 1) on isocaloric diet, 2) fasting while receiving placebo, or 3) fasting while receiving metreleptin in physiological replacement doses. In study 2, five women were administered physiological or pharmacological metreleptin doses (0.01, 0.1, or 0.3 mg/kg iv four times daily). Results: Neither activin A nor FST had a pulsatile or day-night variability pattern. Inhibin B levels were also nonpulsatile, but a trend toward a day-night pattern was noted. When compared with the fed state, inhibin B levels remained unchanged, whereas FST levels increased (P = 0.01) and activin A decreased (P = 0.01) in the fasting state. These changes were not corrected with metreleptin administered in replacement or pharmacological doses. Conclusions: Short-term energy deprivation alters levels of activin A and FST, but these effects are not mediated by leptin. PMID:21917874

  9. Leptin in Alzheimer's disease.

    PubMed

    Magalhães, C A; Carvalho, M G; Sousa, L P; Caramelli, P; Gomes, K B

    2015-10-23

    Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly population. AD is histologically characterized by accumulation of amyloid-β protein (Aβ) on extracellular plaques and deposition of hyperphosphorylated tau protein in intracellular neurofibrillary tangles. Several studies have shown that obesity may precede dementia and that lifestyle factors play a critical role in the onset of AD. Furthermore, accumulating evidence indicates that obesity is an independent risk factor for developing AD. In this scenario, the understanding of the role of adipose tissue in brain health is essential to clarify the establishment of demential processes. The objective of this work was to review studies regarding leptin, an anorexigenic peptide hormone synthesized in adipocytes, in the context of dementia. Some authors proposed that leptin evaluation might be a better predictor of dementia than traditional anthropometric measures. Leptin, once established as a biomarker, could enhance the understanding of late-onset AD risk over the life course, as well as the clinical progression of prodromal state to manifested AD. Other studies have proposed that leptin presents neuroprotective activities, which could be explained by inhibiting the amyloidogenic process, reducing the levels of tau protein phosphorylation and improving the cognitive function. PMID:26279362

  10. Higher-level simulations of turbulent flows

    NASA Technical Reports Server (NTRS)

    Ferziger, J. H.

    1981-01-01

    The fundamentals of large eddy simulation are considered and the approaches to it are compared. Subgrid scale models and the development of models for the Reynolds-averaged equations are discussed as well as the use of full simulation in testing these models. Numerical methods used in simulating large eddies, the simulation of homogeneous flows, and results from full and large scale eddy simulations of such flows are examined. Free shear flows are considered with emphasis on the mixing layer and wake simulation. Wall-bounded flow (channel flow) and recent work on the boundary layer are also discussed. Applications of large eddy simulation and full simulation in meteorological and environmental contexts are included along with a look at the direction in which work is proceeding and what can be expected from higher-level simulation in the future.

  11. Differences in zinc status and the leptin axis in anorexic and recovered adolescents and young adults: a pilot study

    PubMed Central

    Zepf, F.D.; Sungurtekin, I.; Glass, F.; Elstrodt, L.; Peetz, D.; Hintereder, G.; Kratzsch, J.; Biskup, C.S.; Poustka, F.; Wöckel, L.

    2012-01-01

    Background Evidence from animal studies suggests that leptin metabolism is associated with zinc (Zn) status. However, research investigating this relationship in adolescents and young adults with anorexia nervosa (AN) is scarce; the present study aims to fill that gap. Methods Serum concentrations of leptin, the soluble leptin receptor (sOB-R) and the free leptin index (FLI) were obtained in healthy control subjects (n=19), acutely ill individuals (n=14) and recovered patients with AN (n=15). Serum Zn concentrations noted in previous research data were also incorporated for all groups. Results Leptin, FLI and Zn concentrations were higher in recovered subjects with AN when compared with acutely ill AN patients. Remitted patients showed higher sOB-R concentrations but no difference in FLI compared with the control group. Leptin and FLI were lower in the acutely ill patients compared with the control subjects, who showed no differences in Zn concentrations. Zn concentrations were not correlated with leptin, sOB-R or FLI concentrations in any of the three investigated subgroups. Conclusions The present investigation does not entirely support an association between Zn, Leptin and FLI concentrations in subjects with AN, possibly due to limited statistical power. Further research and replication of the present findings related to the interaction between leptin and Zn is warranted. However, with respect to serum leptin levels the data of the present investigation indicate that acutely ill and remitted patients with AN differ as regards serum leptin concentrations and FLI, which is in line with previous research. PMID:22393314

  12. Subcutaneous adipose tissue topography (SAT-Top) by means of the optical device lipometer highly correlated to plasma leptin levels in obese boys

    NASA Astrophysics Data System (ADS)

    Sudi, Karl; Moeller, Reinhard; Tafeit, Erwin; Reiterer, Elke; Borkenstein, Martin; Vrecko, Karoline; Horejsi, Renate; Reibnegger, Gilbert; Hofmann, Peter

    1998-05-01

    The product of the ob-gene named leptin is correlated with body fat mass in humans. Little evidence exists if the same holds true for body fat distribution. In this study we therefore investigated plasma leptin levels and the subcutaneous adipose tissue topography (SAT-Top) by means of the newly developed optical device Lipometer before and after a 3 week weight reduction camp. Thirty four obese boys (mean age 12a) took part in this study. Body fat distribution were assessed by means of Lipometer to measure the thickness of a subcutaneous fat layer at 15 standardized body sites (SAT- Top). Plasma leptin levels (LL) were measured by radioimmunoassay. All measurements were taken at the beginning and at the end of the camp. By dividing all boys according chronological age (group A: age less than 12a, n equals 17/group B: greater than 12a, n equals 17) we found correlations with the combination of measured body sites (MBS) before (A: MBS vs. LL, R2 equals 0.79; p less than 0.01/B: MBS vs. LL, R2 equals 0.35; n.s.) and after (A: MBS vs. LL, R2 equals 0.83; p less than 0.01/B: MBS vs. LL, R2 equals 0.70; p less than 0.01) the intervention. Our study confirms that the subcutaneous adipose tissue topography (SAT- Top) by means of the optical device Lipometer serves as a marker of plasma leptin levels in obese boys and highlights the use of this optical device in a predictive manner.

  13. Modulation of leptin resistance by food compounds.

    PubMed

    Aragonès, Gerard; Ardid-Ruiz, Andrea; Ibars, Maria; Suárez, Manuel; Bladé, Cinta

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. PMID:26842874

  14. Expression of leptin and its receptor genes in the ovarian follicles of cycling and early pregnant pigs.

    PubMed

    Smolinska, N; Kaminski, T; Siawrys, G; Przala, J

    2013-01-01

    Leptin is a polypeptide hormone produced primarily by adipocytes. It has been implicated in the regulation of satiety and energy homeostasis. Leptin has been suggested to play a role in reproduction based on its involvement in the regulation of the hypothalamic-pituitary-gonadal axis via endocrine, paracrine and/or autocrine pathways. The aim of the present study was to localize the cellular distribution of leptin and the long isoform of leptin receptor (OB-Rb) genes in porcine ovarian antral follicles and to compare the expression levels of leptin and OB-Rb mRNAs in porcine granulosa cells (GC), theca interna (TIC) and theca externa (TEC) cells during the luteal phase of the estrous cycle and in early pregnancy. The expression of leptin and OB-Rb genes was detected in GC, TIC and TEC. Significantly higher levels of leptin gene expression in GC were observed during the mid- and late-luteal phases of the cycle than on days 30 to 32 of pregnancy. On days 14 to 16 of pregnancy, leptin mRNA expression was higher than that on days 14 to 16 of the cycle. The expression of the OB-Rb gene in GC and TEC increased during pregnancy in comparison with the analyzed luteal phases of the cycle. Our results validate the hypothesis that locally produced leptin plays a role in the regulation of porcine reproduction at the ovarian level and exerts a direct effect on porcine follicles. The differences in OB-Rb gene expression in porcine GC and theca cells also suggest that their sensitivity to leptin varies in the ovaries of pregnant and cyclic pigs. PMID:23031202

  15. Leptin deficiency in maltreated children

    PubMed Central

    Danese, A; Dove, R; Belsky, D W; Henchy, J; Williams, B; Ambler, A; Arseneault, L

    2014-01-01

    Consistent with findings from experimental research in nonhuman primates exposed to early-life stress, children exposed to maltreatment are at high risk of detrimental physical health conditions, such as obesity and systemic inflammation. Because leptin is a key molecule involved in the regulation of both energy balance and immunity, we investigated abnormalities in leptin physiology among maltreated children. We measured leptin, body mass index and C-reactive protein in 170 12-year-old children members of the Environmental-Risk Longitudinal Twin Study, for whom we had prospectively-collected information on maltreatment exposure. We found that maltreated children exhibited blunted elevation in leptin levels in relation to increasing levels of physiological stimuli, adiposity and inflammation, compared with a group of non-maltreated children matched for gender, zygosity and socioeconomic status. These findings were also independent of key potential artifacts and confounders, such as time of day at sample collection, history of food insecurity, pubertal maturation and depressive symptoms. Furthermore, using birth weight as a proxy measure for leptin, we found that physiological abnormalities were presumably not present at birth in children who went on to be maltreated but only emerged over the course of childhood, after maltreatment exposure. Leptin deficiency may contribute to onset, persistence and progression of physical health problems in maltreated children. PMID:25247591

  16. Leptin and Atopic Dermatitis in Korean Elementary School Children.

    PubMed

    Seo, SungChul; Yoon, Won Suck; Cho, Yunjung; Park, Sang Hee; Choung, Ji Tae; Yoo, Young

    2016-04-01

    The prevalence of atopic dermatitis (AD) and obesity have been increasing considerably in Korean school-children. AD is a chronic pruritic recurrent inflammatory skin disorder. Leptin is secreted by adipocytes which has been suggested to be immunologically active; however, their role in AD has not yet been well understood. A total of 227 subjects out of 2,109 elementary school children were defined as having AD based on the ISAAC questionnaire survey. Ninety subjects with AD, aged between 6 and 12 years, completed scoring of severity of AD (SCORAD), skin prick testing, blood tests for total IgE, eosinophil counts, eosinophil cationic protein (ECP) and lipid profiles. Serum leptin levels were also measured. A subject with atopic AD was defined as an AD patient showing at least 1 positive reaction to allergens in skin prick testing. There were no significant differences in age, body mass index, percentage of breast milk feeding, mode of delivery, prevalence of atopy, and lipid profiles between atopic AD and non-atopic AD subjects. The serum leptin levels (log mean±SD) were significantly higher in non-atopic AD group than in the atopic AD group (0.86±0.57 ng/mL vs 0.53±0.72 ng/mL, p=0.045). Subjects with mild-to-moderate AD showed significantly higher serum leptin levels than those with severe AD (0.77±0.67 ng/mL vs 0.33±0.69 ng/mL, p=0.028). There was a marginal inverse correlation between the SCORAD index and the serum leptin concentration in total AD subjects (r=-0.216, p=0.053). The serum leptin levels were significantly higher in non-atopic AD subjects or mild-to-moderate AD subjects. Leptin did not seem to be associated with IgE-mediated inflammation in AD. Obesity-associated high leptin differed between non-atopic AD and atopic AD subjects. PMID:27090367

  17. Adipocyte iron regulates leptin and food intake

    PubMed Central

    Gao, Yan; Li, Zhonggang; Gabrielsen, J. Scott; Simcox, Judith A.; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T.; McClain, Donald A.

    2015-01-01

    Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

  18. Adipocyte iron regulates leptin and food intake.

    PubMed

    Gao, Yan; Li, Zhonggang; Gabrielsen, J Scott; Simcox, Judith A; Lee, Soh-hyun; Jones, Deborah; Cooksey, Bob; Stoddard, Gregory; Cefalu, William T; McClain, Donald A

    2015-09-01

    Dietary iron supplementation is associated with increased appetite. Here, we investigated the effect of iron on the hormone leptin, which regulates food intake and energy homeostasis. Serum ferritin was negatively associated with serum leptin in a cohort of patients with metabolic syndrome. Moreover, the same inverse correlation was observed in mice fed a high-iron diet. Adipocyte-specific loss of the iron exporter ferroportin resulted in iron loading and decreased leptin, while decreased levels of hepcidin in a murine hereditary hemochromatosis (HH) model increased adipocyte ferroportin expression, decreased adipocyte iron, and increased leptin. Treatment of 3T3-L1 adipocytes with iron decreased leptin mRNA in a dose-dependent manner. We found that iron negatively regulates leptin transcription via cAMP-responsive element binding protein activation (CREB activation) and identified 2 potential CREB-binding sites in the mouse leptin promoter region. Mutation of both sites completely blocked the effect of iron on promoter activity. ChIP analysis revealed that binding of phosphorylated CREB is enriched at these two sites in iron-treated 3T3-L1 adipocytes compared with untreated cells. Consistent with the changes in leptin, dietary iron content was also directly related to food intake, independently of weight. These findings indicate that levels of dietary iron play an important role in regulation of appetite and metabolism through CREB-dependent modulation of leptin expression. PMID:26301810

  19. Implications of leptin in neuroendocrine regulation of male reproduction.

    PubMed

    Landry, David; Cloutier, Frank; Martin, Luc J

    2013-03-01

    Obesity is a major health problem contributing to increased subfertility in males, as well as increased morbidity for diseases related to a decline in testosterone production with aging. Leptin is a hormone produced by adipose tissue whose production increases with the amount of body fat. Several studies have supported a relationship between increased leptin production and regulation of reproductive function. Indeed, leptin acts at all levels of the hypothalamus-pituitary-gonadal (HPG) axis in males. However, most of the obese individuals become insensitive to increased endogenous leptin production and develop a functional leptin resistance. This deregulation of leptin signaling might result in abnormal endocrine and reproductive functions. Altered leptin dynamics may contribute to male infertility in different ways, leading to hypogonadism. These include leptin resistance or leptin insufficiency at the hypothalamus and leptin modulation of testicular physiology. In this review, we address the mechanisms of action of leptin at different levels of the HPG axis. Moreover, the influences of leptin on steroidogenesis and spermatogenesis, as well as seasonal variations of leptin's action on male reproduction are discussed. PMID:23522066

  20. Expression of leptin and leptin receptor isoforms in the rat and human carotid body.

    PubMed

    Porzionato, Andrea; Rucinski, Marcin; Macchi, Veronica; Stecco, Carla; Castagliuolo, Ignazio; Malendowicz, Ludwik K; De Caro, Raffaele

    2011-04-18

    Leptin is known to play a role in the modulation of metabolism and control of breathing acting mainly on central nervous structures, although additional actions on peripheral arterial chemoreceptors have also been suggested in the literature. We therefore examined by means of immunohistochemistry the expression of leptin and leptin receptors in the carotid bodies of rats and humans. Leptin expression and relative expression of leptin receptor isoforms were also studied in rats by real-time PCR. No leptin or leptin receptor immunoreactivities were visible in the type II cells of either series. In rat carotid bodies, diffuse positive stainings for leptin and leptin receptors (both with antibody recognizing all receptor isoforms and antibody specific for Ob-Rb) were observed in type I cells. In human carotid bodies, the mean percentage (±standard error) of leptin immunoreactive type I cells was 39.4%±5.1% and the percentages of leptin receptor immunoreactive type I cells were 57.3%±3.9% with antibody recognizing all receptor isoforms and 33.3%±4.2% with antibody specific for isoform Ob-Rb. Double immunofluorescences with anti-tyrosine hydroxylase (type I cell marker) and anti-glial fibrillary acidic protein (type II cell markers) confirmed the selective location of leptin and Ob-Rb in type I cells. Real-time PCR showed the expression of leptin and Ob-Ra, Ob-Rb, Ob-Rc and Ob-Rf isoform mRNA in the rat carotid body, levels of expression being Ob-Rf>Ob-Rc>Ob-Ra>Ob-Rb. Ob-Re mRNA was not detected. The above findings suggest a role of circulating or locally produced leptin in the regulation of chemoreceptor discharge and/or metabolic sensing function, by means of direct action on type I cells. PMID:21334312

  1. Increased prepubertal body weight enhances leptin sensitivity in proopiomelanocortin and neuropeptide y neurons before puberty onset in female rats.

    PubMed

    Castro-González, David; Fuente-Martín, Esther; Sánchez-Garrido, Miguel A; Argente-Arizón, Pilar; Tena-Sempere, Manuel; Barrios, Vicente; Chowen, Julie A; Argente, Jesús

    2015-04-01

    Pubertal onset may be advanced by obesity, with leptin potentially acting as a permissive factor. We hypothesized that having increased body weight (BW) prepubertally affects the ability of leptin to activate intracellular signaling pathways and modulate the expression of hypothalamic neuropeptides involved in reproduction and metabolism. Because being raised in small litters (SLs) tends to increase BW at weaning, female rats were raised in litters of 4 or large litters (LLs) of 12 pups. Leptin (3 μg/g BW) or vehicle (saline) was injected sc at postnatal day (PND) 21 and 30. Rats raised in SLs weighed more at both ages, but relative visceral and subcutaneous fat was increased only on PND21. Serum leptin levels were not different at PND21 or PND30. At PND21, key elements of intracellular leptin signaling (phosphorylated signal transducer and activator of transcription 3 and phosphorylated Akt [p-Akt]) were lower in SL than in LL rats. Leptin injection stimulated phosphorylated signal transducer and activator of transcription 3 in both groups, with a greater increase in LL, whereas p-Akt rose only in SL rats. At PND30, basal leptin signaling did not differ between LL and SL rats. Leptin activation of Akt was similar at 45 minutes, but at 2 hours p-AKT levels were higher in SL than in LL rats, as was the decrease in neuropeptide Y mRNA and increase in pro-opiomelanocortin mRNA levels. No change in the reproductive axis was found. Thus, being raised in SLs increases BW and visceral body fat content, fails to increase plasma leptin concentrations, and increases the leptin responsiveness of both neuropeptide Y and pro-opiomelanocortin cells in the prepubertal hypothalamus. PMID:25574789

  2. The impact of leptin on perinatal development and psychopathology.

    PubMed

    Valleau, Jeanette C; Sullivan, Elinor L

    2014-11-01

    Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin's role and profile during development is examined in available human studies, and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where high leptin levels have been correlated

  3. THE INTAKE OF FIBER MESOCARP PASSIONFRUIT (PASSIFLORA EDULIS) LOWERS LEVELS OF TRIGLYCERIDE AND CHOLESTEROL DECREASING PRINCIPALLY INSULIN AND LEPTIN

    PubMed Central

    Corrêa, E.M.; Medina, L.; Barros-Monteiro, J.; Valle, N.O.; Sales, R.; Magalães, A.; Souza, F.C.A.; Carvalho, T.B.; Lemos, J.R.; Lira, E.F.; Lima, E.S.; Galeno, D.M.L.; Morales, L.; Ortiz, C.; Carvalho, R.P.

    2014-01-01

    Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease, renal failure, retinopathy, and neuropathy. Over the last years, there has been an increasing demand in folk medicine for natural sources that could help in the treatment of chronic diseases, including diabetes. The rind of passion fruit (Passiflora edulis f. Flavicarpa) is traditionally used as a functional food due to its high concentration of soluble and insoluble fiber. Objective The aim of this study was to determine the effect of high-fiber diet albedo of passion fruit on the metabolic and biochemical profile in diabetic rats induced by alloxan (2%). Design The passion fruit mesocarp fiber was dried in an oven with circulating air at 60°C and pulverized. We used 32 adult male rats, divided into 4 groups: Wistar group 1 control (GC), Wistar group 2, 15% fiber (GF15), Wistar group 3, 30% fiber (GF30), Wistar group 4, fiber disolved in water (GFH2O). The ratio of passion fruit was prepared according to the AIN 93M guidelines, varying only the source of dietary fiber. The corresponding diet for each group was offered to the animals for 60 days. Results There was a statically significant decrease in plasma glucose for GFH2O, GF15%, and GF30% groups with 27.0%, 37.4%, and 40.2%, respectively. Conclusion The use of mesocarp fiber of passion fruit at concentrations of 15% and 30% are an important dietary supplement for the treatment of DM due to its potential hypoglycemic effect, and its ability to reduce triglycerides and VLDL-cholesterol levels with a principal reduction of insulin and leptin. PMID:25346913

  4. Mismatch Amplification Mutation Assay Real-Time PCR Analysis of the Leptin Gene G2548A and A19G Polymorphisms and Serum Leptin in Infancy: A Preliminary Investigation.

    PubMed

    Savino, Francesco; Rossi, Lorenza; Di Stasio, Liliana; Galliano, Ilaria; Montanari, Paola; Bergallo, Massimiliano

    2016-01-01

    Leptin is a hormone that regulates food intake and energy metabolism. Its coding gene (LEP) is one of the most promising candidates for obesity. Although some studies have detected associations of different single nucleotide polymorphisms (SNPs) in the LEP gene with serum leptin levels and obesity-related traits, the results are still conflicting. We investigated two SNPs to find relationships with leptin concentrations. Thirty healthy Caucasian infants younger than 6 months were genotyped for the SNPs G2548A and A19G with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system-mismatch amplification mutation assay (ARMS- MAMA) real-time PCR, and serum leptin concentrations were measured with a radioimmunoassay method. Considering the significant linkage disequilibrium observed between the two SNPs, we divided the sample according to the number of GG haplotypes and observed that individuals homozygous for the GG haplotype had higher serum leptin levels in early infancy than the others. Although these preliminary results are based on a limited sample, they suggest that the genetic background seems to play a role in modulating leptin levels in infancy, but changes in leptin levels over infancy and their correlation with obesity need to be further explored. We describe an ARMS-MAMA real-time PCR procedure which could be profitably applied in routine genetic screening. PMID:27008407

  5. Leptin potentiates astrogenesis in the developing hypothalamus

    PubMed Central

    Rottkamp, Daniele M.; Rudenko, Ivan A.; Maier, Matthew T.; Roshanbin, Sahar; Yulyaningsih, Ernie; Perez, Luz; Valdearcos, Martin; Chua, Streamson; Koliwad, Suneil K.; Xu, Allison W.

    2015-01-01

    Background The proper establishment of hypothalamic feeding circuits during early development has a profound influence on energy homeostasis, and perturbing this process could predispose individuals to obesity and its associated consequences later in life. The maturation of hypothalamic neuronal circuitry in rodents takes place during the initial postnatal weeks, and this coincides with a dramatic surge in the circulating level of leptin, which is known to regulate the outgrowth of key neuronal projections in the maturing hypothalamus. Coincidently, this early postnatal period also marks the rapid proliferation and expansion of astrocytes in the brain. Methods Here we examined the effects of leptin on the proliferative capacity of astrocytes in the developing hypothalamus by treating postnatal mice with leptin. Mutant mice were also generated to conditionally remove leptin receptors from glial fibrillary acidic protein (GFAP)-expressing cells in the postnatal period. Results and conclusions We show that GFAP-expressing cells in the periventricular zone of the 3rd ventricle were responsive to leptin during the initial postnatal week. Leptin enhanced the proliferation of astrocytes in the postnatal hypothalamus and conditional removal of leptin receptors from GFAP-expressing cells during early postnatal period limited astrocyte proliferation. While increasing evidence demonstrates a direct role of leptin in regulating astrocytes in the adult brain, and given the essential function of astrocytes in modulating neuronal function and connectivity, our study indicates that leptin may exert its metabolic effects, in part, by promoting hypothalamic astrogenesis during early postnatal development. PMID:26629411

  6. Leptin signalling pathways in hypothalamic neurons.

    PubMed

    Kwon, Obin; Kim, Ki Woo; Kim, Min-Seon

    2016-04-01

    Leptin is the most critical hormone in the homeostatic regulation of energy balance among those so far discovered. Leptin primarily acts on the neurons of the mediobasal part of hypothalamus to regulate food intake, thermogenesis, and the blood glucose level. In the hypothalamic neurons, leptin binding to the long form leptin receptors on the plasma membrane initiates multiple signaling cascades. The signaling pathways known to mediate the actions of leptin include JAK-STAT signaling, PI3K-Akt-FoxO1 signaling, SHP2-ERK signaling, AMPK signaling, and mTOR-S6K signaling. Recent evidence suggests that leptin signaling in hypothalamic neurons is also linked to primary cilia function. On the other hand, signaling molecules/pathways mitigating leptin actions in hypothalamic neurons have been extensively investigated in an effort to treat leptin resistance observed in obesity. These include SOCS3, tyrosine phosphatase PTP1B, and inflammatory signaling pathways such as IKK-NFκB and JNK signaling, and ER stress-mitochondrial signaling. In this review, we discuss leptin signaling pathways in the hypothalamus, with a particular focus on the most recently discovered pathways. PMID:26786898

  7. Strategies for the delivery of leptin to the CNS.

    PubMed

    Banks, William A; Lebel, Carl R

    2002-06-01

    Leptin is the major regulator of body fat. It is a 16 kD protein released by fat cells into the blood and crosses the blood-brain barrier (BBB) to interact with its receptors at the arcuate nucleus to affect feeding, thermogenesis, and other functions. Within normal and obese body weight ranges, serum and cerebrospinal fluid (CSF) levels of leptin directly correlate with body mass index and adiposity. In animals, leptin at high levels exerts effects on appetite and at low levels informs the brain when fat reserves are adequate to switch behavioral, endocrine, and immune functions from starvation mode. Leptin offers a unique therapeutic opportunity for conditions related to body weight control, such as reversal of obesity and anorexia, and as an indirect treatment for diseases related to being over- or under-weight, such as insulin resistant diabetes and the endocrine changes accompanying starvation. In humans and in many rodent models, obesity may be a consequence of leptin resistance. More specifically, resistance likely results from an impaired transport of leptin across the BBB. Peripheral administration of native leptin results in weight reduction in moderately obese individuals and weight loss and reversal of insulin resistance and dyslipidemia in individuals with low leptin levels. The peripheral pharmacokinetic and BBB transport characteristics of native leptin suggests strategies for improving the therapeutic profile of leptin. These strategies include the development of longer lasting and more permeable analogs, development of antagonists, enhancing the activity of the leptin transporter, and delivering leptin by intrathecal administration. PMID:12164378

  8. Survivin upregulation, dependent on leptin-EGFR-Notch1 axis, is essential for leptin induced migration of breast carcinoma cells

    PubMed Central

    Knight, Brandi B.; Oprea-Ilies, Gabriela M.; Nagalingam, Arumugam; Yang, Lily; Cohen, Cynthia; Saxena, Neeraj K.; Sharma, Dipali

    2012-01-01

    Obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Molecular effects of obesity on carcinogenesis are mediated by autocrine and paracrine effects of adipocytokine leptin. Leptin participates in tumor progression and metastasis of human breast. We show that leptin induces clonogenicity and migration potential of breast cancer cells. We found that survivin expression is induced in response to leptin. In this study, we examine the role and leptin-mediated regulation of survivin. Leptin treatment leads to survivin upregulation, due in part to the activation of Notch1 and release of transcriptionally active Notch1-intracellular-domain (NICD). ChIP analysis show that NICD gets recruited to survivin promoter at CSL-binding-site in response to leptin treatment. Inhibition of Notch1 activity inhibits leptin-induced survivin upregulation. Leptin-induced transactivation of EGFR is involved in leptin-mediated Notch1 and survivin upregulation showing a novel upstream role of leptin-EGFR-Notch1 axis. We further show that leptin-induced migration of breast cancer cells requires survivin, as overexpression of survivin further increases, whereas silencing survivin abrogates leptin-induced migration. Using a pharmacological approach to inhibit survivin, we show that 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase inhibitors (HRIs), lovastatin, can effectively inhibit leptin-induced survivin expression and migration. Importantly, leptin increased breast tumor growth in nude mice. These data show a novel role for survivin in leptin-induced migration and put forth pharmacological survivin inhibition as a potential novel therapeutic target. This conclusion is supported by in vivo data showing overexpression of leptin and survivin in epithelial cells of high grade ductal carcinoma in situ and high grade invasive carcinoma. PMID:21555376

  9. C-Reactive Protein Modifies the Association of Plasma Leptin With Coronary Calcium in Asymptomatic Overweight Individuals

    PubMed Central

    Martin, Seth S.; Qasim, Atif N.; Rader, Dan J.; Reilly, Muredach P.

    2014-01-01

    Evidence suggests putative interactions of leptin and C-reactive protein (CRP) in the pathogenesis of adiposity-related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community-based cross-sectional studies coordinated at a single, university-based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log-transformed plasma leptin levels with higher CRP levels as defined by three cut-points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex-specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut-point (interaction term P values all <0.01 in fully adjusted models). Leptin levels were associated with CAC in those with high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in ln(leptin) (95% CI): 2.18 (1.29–3.66) if CRP level ≥3 mg/l; N = 461 vs. 0.94 (0.67–1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin-CRP interface in atherosclerosis risk. PMID:21738237

  10. Metformin increases hepatic leptin receptor and decreases steatosis in mice.

    PubMed

    Tang, Xuemei; Li, Jingwen; Xiang, Wei; Cui, Ye; Xie, Bin; Wang, Xiaodong; Xu, Zihui; Gan, Lixia

    2016-08-01

    In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying these effects are still incompletely understood. Emerging evidence suggest metformin as leptin sensitizer to mediate the weight-loss effect in the brain. In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5months. Afterward, mice were treated with metformin (50mg/kg or 200mg/kg) for 15days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dose-dependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis. PMID:27288055

  11. Gut Microbiota Composition in Male Rat Models under Different Nutritional Status and Physical Activity and Its Association with Serum Leptin and Ghrelin Levels

    PubMed Central

    Queipo-Ortuño, María Isabel; Seoane, Luisa María; Murri, Mora; Pardo, María; Gomez-Zumaquero, Juan Miguel; Cardona, Fernando; Casanueva, Felipe; Tinahones, Francisco J.

    2013-01-01

    Background Several evidences indicate that gut microbiota is involved in the control of host energy metabolism. Objective To evaluate the differences in the composition of gut microbiota in rat models under different nutritional status and physical activity and to identify their associations with serum leptin and ghrelin levels. Methods In a case control study, forty male rats were randomly assigned to one of these four experimental groups: ABA group with food restriction and free access to exercise; control ABA group with food restriction and no access to exercise; exercise group with free access to exercise and feed ad libitum and ad libitum group without access to exercise and feed ad libitum. The fecal bacteria composition was investigated by PCR-denaturing gradient gel electrophoresis and real-time qPCR. Results In restricted eaters, we have found a significant increase in the number of Proteobacteria, Bacteroides, Clostridium, Enterococcus, Prevotella and M. smithii and a significant decrease in the quantities of Actinobacteria, Firmicutes, Bacteroidetes, B. coccoides-E. rectale group, Lactobacillus and Bifidobacterium with respect to unrestricted eaters. Moreover, a significant increase in the number of Lactobacillus, Bifidobacterium and B. coccoides–E. rectale group was observed in exercise group with respect to the rest of groups. We also found a significant positive correlation between the quantity of Bifidobacterium and Lactobacillus and serum leptin levels, and a significant and negative correlation among the number of Clostridium, Bacteroides and Prevotella and serum leptin levels in all experimental groups. Furthermore, serum ghrelin levels were negatively correlated with the quantity of Bifidobacterium, Lactobacillus and B. coccoides–Eubacterium rectale group and positively correlated with the number of Bacteroides and Prevotella. Conclusions Nutritional status and physical activity alter gut microbiota composition affecting the diversity and

  12. The Impact of Leptin on Perinatal Development and Psychopathology

    PubMed Central

    Valleau, Jeanette C.; Sullivan, Elinor L.

    2014-01-01

    Leptin has long been associated with metabolism as it is a critical regulator of both food intake and energy expenditure, but recently, leptin dysregulation has been proposed as a mechanism of psychopathology. This review discusses the evidence supporting a role for leptin in mental health disorders and describes potential mechanisms that may underlie this association. Leptin plays a critical role in pregnancy and in fetal growth and development. Leptin’s role and profile during development is examined in available human studies and the validity of applying studies conducted in animal models to the human population are discussed. Rodents experience a postnatal leptin surge, which does not occur in humans or larger animal models. This suggests that further research using large mammal models, which have a leptin profile across pregnancy and development similar to humans, are of high importance. Maternal obesity and hyperleptinemia correlate with increased leptin levels in the umbilical cord, placenta, and fetus. Leptin levels are thought to impact fetal brain development; likely by activating proinflammatory cytokines that are known to impact many of the neurotransmitter systems that regulate behavior. Leptin is likely involved in behavioral regulation as leptin receptors are widely distributed in the brain, and leptin influences cortisol release, the mesoaccumbens dopamine pathway, serotonin synthesis, and hippocampal synaptic plasticity. In humans, both high and low levels of leptin are reported to be associated with psychopathology. This inconsistency is likely due to differences in the metabolic state of the study populations. Leptin resistance, which occurs in the obese state, may explain how both high and low levels of leptin are associated with psychopathology, as well as the comorbidity of obesity with numerous mental illnesses. Leptin resistance is likely to influence disorders such as depression and anxiety where both high and low leptin levels have been

  13. Leptin links with plasminogen activator inhibitor-1 in human obesity: the SABPA study.

    PubMed

    Pieterse, Chiné; Schutte, Rudolph; Schutte, Aletta E

    2015-07-01

    The relationship between obesity and the development of cardiovascular disease is well established. However, the underlying mechanisms contributing to vascular disease and increased cardiovascular risk in the obese remain largely unexplored. Since leptin exerts direct vascular effects, we investigated leptin and the relationship thereof with circulating markers of vascular damage, namely plasminogen activator inhibitor-1 antigen (PAI-1(ag)), von Willebrand factor antigen (vWF(ag)) and urinary albumin-to-creatinine ratio (ACR). The study included a bi-ethnic population of 409 African and Caucasian teachers who were stratified into lean (<0.5) and obese (⩾0.5) groups according to waist-to-height ratio. We obtained ambulatory blood pressure measurements and determined serum leptin levels, PAI-1(ag), vWF(ag) and ACR, as markers of vascular damage. The obese group had higher leptin (P<0.001) and PAI-1(ag) (P<0.001) levels and a tendency existed for higher vWF(ag) (P=0.068). ACR did not differ between the two groups (P=0.21). In single regression analyses positive associations existed between leptin and all markers of vascular damage (all P<0.001) only in the obese group. After adjusting for covariates and confounders in multiple regression analyses, only the association between leptin and PAI-1(ag) remained (R(2)=0.440; β=0.293; P=0.0021). After adjusting for gender, ethnicity and age, additional analyses indicated that leptin also associated with fibrinogen and clot lysis time in both lean and obese groups, which in turn is associated with 24- h blood pressure and pulse pressure. This result provides evidence that elevated circulating leptin may directly contribute to vascular damage, possibly through mechanism related to thrombotic vascular disease. PMID:25740294

  14. NEWS: Help for the higher level

    NASA Astrophysics Data System (ADS)

    2000-03-01

    January 2000 saw the instigation of a network of subject centres to promote high quality learning and teaching practices in universities and colleges throughout the UK. A total of £30m has been committed over five years by the four funding bodies for UK higher education to this Learning and Teaching Support Network (LTSN). The network will consist of 24 subject centres, each hosted by a university or college, plus a Generic Learning and Teaching Centre based in York (as part of the new Institute for Learning and Teaching). The latter centre will give advice on issues that affect higher education as a whole - such as the use of information technology. Among the tasks for the subject centres will be: the collation and promotion of information on good practice; the promotion of computing and IT approaches to teaching, learning and assessment; the provision of opportunities for professional development; and the maintenance of working relationships with professional bodies both in the UK and internationally. The subject centre for the Physical Sciences will be at the University of Hull (contact Dr Tina Overton, tel: 01482 465 453) with Engineering at Loughborough, Materials at Liverpool, Medicine at Newcastle, Mathematics, Statistics and Operational Research at Birmingham. The first annual conference of the Institute for Learning and Teaching in Higher Education is planned for 27 - 29 June at the College of Ripon and York St John. More details of this and the other events organized by the Institute can be obtained from ILT, Genesis 3, Innovation Way, York Science Park, Heslington, York YO10 5DQ (tel: 01904 434222, enquiries@ilt.ac.uk or www.ilt.ac.uk ).

  15. The Effects of Leptin on Breastfeeding Behaviour.

    PubMed

    Cannon, Anna M; Kakulas, Foteini; Hepworth, Anna R; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T

    2015-10-01

    Breastfed infants have a reduced risk of becoming overweight and/or obese later in life. This protective effect has been partly attributed to leptin present in breastmilk. This study investigated 24-h variations of skim milk leptin and its relationship with breastmilk macronutrients and infant breastfeeding patterns. Exclusive breastfeeding mothers of term singletons (n = 19; age 10 ± 5 weeks) collected pre- and post-feed breastmilk samples for every breastfeed over a 24-h period and test-weighed their infants to determine milk intake at every breastfeed over a 24-h period. Samples (n = 454) were analysed for leptin, protein, lactose and fat content. Skim milk leptin concentration did not change with feeding (p = 0.184). However, larger feed volumes (>105 g) were associated with a decrease in post-feed leptin levels (p = 0.009). There was no relationship between the change in leptin levels and change in protein (p = 0.313) or lactose levels (p = 0.587) between pre- and post-feed milk, but there was a trend for a positive association with changes in milk fat content (p = 0.056). Leptin concentration significantly increased at night (p < 0.001) indicating a possible 24-h pattern. Leptin dose (ng) was not associated with the time between feeds (p = 0.232). Further research should include analysis of whole breastmilk and other breastmilk fractions to extend these findings. PMID:26437426

  16. Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women

    PubMed Central

    Rizk, Nasser M.; Sharif, Elham

    2015-01-01

    Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin. PMID:26180527

  17. Site-specific circadian expression of leptin and its receptor in human adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian variability of circulating leptin levels has been well established over the last decade. However, the circadian behavior of leptin in human adipose tissue remains unknown. This also applies to the soluble leptin receptor. We investigated the ex vivo circadian behavior of leptin and its rec...

  18. [Leptin and hypothalamus-hypophysis-thyroid axis].

    PubMed

    Riccioni, G; Menna, V; Lambo, M S; Della Vecchia, R; Di Ilio, C; De Lorenzo, A; D'Orazio, N

    2004-01-01

    The leptin system is a major regulator of food intake and metabolic rate. The leptin, an adipose tissue hormone whose plasma levels reflect energy stores, plays an important rule in the pathogenesis of such eating disorders like bulimia and anorexia. Thyroid hormones are major regulators of energy homeostasis. It is possible that leptin and thyroid hormone exert their actions on thermogenesis and energy metabolism via the same common effector patways. Leptin influences feedback regulation of the hypotalamic TRH-secreting neurons by thyroid hormone. Low serum levels of thyroid hormones reflect a dysfunction of the hypotalamic-pituitary-thyroid (HPT) and hypotalamic-pituitary-adrenal (HPA) axis in patients with nervosa anorexia. Neuroendocrine effects of leptin include effects on the HPT and HPA axis. The aim of this work is to evaluated the interactions between leptina and HPT axis on the basis of recent published works and reviews in literature. PMID:15147079

  19. GLUCOMANNAN AND GLUCOMANNAN PLUS SPIRULINA-ENRICHED SQUID-SURIMI ADDED TO HIGH SATURATED DIET AFFECT GLYCEMIA, PLASMA AND ADIPOSE LEPTIN AND ADIPONECTIN LEVELS IN GROWING FA/FA RATS.

    PubMed

    Vázquez-Velasco, Miguel; González-Torres, Laura; Méndez, María Teresa; Bastida, Sara; Benedí, Juana; González-Muñoz, M José; Sánchez-Muniz, Francisco J

    2015-01-01

    Type 2 diabetes is a very prevalent chronic disease. Among dietary factors for its prevention and treatment, interest has grown in satiating fibre (konjac glucomannan) and spirulina. Our previous studies suggest that glucomannan itself and/or in conjunction to spirulina displayed hypolipemic and antioxidant effects when incorporated to squid surimi as functional ingredients. The present study aims to determine whether glucomannan- enriched or glucomannan plus spirulina-enriched squid-surimi improve plasma glucose and insulin levels in Zucker fa/fa rats fed a high saturated fat diet. Twenty four growing rats, divided into three groups, were given modified AIN-93M diets for seven weeks: 30% squid-surimi control diet (C), 30% glucomannan-enriched squid-surimi diet (G) and 30% glucomannan plus spirulina-enriched squid-surimi diet (GS). All rats became hyperglycemics and hyperinsulinemics, but G and GS diets induced significantly lower glucose levels (20%; p < 0.05) but did not modify insulinemia with respect to C diet. GS animals showed higher HOMA-D (p < 0.05) than C ones suggesting increased insulin availability. Plasma leptin and adiponectin decreased in G and GS vs. C group (p < 0.05). Adipose adiponectin increased significantly in G and GS vs. C rats (16-20 times, p < 0.01). Leptin in adipose tissue was higher in GS vs. G group (p < 0.05). In conclusion, both glucomannan-diets were able to reduce hyperglycemia and increase adipose tissue adiponectin levels in fa/fa rats, suggesting an anti-hypertrophic and insulin-sensitizing adipokine effect in this tissue. Spirulina inclusion increased insulin availability. Although results are promising, the utility of consuming glucomannan surimis as part of usual diets demands future studies. PMID:26667726

  20. 20 years of leptin: role of leptin in human reproductive disorders.

    PubMed

    Chou, Sharon H; Mantzoros, Christos

    2014-10-01

    Leptin, as a key hormone in energy homeostasis, regulates neuroendocrine function, including reproduction. It has a permissive role in the initiation of puberty and maintenance of the hypothalamic-pituitary-gonadal axis. This is notable in patients with either congenital or acquired leptin deficiency from a state of chronic energy insufficiency. Hypothalamic amenorrhea is the best-studied, with clinical trials confirming a causative role of leptin in hypogonadotropic hypogonadism. Implications of leptin deficiency have also emerged in the pathophysiology of hypogonadism in type 1 diabetes. At the other end of the spectrum, hyperleptinemia may play a role in hypogonadism associated with obesity, polycystic ovarian syndrome, and type 2 diabetes. In these conditions of energy excess, mechanisms of reproductive dysfunction include central leptin resistance as well as direct effects at the gonadal level. Thus, reproductive dysfunction due to energy imbalance at both ends can be linked to leptin. PMID:25056118

  1. Leptin concentrations in the follicular phase of spontaneous cycles and cycles superovulated with follicle stimulating hormone.

    PubMed

    Messinis, I E; Milingos, S; Zikopoulos, K; Kollios, G; Seferiadis, K; Lolis, D

    1998-05-01

    It has been reported that oestradiol may play a role in the production of leptin from adipocytes. To investigate this relationship further, nine normally ovulating women were studied during two menstrual cycles, i.e. an untreated spontaneous cycle and a cycle treated with follicle stimulating hormone (FSH) from cycle day 2 until the day of human chorionic gonadotrophin (HCG) injection. Serum leptin values on cycle day 2 did not differ significantly between the spontaneous and the FSH cycles. In the spontaneous cycles, leptin values declined gradually and significantly up to day 7 and then increased progressively up to the day of luteinizing hormone (LH) surge onset, at which point they achieved the highest values. In the FSH cycles, serum leptin values increased gradually and significantly up to day 6, remaining stable thereafter, and were in the midfollicular phase significantly higher than in the spontaneous cycles. Significant positive correlations were found between mean values of leptin and mean values of oestradiol during the second half of the follicular phase in the spontaneous cycles and during the first half in the FSH cycles. A significant negative correlation was found between these two parameters in the spontaneous cycles during the first half of the follicular phase. Serum leptin levels were significantly higher in the midluteal than in the follicular phase in both cycles. These results demonstrate for the first time significant changes in leptin values during the follicular phase of the human menstrual cycle and a significant increase during superovulation induction with FSH. It is suggested that oestradiol may be involved in the regulation of leptin production in women. PMID:9647537

  2. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    PubMed

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain. PMID

  3. Leptin: a novel therapeutic strategy for Alzheimer's disease.

    PubMed

    Tezapsidis, Nikolaos; Johnston, Jane M; Smith, Mark A; Ashford, J Wesson; Casadesus, Gemma; Robakis, Nikolaos K; Wolozin, Benjamin; Perry, George; Zhu, Xiongwei; Greco, Steven J; Sarkar, Sraboni

    2009-01-01

    Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin has been shown to reduce the amount of extracellular amyloid beta, both in cell culture and animal models, as well as to reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models. In AD, weight loss often precedes the onset of dementia and the level of circulating leptin is inversely proportional to the severity of cognitive decline. It is speculated that a deficiency in leptin levels or function may contribute to systemic and CNS abnormalities leading to disease progression. Furthermore, a leptin deficiency may aggravate insulin-controlled pathways, known to be aberrant in AD. These observations suggest that a leptin replacement therapy may be beneficial for these patients. PMID:19387109

  4. Gender-dependent differences in serum profiles of insulin and leptin in caloric restricted rats.

    PubMed

    Guevara, R; Valle, A; Gianotti, M; Roca, P; Oliver, J

    2008-01-01

    In the present study, we have investigated whether differences between male and female rats described in response to 40% caloric restriction (CR) were influenced by circulating level variations of sex hormones and/or insulin and leptin. Body weights (BW), organ weights, and adipose depot weights (ADW) were also measured. The most affected tissues by CR were the fat depots. Metabolically active organs were the least affected, especially more in females than in males (male weight lost: 24.3% vs. female: 17.3%). Testosterone and estradiol circulating levels did not show changes by CR. Insulin levels were decreased by CR in both genders, but was more evident in female rats than males. Leptin serum levels were higher in male rats than in females, and CR caused a circulating leptin level reduction only in males. In conclusion, our results indicate that leptin and insulin could be one of the keys of the different hormonal control of energy homeostasis in response to CR between female and male rats. In this sense, leptin serum levels correlated statistically with BW and with individual ADW only in male rats, whereas insulin serum levels correlated statistically with BW and with any of the ADW studied only in females. PMID:18176912

  5. Leptin production and release in the dually in vitro perfused human placenta.

    PubMed

    Linnemann, K; Malek, A; Sager, R; Blum, W F; Schneider, H; Fusch, C

    2000-11-01

    There is clear evidence that the placenta produces leptin. However, it is still unclear to what extent leptin is released into the maternal and the fetal circulation. The aim of our study was to determine placental leptin release rates into these 2 compartments. In 10 term placentas, using dual in vitro perfusion of an isolated cotyledon, concentrations of leptin, hCG, and human placental lactogen (hPL) were determined in perfusates and in the tissue before and after perfusion. With perfusions lasting 270-840 min, total leptin production was 225 pg/g x min [median; interquartile range (IQR), 76-334 pg/g x min]. The release into the fetal circulation was very low (median, 2.5; IQR, 1.1-5.9 pg/g x min) compared with the release into the maternal circulation (median, 203; IQR, 79-373 pg/g x min) corresponding to 1.6% and 98.4% of net release. Only 0.05% of hPL and hCG were released into the fetal circulation and 99.95% into the maternal circulation, confirming previous results. Release into the fetal circulation correlated significantly with release into the maternal circulation for leptin (r = 0.648; P < 0.05) and hPL (r = 0.721; P < 0.05). Furthermore, release of leptin into the fetal circulation was positively correlated with release of fetal hCG (r = 0.661; P < 0.05). Most of the leptin produced by the placenta is released into the maternal circulation, but compared with other placental hormones (hCG and hPL), a considerably higher proportion of leptin is released into the fetal circulation. These findings may at least partially explain the marked increase in maternal serum leptin levels in pregnancy. The rapid postnatal decrease in leptin levels in both the mother and the neonate is also consistent with the concept of placental origin. PMID:11095471

  6. Plasma leptin in non-diabetic Asian Indians: association with abdominal adiposity.

    PubMed

    Ramachandran, A; Snehalatha, C; Vijay, V; Satyavani, K; Latha, E; Haffner, S M

    1997-11-01

    Plasma leptin concentrations were measured in 144 non-diabetic men and women (age 21-73 years, BMI 14.8-37.7 kg m(-2)), in fasting samples collected during a population survey for diabetes mellitus. Leptin, fasting and 2-h post-glucose load plasma concentrations of glucose and immunoreactive insulin were measured. In a subset of 50 normoglycaemic individuals, subcutaneous fat (SF) and visceral fat (VF) areas at L4-L5 level were also measured by CT. As in other populations, women had significantly higher plasma leptin concentrations than men (p < 0.001) but the values were similar in normal (NGT) and impaired glucose tolerance (IGT). Geometric mean concentrations of leptin in men and women with NGT were 4.8 and 17.7 ng ml(-1), respectively, and the corresponding values in IGT were 6.2 and 19.0 ng ml(-1). Multiple regression analysis in the total group showed that the leptin concentration (log-transformed) was strongly dependent on sex (R2 = 53.4%), BMI (R2 = 17.4%), and to a lesser degree on the 2-h plasma insulin (R2 = 2.4%) and the WHR (R2 = 0.8%). In men, the total abdominal fat showed a strong association with leptin (R2 = 49.3%) and in women the subcutaneous fat area showed a similar effect (R2 = 39.5%). It is likely that subcutaneous and not visceral fat may be a determinant of plasma leptin in Asian Indians, and the correlation between leptin and insulin resistance may be less strong than in other ethnic groups. PMID:9400917

  7. The Role of BDNF, Leptin, and Catecholamines in Reward Learning in Bulimia Nervosa

    PubMed Central

    Grob, Simona; Milos, Gabriella; Schnyder, Ulrich; Eckert, Anne; Lang, Undine; Hasler, Gregor

    2015-01-01

    Background: A relationship between bulimia nervosa and reward-related behavior is supported by several lines of evidence. The dopaminergic dysfunctions in the processing of reward-related stimuli have been shown to be modulated by the neurotrophin brain derived neurotrophic factor (BDNF) and the hormone leptin. Methods: Using a randomized, double-blind, placebo-controlled, crossover design, a reward learning task was applied to study the behavior of 20 female subjects with remitted bulimia nervosa and 27 female healthy controls under placebo and catecholamine depletion with alpha-methyl-para-tyrosine (AMPT). The plasma levels of BDNF and leptin were measured twice during the placebo and the AMPT condition, immediately before and 1 hour after a standardized breakfast. Results: AMPT–induced differences in plasma BDNF levels were positively correlated with the AMPT–induced differences in reward learning in the whole sample (P=.05). Across conditions, plasma brain derived neurotrophic factor levels were higher in remitted bulimia nervosa subjects compared with controls (diagnosis effect; P=.001). Plasma BDNF and leptin levels were higher in the morning before compared with after a standardized breakfast across groups and conditions (time effect; P<.0001). The plasma leptin levels were higher under catecholamine depletion compared with placebo in the whole sample (treatment effect; P=.0004). Conclusions: This study reports on preliminary findings that suggest a catecholamine-dependent association of plasma BDNF and reward learning in subjects with remitted bulimia nervosa and controls. A role of leptin in reward learning is not supported by this study. However, leptin levels were sensitive to a depletion of catecholamine stores in both remitted bulimia nervosa and controls. PMID:25522424

  8. Effect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus

    PubMed Central

    Jamalan, Mostafa; Rezazadeh, Mahin; Zeinali, Majid; Ghaffari, Mohammad Ali

    2015-01-01

    Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of high-sensitivity C-reactive protein (hs-CRP), insulin, leptin, tumor necrosis factor alpha (TNF-α), and serum amyloid A (SAA) in patients with diabetes mellitus type 2. Materials and Methods: Male patients (n=80) were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day) or alpha-tocopherol (300 mg/day) orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared. Results: Our results showed that both ascorbic acid and alpha-tocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alpha-tocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level. Conclusion: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2. It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus. PMID:26693410

  9. The Effects of Leptin Replacement on Neural Plasticity

    PubMed Central

    Paz-Filho, Gilberto J.

    2016-01-01

    Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID:26881138

  10. Leptin as a modulator of neuroendocrine function in humans.

    PubMed

    Khan, Sami M; Hamnvik, Ole-Petter R; Brinkoetter, Mary; Mantzoros, Christos S

    2012-07-01

    Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

  11. Leptin as a Modulator of Neuroendocrine Function in Humans

    PubMed Central

    Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

    2012-01-01

    Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

  12. Fibroblast Growth Factor 21 Levels in Young Healthy Females Display Day and Night Variations and Are Increased in Response to Short-Term Energy Deprivation Through a Leptin-Independent Pathway

    PubMed Central

    Foo, Joo-Pin; Aronis, Konstantinos N.; Chamberland, John P.; Paruthi, Jason; Moon, Hyun-Seuk; Mantzoros, Christos S.

    2013-01-01

    OBJECTIVE Fibroblast growth factor (FGF)-21 is an endocrine factor with potent metabolic effects. Its day–night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated. We aim to elucidate day–night pattern of FGF-21 levels and its relationship to FFA, to assess whether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes. RESEARCH DESIGN AND METHODS Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 a.m. on day 4 until 8:00 a.m. on day 5. RESULTS FGF-21 exhibited day–night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day–night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states. CONCLUSIONS A day–night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close cross-correlations with FFA in both fed state and energy deprivation, needs to be studied further. PMID:23193213

  13. Leptin and its receptor in hematologic malignancies

    PubMed Central

    Han, Tian-Jie; Wang, Xin

    2015-01-01

    Leptin is an adipocyte-derived cytokine coded by the obese gene, not only regulates metabolism, but also participates in hematopoiesis. Aberrant leptin levels in patients with hematologic malignancies were observed and associates with clinical characters, such as body mass index (BMI), gender, blast cell percentage. Leptin concentrations alter while diseases progress or remission. Leptin receptor is expressed in hematopoietic CD34+ stem cells, erythrocytes, lymphocytes, blast cells and samples in leukemia and lymphoma patients. The adipokine stimulates cell proliferation, cytokine secretion and protects malignant cells from apoptosis through Janus kinase-signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase and extracellular signal activated kinase 1/2 (MAPK/ERK1/2), or 3 kinase (PI3K) signaling pathways. These findings indicate leptin signaling possibility take part in occurrence, progression and prognosis of hematologic malignancies. This article reviews leptin/leptin receptor expression and the correlations with clinical characters, treatment and prognosis in myeloid and lymphoid neoplasms. PMID:26884894

  14. Leptin inhibits testosterone secretion from adult rat testis in vitro.

    PubMed

    Tena-Sempere, M; Pinilla, L; González, L C; Diéguez, C; Casanueva, F F; Aguilar, E

    1999-05-01

    Leptin, the product of the ob gene, has emerged recently as a pivotal signal in the regulation of fertility. Although the actions of leptin in the control of reproductive function are thought to be exerted mainly at the hypothalamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we first assessed the ability of leptin to regulate testicular testosterone secretion in vitro. Secondly, we aimed to evaluate whether leptin can modulate basal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from prepubertal and adult rats were incubated with increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular responsiveness to leptin may be dependent on the background leptin levels, testicular tissue from both food-deprived and normally-fed animals was used. Furthermore, leptin modulation of stimulated testosterone secretion was evaluated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, analysis of leptin actions on pituitary function was carried out using hemi-pituitaries from fasted adult male rats incubated in the presence of increasing concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testosterone levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal and adult male rats. However, a significant reduction in circulating LH levels was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin had no effect on basal or hCG-stimulated testosterone secretion by testes from prepubertal rats, regardless of the nutritional state of the donor animal. In contrast, leptin significantly decreased basal and hCG-induced testosterone secretion by testes from fasted and fed

  15. Relationship between Serum Leptin, Ghrelin and Dietary Macronutrients in Women with Polycystic Ovary Syndrome

    PubMed Central

    Pourghassem Gargari, Bahram; Houjeghani, Shiva; Farzadi, Laya; Houjeghani, Sheyda; Safaeiyan, Abdolrasoul

    2015-01-01

    Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women. It may involve an impairment in physiologic regulation of leptin and ghrelin. There is limited, controversial data on the relation of dietary components with leptin and ghrelin in PCOS, so the current study has been conducted to explore the effects of different macronutrients on serum levels of leptin and ghrelin in PCOS and healthy subjects. Materials and Methods In this case-control study, we randomly choose 30 PCOS pa- tients and 30 healthy age and body mass index (BMI) matched controls. Intake of macronutrients [protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids (PUFA), carbohydrate, dietary fiber] and energy were assessed using 3-day, 24-hour food recall and food frequency questionnaires (FFQ). Fasting hormonal status was measured for each participant. Results PCOS women had higher levels of serum leptin, insulin, testosterone, and luteinizing hormone (LH), whereas sex hormone-binding globulin (SHBG) was lower compared to healthy women. There was no significant difference in mean ghrelin concentrations between the groups. Among PCOS women, independent of BMI and total energy intake, we observed an inverse association between leptin concentration and total dietary fat (β=-0.16, P<0.05) and saturated fatty acid (SFA) intake (β=-0.58, P<0.05). This relationship was not seen in the healthy subjects. There was no significant association between ghrelin and macronutrients in PCOS and healthy participants. Conclusion Certain habitual dietary components such as fat and SFA may decrease serum leptin, whereas ghrelin is not influenced by these in PCOS women. More studies are needed to better clarify the effects of dietary macronutrients on serum leptin and ghrelin. PMID:26644854

  16. Lean heart: Role of leptin in cardiac hypertrophy and metabolism.

    PubMed

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-09-26

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  17. Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns.

    PubMed

    Allard, C; Desgagné, V; Patenaude, J; Lacroix, M; Guillemette, L; Battista, M C; Doyon, M; Ménard, J; Ardilouze, J L; Perron, P; Bouchard, L; Hivert, M F

    2015-01-01

    Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (β = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10(-11); N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (β = -0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (β = -0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation. PMID:25800063

  18. Leptin-based Adjuvants: An Innovative Approach to Improve Vaccine Response

    PubMed Central

    White, Sarah J.; Taylor, Matthew J.; Hurt, Ryan; Jensen, Michael D.; Poland, Gregory A.

    2013-01-01

    Leptin is a pleiotropic hormone with multiple direct and regulatory immune functions. Leptin deficiency or resistance hinders the immunologic, metabolic, and neuroendocrinologic processes necessary to thwart infections and their associated complications, and to possibly protect against infectious diseases following vaccination. Circulating leptin levels are proportional to body fat mass. High circulating leptin concentrations, as observed in obesity, are indicative of the development of leptin transport saturation/signaling desensitization. Leptin bridges nutritional status and immunity. Although its role in vaccine response is currently unknown, over-nutrition has been shown to suppress vaccine-induced immune responses. For instance, obesity (BMI ≥ 30 kg/m2) is associated with lower antigen-specific antibody titers following influenza, hepatitis B, and tetanus vaccinations. This suggests that obesity, and possibly saturable leptin levels, are contributing factors to poor vaccine immunogenicity. While leptin-based therapies have not been investigated as vaccine adjuvants thus far, leptin’s role in immunity suggests that application of these therapies is promising and worth investigation to enhance vaccine response in people with leptin signaling impairments. This review will examine the possibility of using leptin as a vaccine adjuvant by: briefly reviewing the distribution and signal transduction of leptin and its receptors; discussing the physiology of leptin with emphasis on its immune functions; reviewing the causes of attenuation of leptin signaling; and finally, providing plausible inferences for the innovative use of leptin-based pharmacotherapies as vaccine adjuvants. PMID:23370154

  19. Taste Responsiveness to Sweeteners Is Resistant to Elevations in Plasma Leptin

    PubMed Central

    Elson, Amanda E.T.; Kalik, Salina; Sosa, Yvett; Patterson, Christa M.; Myers, Martin G.; Munger, Steven D.

    2015-01-01

    There is uncertainty about the relationship between plasma leptin and sweet taste in mice. Whereas 2 studies have reported that elevations in plasma leptin diminish responsiveness to sweeteners, another found that they enhanced responsiveness to sucrose. We evaluated the impact of plasma leptin on sweet taste in C57BL/6J (B6) and leptin-deficient ob/ob mice. Although mice expressed the long-form leptin receptor (LepRb) selectively in Type 2 taste cells, leptin failed to activate a critical leptin-signaling protein, STAT3, in taste cells. Similarly, we did not observe any impact of intraperitoneal (i.p.) leptin treatment on chorda tympani nerve responses to sweeteners in B6 or ob/ob mice. Finally, there was no effect of leptin treatment on initial licking responses to several sucrose concentrations in B6 mice. We confirmed that basal plasma leptin levels did not exceed 10ng/mL, regardless of time of day, physiological state, or body weight, suggesting that taste cell LepRb were not desensitized to leptin in our studies. Furthermore, i.p. leptin injections produced plasma leptin levels that exceeded those previously reported to exert taste effects. We conclude that any effect of plasma leptin on taste responsiveness to sweeteners is subtle and manifests itself only under specific experimental conditions. PMID:25740302

  20. [The diversity of leptin].

    PubMed

    Mai, Knut

    2015-12-01

    The role of leptin in regulation of energy homeostasis is well established, yet both the diagnostic as well as the therapeutic relevance of leptin in diet-induced obesity remains unresolved. Nevertheless, in the last few years, the substantial impact of leptin substitution in selected forms of monogenic obesity has advanced our knowledge about the neuroendocrine network of body weight regulation. Moreover, leptin seems to play a crucial role in intestinal nutrient reabsorption, regulation of blood pressure, fertility, inflammation and autoimmune diseases. A better understanding of these processes could possibly provide novel diagnostic and therapeutic options in the future. PMID:26625227

  1. Role of C Reactive Protein (CRP) in Leptin Resistance

    PubMed Central

    Hribal, Marta Letizia; Fiorentino, Teresa Vanessa; Sesti, Giorgio

    2014-01-01

    Increased plasma levels of both leptin and C reactive protein (CRP) have been reported in a number of conditions, including obesity, and have been linked to cardiovascular pathophysiological processes and increased cardiovascular risk; interestingly these two biomarkers appear to be able to reciprocally regulate their bioavailability, through complex mechanisms that have not been completely clarified yet. Here we first review clinical evidence suggesting not only that the circulatory levels of CRP and leptin show an independent correlation, but also that assessing them in tandem may result in an increased ability to predict cardiovascular disease. We summarize also molecular studies showing that leptin is able to promote CRP production from hepatocytes and endothelial cells in vitro and discuss the studies addressing the possibility that in vivo leptin administration may be able to modulate plasma CRP levels. Furthermore, we describe two studies demonstrating that CRP directly binds leptin in extra-cellular settings, thus impairing its biological actions. Finally we report genetic evidence that common variations at the leptin receptor locus are associated with CRP blood levels. Overall, the data reviewed here show that the chronic elevation of CRP observed in obese subjects may worsen leptin resistance, contributing to the pathogenesis of cardiovascular disease, and highlight a potential link between conditions, such as leptin resistance and endothelial dysfunction, that may be amenable of pharmacological treatment targeted to the disruption of leptin-CRP interaction. PMID:23688010

  2. The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression.

    PubMed

    Aubert, Grégory; Mansuy, Virginie; Voirol, Marie-Jeanne; Pellerin, Luc; Pralong, François P

    2011-03-01

    Metformin demonstrates anorectic effects in vivo and inhibits neuropeptide Y expression in cultured hypothalamic neurons. Here we investigated the mechanisms implicated in the modulation of feeding by metformin in animals rendered obese by long-term high-fat diet (diet-induced obesity [DIO]) and in animals resistant to obesity (diet resistant [DR]). Male Long-Evans rats were kept on normal chow feeding (controls) or on high-fat diet (DIO, DR) for 6 months. Afterward, rats were treated 14 days with metformin (75 mg/kg) or isotonic sodium chloride solution and killed. Energy efficiency, metabolic parameters, and gene expression were analyzed at the end of the high-fat diet period and after 14 days of metformin treatment. At the end of the high-fat diet period, despite higher leptin levels, DIO rats had higher levels of hypothalamic neuropeptide Y expression than DR or control rats, suggesting a central leptin resistance. In DIO but also in DR rats, metformin treatment induced significant reductions of food intake accompanied by decreases in body weight. Interestingly, the weight loss achieved by metformin was correlated with pretreatment plasma leptin levels. This effect was paralleled by a stimulation of the expression of the leptin receptor gene (ObRb) in the arcuate nucleus. These data identify the hypothalamic ObRb as a gene modulated after metformin treatment and suggest that the anorectic effects of the drug are potentially mediated via an increase in the central sensitivity to leptin. Thus, they provide a rationale for novel therapeutic approaches associating leptin and metformin in the treatment of obesity. PMID:20303124

  3. Outcomes from Higher-Level Vocational Education and Training Qualifications

    ERIC Educational Resources Information Center

    Stanwick, John

    2006-01-01

    Where do higher-level vocational education and training (VET) qualifications lead? This study investigates whether they lead to employment at associate professional or higher occupations, or whether they are a pathway to university studies. Findings indicate that there are good employment outcomes for some graduates, although often at below…

  4. Endurance training increases leptin expression in the retroperitoneal adipose tissue of rats fed with a high-sugar diet.

    PubMed

    de Queiroz, Karina Barbosa; Guimarães, Juliana Bohnen; Coimbra, Cândido Celso; Rodovalho, Gisele Vieira; Carneiro, Cláudia Martins; Evangelista, Elísio Alberto; Guerra-Sá, Renata

    2014-01-01

    The presence of leptin receptors in white adipose tissue (WAT) suggests a type of peripheral control during the development of obesity and other metabolic disorders. Both diet composition and exercise influence serum leptin; however, the effect of their combination on long-term WAT leptin metabolism is unknown. In this study, rats fed with standard or high-sugar diets (HSD) were simultaneously subjected to running training for 4- and 8-week periods, and the retroperitoneal WAT (rWAT) was evaluated for adipocyte cell size, lipid and catecholamine content, Lep, OB-Rb and Ucp2 mRNA transcription levels, and circulating leptin and non-esterified fatty acids (NEFA). The HSD groups displayed a higher adiposity index and rWAT weight, Lep mRNA and protein upregulation, and a period-dependent effect on OB-Rb mRNA expression. Exercise decreased serum leptin and upregulated the OB-Rb mRNA levels. However, in rats fed with an HSD, the increase in OB-Rb mRNA and reduction in catecholamine levels resulted in a high level of adiposity and hyperleptinemia. The combination of training and an HSD decreases the NEFA levels and upregulating the Ucp2 mRNA expression in the 4-week period, while downregulating the Ucp2 mRNA expression in the 8-week period without changing the NEFA levels. Our results suggest that an HSD induces an increase in leptin expression in rWAT, while reducing adipocytes via leptin-mediated lipolysis after an 8-week period. In exercised rats fed an HSD, TAG synthesis and storage overlaps with lipolysis, promoting fat store development and Lep mRNA and plasma protein upregulation in adult rats. PMID:24243000

  5. Biologically inactive leptin and early-onset extreme obesity.

    PubMed

    Wabitsch, Martin; Funcke, Jan-Bernd; Lennerz, Belinda; Kuhnle-Krahl, Ursula; Lahr, Georgia; Debatin, Klaus-Michael; Vatter, Petra; Gierschik, Peter; Moepps, Barbara; Fischer-Posovszky, Pamela

    2015-01-01

    Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss. PMID:25551525

  6. Interactive Learning in a Higher Education Level 1 Mechanics Module.

    ERIC Educational Resources Information Center

    Booth, Kathryn M.; James, Brian W.

    2001-01-01

    Encourages Level 1 students (those taking a subject for the first time at the higher education level) to develop a deeper learning approach. Uses a cooperative learning approach to pose conceptual questions for interactive discussions and changes both teaching method and form of examination paper for a Mechanics module. (Contains 17 references.)…

  7. Effects of cereal fiber on leptin resistance and sensitivity in C57BL/6J mice fed a high-fat/cholesterol diet

    PubMed Central

    Zhang, Ru; Jiao, Jun; Zhang, Wei; Zhang, Zheng; Zhang, Weiguo; Qin, Li-Qiang; Han, Shu-Fen

    2016-01-01

    Background Cereal fiber is reported to be associated with obesity and metabolic diseases. However, whether cereal fiber improves leptin resistance and sensitivity remains unclear. Design For 24 weeks, 48 male C57BL/6J mice were randomly given a normal chow diet (Chow), high-fat/cholesterol diet (HFD), HFD with 0.8% oat fiber (H-oat) or HFD with 0.8% wheat bran fiber (H-wheat). At the end of feeding period, both the serum insulin and leptin levels were determined by ELISA kits. Western blotting was used to assess the protein expressions of the leptin receptor (LepR) and the leptin-signaling pathway in the adipose tissues. Results Our results suggested that mice fed oat or wheat bran fiber exhibited lower body weight, serum lipids, as well as insulin and leptin levels. The two cereal fibers potently increased the protein expressions of LepR in the adipose tissue. In addition, protein expressions of Janus kinase 2 (JAK2) and transcription 3 (STAT3) (induced by LepR), which enhances leptin signaling, were significantly higher and the expression of cytokine signaling-3 (SOCS3), which inhibits leptin signaling, was significantly lower in the two cereal fiber groups than in the HFD group. Conclusion Taken together, our findings suggest that cereal fiber can improve leptin resistance and sensitivity by the JAK2/STAT3 pathway in C57BL/6J mice fed a HFD; furthermore, oat fiber is more effective in the improvement of leptin sensitivity than wheat bran fiber, in this murine model. PMID:27534844

  8. Dysregulation of Glucose Homeostasis Following Chronic Exogenous Administration of Leptin in Healthy Sprague-Dawley Rats

    PubMed Central

    Wjidan, Khalil; Ibrahim, Effendi; Caszo, Brinnell; Gnanou, Justin

    2015-01-01

    Introduction Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. Aim To examine the effects of chronic leptin administration on plasma glucose regulation in rats. Materials and Methods Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. Results Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. Conclusion Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats. PMID:26816939

  9. Lean heart: Role of leptin in cardiac hypertrophy and metabolism

    PubMed Central

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-01-01

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  10. Peritoneal clearance of leptin in continuous ambulatory peritoneal dialysis.

    PubMed

    Arkouche, W; Juillard, L; Delawari, E; Lasne, Y; Combarnous, F; Sibaï-Galland, R; Traeger, J; Laville, M; Fouque, D

    1999-11-01

    Leptin is a 16-kd protein that increases energy expenditure and limits food intake. Serum leptin (S-leptin) is elevated in dialysis patients, and little data have been reported on leptin clearance (Cl) during dialysis. We analyzed the peritoneal dialysis (PD) Cl of leptin in 15 continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results to beta(2)-microglobulin (beta(2)-m), urea, and creatinine PD Cl. S-leptin was significantly elevated (Kruskal-Wallis, P < 0.005) in CAPD women (58.4 +/- 42.4 [SE] microg/L, n = 5) as compared with CAPD men (13.9 +/- 7.1, n = 10) and with healthy women (11.0 +/- 1.4, n = 13) and men (5.1 +/- 0. 9, n = 14). Correlations were found between percent of fat mass and S-leptin (P < 0.05); between S-leptin and the 24-hour PD leptin (P < 0.05); and between dialysate-to-plasma (D/P) beta(2)-m and D/P leptin (P < 0.01). PD leptin Cl (1.80 +/- 0.43 mL/min/1.73 m(2)) was higher than beta(2)-m Cl (1.22 +/- 0.31) (P < 0.01), but reduced as compared with urea Cl (8.84 +/- 1.20) (P < 0.005) and creatinine Cl (7.71 +/- 0.99) (P < 0.005). These results indicate that leptin is eliminated through the peritoneum membrane. However, peritoneal leptin clearance, as beta(2)-m, appears to be clearly restricted as compared with peritoneal transport of smaller molecules. Hence, leptin could use the same diffusion transport pathway as beta(2)-m. In addition, leptin, which has a higher molecular weight than beta(2)-m, was significantly more eliminated into the peritoneal dialysate. More studies are necessary to clarify whether this is an active leptin elimination process by peritoneal secretion or by a different restriction coefficient of diffusion through the peritoneum membrane. PMID:10561139

  11. Presenting Twins Are Exposed to Higher Levels of Inflammatory Mediators than Nonpresenting Twins as Early as the Midtrimester of Pregnancy

    PubMed Central

    Lee, Seung Mi; Park, Joong Shin; Norwitz, Errol R.; Kim, Sun Min; Lee, JoonHo; Park, Chan-Wook; Kim, Byoung Jae; Jun, Jong Kwan

    2015-01-01

    Objective Presenting twins are less likely to develop respiratory complications than non-presenting twins. The precise reason for this difference is not well understood, although it is known that the presence of inflammation reduces the risk of respiratory morbidity at birth. To further investigate this association, we compared the concentrations of inflammatory biomarkers in mid-trimester amniotic fluid (AF) of asymptomatic twin pairs. Study Design The study population consisted of women with twin pregnancies who underwent mid-trimester amniocentesis (15–20 weeks) for routine clinical indications and delivered at term. AF was analyzed for pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-15, IFN-γ, TNF-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-12), and chemokines (Complement Factor D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, CRP, CCL2/MCP-1, Leptin, Resistin) using Luminex Performance Assay multiplex kits. Data were analyzed using Wilcoxon signed rank test. Results A total of 82 twin pairs were enrolled. Mid-trimester AF concentrations of IL-8, MMP-8, CRP, MCP-1, leptin, and resistin were significantly higher in the presenting twin compared with the non-presenting twin (p<0.05 for each). Differences in AF concentrations of IL-8, MMP-8, and CRP persisted after adjustment for the fetal growth restriction at the time of birth and chorionicity. Conclusion These data suggest that, as early as the mid-trimester, the presenting fetus in an otherwise uncomplicated twin pregnancy is exposed to higher levels of pro-inflammatory mediators (especially IL-8, MMP-8, and CRP) than its non-presenting co-twin. Whether this pro-inflammatory milieu reduces the risk of neonatal respiratory morbidity at birth or has other functional implications needs to be further evaluated. PMID:26076029

  12. Resistin, Visfatin, Adiponectin, and Leptin: Risk of Breast Cancer in Pre- and Postmenopausal Saudi Females and Their Possible Diagnostic and Predictive Implications as Novel Biomarkers

    PubMed Central

    Assiri, Adel M. A.; Kamel, Hala F. M.; Hassanien, Mohamed F. R.

    2015-01-01

    The mechanisms of obesity-induced breast carcinogenesis are not clear. One hypothesis is that high levels of adipokines could promote breast cancer (BC) development. The aim of this study was to investigate the correlation of resistin, visfatin, adiponectin, and leptin with BC risk in pre- and postmenopausal females. A total of 82 BC newly diagnosed and histologically confirmed patients and 68 age and BMI matched healthy controls were enrolled. Both groups were subdivided into post- and premenopausal subgroups. Resistin, visfatin, adiponectin, and leptin were measured by ELISA. There were significantly higher levels of leptin, resistin, and visfatin in postmenopausal BC patients than their respective controls. Only in postmenopausal subgroups, leptin, resistin, and visfatin levels were positively correlated with TNM staging, tumor size, lymph node (LN) metastasis, and histological grading. In postmenopausal females, multivariate logistic regression analysis revealed that adiponectin, leptin, visfatin, and resistin were risk factors for BC. Our results suggested that serum resistin, leptin, adiponectin, and visfatin levels as risk factors for postmenopausal BC may provide a potential link with clinicopathological features and are promising to be novel biomarkers for postmenopausal BC. PMID:25838618

  13. Leptin and reproductive function.

    PubMed

    Hausman, Gary J; Barb, C Richard; Lents, Clay A

    2012-10-01

    Adipose tissue plays a dynamic role in whole-body energy homeostasis by acting as an endocrine organ. Collective evidence indicates a strong link between neural influences and adipocyte expression and secretion of leptin. Developmental changes in these relationships are considered important for pubertal transition in reproductive function. Leptin augments secretion of gonadotropin hormones, which are essential for initiation and maintenance of normal reproductive function, by acting centrally at the hypothalamus to regulate gonadotropin-releasing hormone (GnRH) neuronal activity and secretion. The effects of leptin on GnRH are mediated through interneuronal pathways involving neuropeptide-Y, proopiomelanocortin and kisspeptin. Increased infertility associated with diet induced obesity or central leptin resistance are likely mediated through the kisspeptin-GnRH pathway. Furthermore, Leptin regulates reproductive function by altering the sensitivity of the pituitary gland to GnRH and acting at the ovary to regulate follicular and luteal steroidogenesis. Thus leptin serves as a putative signal that links metabolic status with the reproductive axis. The intent of this review is to examine the biological role of leptin with energy metabolism, and reproduction. PMID:22980196

  14. Postnatal Leptin Promotes Organ Maturation and Development in IUGR Piglets

    PubMed Central

    Attig, Linda; Brisard, Daphné; Larcher, Thibaut; Mickiewicz, Michal; Guilloteau, Paul; Boukthir, Samir; Niamba, Claude-Narcisse; Gertler, Arieh; Djiane, Jean; Monniaux, Danielle; Abdennebi-Najar, Latifa

    2013-01-01

    Babies with intra-uterine growth restriction (IUGR) are at increased risk for experiencing negative neonatal outcomes due to their general developmental delay. The present study aimed to investigate the effects of a short postnatal leptin supply on the growth, structure, and functionality of several organs at weaning. IUGR piglets were injected from day 0 to day 5 with either 0.5 mg/kg/d leptin (IUGRLep) or saline (IUGRSal) and euthanized at day 21. Their organs were collected, weighed, and sampled for histological, biochemical, and immunohistochemical analyses. Leptin induced an increase in body weight and the relative weights of the liver, spleen, pancreas, kidneys, and small intestine without any changes in triglycerides, glucose and cholesterol levels. Notable structural and functional changes occurred in the ovaries, pancreas, and secondary lymphoid organs. The ovaries of IUGRLep piglets contained less oogonia but more oocytes enclosed in primordial and growing follicles than the ovaries of IUGRSal piglets, and FOXO3A staining grade was higher in the germ cells of IUGRLep piglets. Within the exocrine parenchyma of the pancreas, IUGRLep piglets presented a high rate of apoptotic cells associated with a higher trypsin activity. In the spleen and the Peyer’s patches, B lymphocyte follicles were much larger in IUGRLep piglets than in IUGRSal piglets. Moreover, IUGRLep piglets showed numerous CD79+cells in well-differentiated follicle structures, suggesting a more mature immune system. This study highlights a new role for leptin in general developmental processes and may provide new insight into IUGR pathology. PMID:23741353

  15. Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats.

    PubMed

    Scarpace, P J; Matheny, M; Zhang, Y; Tümer, N; Frase, C D; Shek, E W; Hong, B; Prima, V; Zolotukhin, S

    2002-03-01

    The purpose of this study was to determine if long-term leptin treatment desensitizes leptin signal transduction and the subsequent downstream anorexic and thermogenic responses in normal and leptin-resistant age-related obese rats. To this end, we administered, i.c.v., recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or control virus into young and aged-obese rats and after 9 or 46 days, examined food intake, oxygen consumption, body weight, serum leptin, STAT3 phosphorylation, hypothalamic NPY and POMC mRNAs, and UCP1 expression and protein level in brown adipose tissue (BAT). In young rats, rAAV-leptin depleted body fat and both anorexic and thermogenic mechanisms contributed to this effect. Moreover, leptin signal transduction was not desensitized, and there were persistent physiological responses. Similarly, in the aged-obese rats, there was unabated leptin signal transduction, however, both the anorexic and thermogenic responses completely attenuated sometime after day 9. This attenuation, downstream of the leptin receptor, may be contributing to the leptin-resistance and age-related weight gain in these aged-obese rats. Finally, in young rats, although the initial responses to rAAV-leptin were dominated by anorexic responses, by 46 days, the predominant response was thermogenic rather than anorexic, suggesting that energy expenditure may be an important component of long-term weight maintenance. PMID:11955525

  16. Leptin as a potential treatment for obesity: progress to date.

    PubMed

    Bell-Anderson, Kim S; Bryson, Janet M

    2004-01-01

    Despite significant reductions in the consumption of dietary fat, the prevalence of obesity is steadily rising in western civilization. Of particular concern is the recent epidemic of childhood obesity, which is expected to increase the incidence of obesity-related disorders. The obese gene (ob) protein product leptin is a hormone that is secreted from adipocytes and functions to suppress appetite and increase energy expenditure. Leptin is an attractive candidate for the treatment of obesity as it is an endogenous protein and has been demonstrated to have potent effects on bodyweight and adiposity in rodents. Whereas leptin has been successfully used in the treatment of leptin-deficient obese patients, trials in hyperleptinemic obese patients have yielded variable results. Long-acting leptins have been tried but with no greater success. Other strategies including the use of leptin analogs and other factors that bypass normal leptin delivery systems are being developed. Identifying the mechanisms at the molecular level by which leptin functions will create new avenues for pharmaceutical targeting to simulate the intracellular effects of leptin. PMID:15743109

  17. Diabetes insipidus and increased serum levels of leptin and lactate-dehydrogenase (LDH) in an adolescent boy with a primary intracranial germinoma. Case report and an endocrinological revaluation of literature.

    PubMed

    Carella, C; Rotondi, M; Del Buono, A; Sinisi, A M; Del Basso De Caro, M L; Mone, C M; Vizioli, L; Sorvillo, F; Mazziotti, G; Bellastella, A

    1999-01-01

    A 16-year-old boy presented with a four-month history of polyuria-polydipsia and a diplopia which had reverted after treatment. The neuroimaging studies performed had been strongly suggestive of an optic nerve glioma, while endocrinological investigation (beta-hCG 420 IU/L) has lead to the correct diagnosis later confirmed at the immunohystochemical analysis performed at biopsy. The high serum level of hCG was unaffected by bromocriptine nor octreotide, while the PRL level (80.0 microg/L) was reduced only by bromocriptine. Among the several tumor markers which may be secreted by such lesions, ours is the first reported case of an elevation of serum LDH for a primary intracranial germinoma. Moreover, the elevated value of serum leptin reported by us might be due to the insensitivity of the hypothalamic structures to endogenous leptin. PMID:10475155

  18. Chemical identity of hypothalamic neurons engaged by leptin in reproductive control.

    PubMed

    Ratra, Dhirender V; Elias, Carol F

    2014-11-01

    The adipocyte-derived hormone leptin plays a critical role as a metabolic cue for the reproductive system. Conditions of low leptin levels observed in negative energy balance and loss-of-function mutations of leptin or leptin receptor genes are characterized by decreased fertility. In recent years, advances have been made for identifying possible hypothalamic neurons relaying leptin's neuroendocrine control of reproductive function. Studies from different laboratories have demonstrated that leptin action in the hypothalamo-pituitary-gonadal (HPG) axis is exerted via hypothalamic interneurons regulating gonadotropin-releasing hormone (GnRH) cells, oppose to direct action on GnRH neurons. Following this observation, studies focused on identifying leptin responsive interneurons. Using a Cre-loxP system to re-express or delete the leptin receptor long form (LepRb) from kisspeptin neurons, our laboratory found that leptin's action on kiss1 cells is neither required nor sufficient for leptin's role in reproductive function. Endogenous re-expression of LepRb however, in glutamatergic neurons of the ventral premammilary nucleus (PMV) or ablation of agouti-related protein (AgRP) neurons from leptin signaling-deficient mice are both sufficient to induce puberty and improve fertility. Recent studies have also shown that leptin action in first order GABAergic neurons is required for fertility. Together, these studies begin to delineate key neuronal populations involved in leptin's action in reproduction. In this review, we discuss recent advances made in the field and highlight the questions yet to be answered. PMID:24915437

  19. Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus

    PubMed Central

    Iwakura, Hiroshi; Dote, Katsuko; Bando, Mika; Koyama, Hiroyuki; Hosoda, Kiminori; Kangawa, Kenji; Nakao, Kazuwa

    2016-01-01

    Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus—derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A—positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability. PMID:26849804

  20. Leptin's Role in Lipodystrophic and Nonlipodystrophic Insulin-Resistant and Diabetic Individuals

    PubMed Central

    Moon, Hyun-Seuk; Dalamaga, Maria; Kim, Sang-Yong; Polyzos, Stergios A.; Hamnvik, Ole-Petter; Magkos, Faidon; Paruthi, Jason

    2013-01-01

    Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes. PMID:23475416

  1. Teaching Higher Level Thinking Skills through Computer Courseware.

    ERIC Educational Resources Information Center

    Edwards, Lois

    A rationale is presented for teaching gifted students to gain computer literacy, learn programing, use utility software (e.g., word processing packages), and use interactive educational courseware containing drills, simulations, or educational strategy games to develop higher level and creative thinking skills. Evaluation of courseware for gifted…

  2. Middle Level Technician/Higher Technical & Business Skills. Evaluation Report.

    ERIC Educational Resources Information Center

    European Social Fund, Dublin (Ireland).

    A study examined European Social Fund (ESF)-funded middle-level technician (MLT) and higher technical and business skills (HTBS) courses at Irish technical colleges. Data were obtained from the following: review of relevant literature; review of all program-monitoring documents submitted by Ireland's Department of Education since 1990; interviews…

  3. Seeking a Higher Level of Arts Integration across the Curriculum

    ERIC Educational Resources Information Center

    Sotiropoulou-Zormpala, Marina

    2016-01-01

    To seek a higher level of arts integration across the education curriculum, I investigated designs of teaching through arts activities that would motivate educators to adopt the spirit of "aesthetic teaching." Two different designs were tested, with the second as a continuation of the first. Each ascribes a different educational role to…

  4. Leptin reduces hyperactivity in an animal model for anorexia nervosa via the ventral tegmental area.

    PubMed

    Verhagen, Linda A W; Luijendijk, Mieneke C M; Adan, Roger A H

    2011-03-01

    Hyperactivity in anorexia nervosa (AN) is associated with low plasma leptin levels and negatively impacts on disease outcome. Using an animal model that mimics features of AN including food-restriction induced hyperlocomotion, we demonstrate that central leptin injections in the lateral ventricle and local injections of leptin into the ventral tegmental area (VTA) suppress running wheel activity. The results support that falling levels of leptin, that accompany caloric restriction, result in increased activity levels because of decreased leptin signaling in the VTA, part of the mesolimbic reward system. PMID:21190812

  5. The Regulation of Leptin, Leptin Receptor and Pro-opiomelanocortin Expression by N-3 PUFAs in Diet-Induced Obese Mice Is Not Related to the Methylation of Their Promoters

    PubMed Central

    2011-01-01

    Background The expression of leptin is increased in obesity and inhibited by n-3 polyunsaturated fatty acids (n-3 PUFAs), but the underlying molecular mechanisms have not been firmly established. Methods In this study, we investigated the effects of dietary n-3 PUFAs on the methylation of CpG islands in the promoter regions of the leptin, leptin-R and POMC genes, as well as the effects of n-3 PUFA status in early life on the modification of the promoters of these three genes. Male C57 BL/6J mice were fed a high-fat diet with one of four different fat types: sunflower oil (n-3 PUFA deficient), soy oil, fish oil, or a mixture of soy and fish oil (soy:fish oil = 1:1). Two low-fat diets with sunflower oil or soy oil served as controls. Female mice were fed two breeding diets, sunflower oil or a mixture of soy and fish oil (soy:fish oil = 1:1), during pregnancy and lactation to breed new pups. Results Compared to mice fed the control diets, the expression of leptin in fat tissue and leptin-R and POMC in the hypothalamus was higher in the diet-induced obesity (DIO) mice, and the n-3 PUFAs in the diets reversed these elevated expression levels. The mean methylation levels of CpG sites in the promoter regions of the leptin and POMC genes showed no difference between the DIO and the control diet groups nor between the n-3 PUFA-containing and -deficient diet groups. For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups. Feeding mice with the n-3 PUFA diet during pregnancy and lactation did not affect CpG methylation in the leptin or POMC promoters. Conclusions Our findings indicate that promoter DNA methylation may not be related to the expression of leptin, leptin-R or its related hypothalamic satiety regulator POMC. PMID:21609458

  6. The Role of State Higher Education Governance Structures in State-Level Higher Education Lobbying

    ERIC Educational Resources Information Center

    Burkum, Kurt Richard

    2009-01-01

    Lobbying and lobbyists are integral components of federal and state public policymaking for higher education at the federal and state levels. While the actions and goals of lobbyists appear to be straightforward, the lobbying tactics selected by lobbyists vary for different situations and in different contexts (Browne, 1985; Cook, 1998; Gladieux &…

  7. Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence.

    PubMed

    Kratzsch, J; Lammert, A; Bottner, A; Seidel, B; Mueller, G; Thiery, J; Hebebrand, J; Kiess, W

    2002-10-01

    Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation. PMID:12364439

  8. Transcriptional Characterization of Porcine Leptin and Leptin Receptor Genes.

    PubMed

    Pérez-Montarelo, Dafne; Fernández, Almudena; Barragán, Carmen; Noguera, Jose L; Folch, Josep M; Rodríguez, M Carmen; Ovilo, Cristina; Silió, Luis; Fernández, Ana I

    2013-01-01

    The leptin (LEP) and its receptor (LEPR) regulate food intake and energy balance through hypothalamic signaling. However, the LEP-LEPR axis seems to be more complex and its expression regulation has not been well described. In pigs, LEP and LEPR genes have been widely studied due to their relevance. Previous studies reported significant effects of SNPs located in both genes on growth and fatness traits. The aim of this study was to determine the expression profiles of LEP and LEPR across hypothalamic, adipose, hepatic and muscle tissues in Iberian x Landrace backcrossed pigs and to analyze the effects of gene variants on transcript abundance. To our knowledge, non porcine LEPR isoforms have been described rather than LEPRb. A short porcine LEPR isoform (LEPRa), that encodes a protein lacking the intracellular residues responsible of signal transduction, has been identified for the first time. The LEPRb isoform was only quantifiable in hypothalamus while LEPRa appeared widely expressed across tissues, but at higher levels in liver, suggesting that both isoforms would develop different roles. The unique LEP transcript showed expression in backfat and muscle. The effects of gene variants on transcript expression revealed interesting results. The LEPRc.1987C>T polymorphism showed opposite effects on LEPRb and LEPRa hypothalamic expression. In addition, one out of the 16 polymorphisms identified in the LEPR promoter region revealed high differential expression in hepatic LEPRa. These results suggest a LEPR isoform-specific regulation at tissue level. Conversely, non-differential expression of LEP conditional on the analyzed polymorphisms could be detected, indicating that its regulation is likely affected by other mechanisms rather than gene sequence variants. The present study has allowed a transcriptional characterization of LEP and LEPR isoforms on a range of tissues. Their expression patterns seem to indicate that both molecules develop peripheral roles apart from

  9. [Serum leptin in women during the third trimester of pregnancy].

    PubMed

    Stejskal, D; Růzicka, V; Novák, J; Jedelský, L; Bartek, J; Horalík, D

    1998-10-01

    Leptin is a small protein produced mainly by adipocytes. Recently, its relationship to obesity has been studied extensively. It was proved that obese individuals have either relative or absolute leptin deficiency. Several years ago, leptin was found to be produced also by the placenta. This stimulated us to study relationship between leptinemia and placental hormones in 85 women in the second gravidity trimester. Within the prenatal screening, these pregnant women were subjected to analysis of AFP, hCG, SP-1 glycoprotein and leptin and the results obtained were processed statistically. The control group consisted of 20 nonpregnant women with tetany. Women in the second gravidity trimester were found to have a significantly higher leptinemia than nongravid women (even with respect to body weight). This may be due to a larger amount of adipose tissue during gravidity and also leptin-resistance. Moreover, we recorded a negative correlation between leptinemia related to body weight and concentration of SP-1 glycoprotein. This finding supports the presumption that mother's leptinemia correlated negatively in the second gravidity trimester with quality and quantity of the placental syncytiotrophoblast. Our findings can be explained as follows: the biological effect of leptin is metabolically unfavourable for the growth of the foetus and the placenta. An increased leptinemia with advancing gravidity can be caused by a larger fatty mass and an increased activity of adipocytes when leptin presence increases in system circulation but the organism begins to be leptin-resistant and an "unfavourable" metabolic effect fort the gravid woman and the foetus is not distinct. These findings thus support the hypothesis postulating the nonsignificance of leptin production in human placenta and on the contrary the necessity of leptin-resistance for foetus development from the metabolic point of view. Thus, a decreased leptinemia immediately before and after the delivery could be caused

  10. Long-Lived αMUPA Mice Show Attenuation of Cardiac Aging and Leptin-Dependent Cardioprotection

    PubMed Central

    Levy, Esther; Kornowski, Ran; Gavrieli, Reut; Fratty, Ilana; Greenberg, Gabriel; Waldman, Maayan; Birk, Einat; Shainberg, Asher; Akirov, Amit; Miskin, Ruth; Hochhauser, Edith

    2015-01-01

    αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR. PMID:26673217