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Sample records for apob lpl leptin

  1. Genetic association study of selected candidate genes (ApoB, LPL, Leptin and telomere length in obese and hypertensive individuals

    Directory of Open Access Journals (Sweden)

    Saini Divyalakshmi

    2009-09-01

    Full Text Available Abstract Background A genetic study was carried out among obese and hypertensive individuals from India to assess allelic association, if any, at three candidate loci: Apolipoprotein B (ApoB minisatellite and two tetranucleotide repeat loci; LPL (Lipoprotein lipase and Leptin. Attempt has also been made to find out whether telomere length attrition is associated with hypertension and obese individuals. Methods Venous blood samples were collected from 37 normal, 35 obese and 47 hypertensive individuals. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMC and PCR amplifications were achieved using locus specific primers. Genotyping of ApoB minisatellite was performed using 4% polyacrylamide gel electrophoresis (PAGE followed by silver staining, whereas LPL and Leptin loci were genotyped using ALF Express™ DNA sequencer. Telomere length was determined using a recently developed real time based quantitative PCR, where the relative telomere length was determined by calculating the relative ratio of telomere (T and single copy gene (S PCR products which is expressed as T/S ratio. Results All the three loci are highly polymorphic, display high heterozygosity and conform to Hardy-Weinberg's equilibrium expectations. ApoB minisatellite displayed 14 alleles, whereas LPL and Leptin tetranucleotide loci were having 9 and 17 alleles, respectively. Interestingly two new alleles (9 and 11 repeats were detected at ApoB locus for the first time. The alleles at Leptin locus were classified as Class I (lower alleles: 149-200 bp and Class II alleles (higher alleles: >217 bp. Higher alleles at ApoB (>39 repeats, predominant allele 9 at LPL and alleles 164 bp and 224 bp at Leptin loci have shown allelic association with hypertensive individuals. After adjusting the influence of age and gender, the analysis of co-variance (ANCOVA revealed the relative telomere length (T/S ratio in hypertensive individuals to be (1.01 ± 0.021, which was

  2. [Leptin].

    Science.gov (United States)

    Nedvídková, J

    1997-12-01

    Leptin (ob-protein), a previously unknown protein signal, is secreted from adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks, that regulate weight and energy homeostasis. Leptin provides a communication link between fat tissue and the brain. Ob protein appears to play a major role in the control of body fat stores through coordinated regulation of feeding behavior, metabolism, autonomic nervous system and body energy balance in rodents, primates and humans. Leptin levels have pulsative and diurnal character. In lean subjects with relatively low adipose tissue, the majority of circulating leptin is in the bound form. On other hand, in obese individuals the majority of leptin circulates in free form presumably bioactive protein, and thus obese subjects are resistant to free leptin. Leptin's resistance is often coupled with insuline resistance postreceptor type. Leptin receptor is product of db genes. Ob-protein receptor belongs to the cytokine superfamily of receptors and has several variants. Leptin-receptor gene is expressed in abundant degree in ovary, uterus, testes, less in hypothalamus, hypophysis, and little in kidney. Leptin stimulates the reproductive endocrine system and may serve as a permissive signal to the reproductive system of normal animals. Ob-gene product, leptin is regulated by feedings patterns and hormones, such as insulin and glucocorticoids. There is assumed that neuropeptide Y (NPY) and melanocyte-stimulating hormone (MSH) and its receptor (MCR) are a critical components of the biological response to leptin levels. MCR in contrast to leptin receptors are coupled with G-transduction system.

  3. Calculation of LDL apoB

    NARCIS (Netherlands)

    Sniderman, A.D.; Tremblay, A.J.; Graaf, J. de; Couture, P.

    2014-01-01

    OBJECTIVES: This study tests the validity of the Hattori formula to calculate LDL apoB based on plasma lipids and total apoB. METHODS: In 2178 patients in a tertiary care lipid clinic, LDL apoB calculated as suggested by Hattori et al. was compared to directly measured LDL apoB isolated by

  4. Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency

    DEFF Research Database (Denmark)

    Rodrigues, Rute; Artieda, Marta; Tejedor, Diego

    2016-01-01

    BACKGROUND: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight...... into the deleterious effect of the mutations is clinically essential. METHODS: We used gene sequencing followed by in-vivo/in-vitro and in-silico tools for classification. We classified 125 rare LPL mutations in 33 subjects thought to have LPL deficiency and in 314 subjects selected for very SHTG. RESULTS: Of the 33...

  5. Mobility of “HSPG-bound” LPL explains how LPL is able to reach GPIHBP1 on capillaries

    DEFF Research Database (Denmark)

    Allan, Christopher M; Larsson, Mikael; Jung, Rachel S

    2017-01-01

    , thereby preventing LPL from reaching GPIHBP1 on capillaries. We hypothesized that LPL-HSPG interactions are transient, allowing the LPL to detach and move to GPIHBP1 on capillaries. Indeed, we found that LPL detaches from HSPGs on cultured cells and moves to: (1) soluble GPIHBP1 in the cell culture medium...

  6. Leptin increases skeletal muscle lipoprotein lipase and postprandial lipid metabolism in mice.

    Science.gov (United States)

    Donahoo, William T; Stob, Nicole R; Ammon, Stefen; Levin, Nancy; Eckel, Robert H

    2011-03-01

    The ability of leptin to preserve lean tissue during weight loss may be in part due to differences in nutrient partitioning. Because lipoprotein lipase (LPL) plays a key role in partitioning lipid nutrients, this study was conducted to test the hypothesis that leptin would modify the tissue-specific regulation of LPL and result in increased lipid oxidation and decreased storage. The effects of daily intraperitoneal leptin injections (2 mg/kg body weight) over 2 weeks on LPL activity and postprandial lipid metabolism were tested in both wild-type (WT), leptin-deficient ob/ob obese mice and mice pair fed to the leptin-treated mice. On the experimental day, mice were given food by gavage, blood was drawn periodically, and adipose tissue and skeletal muscle were harvested for measurements of LPL activity at 240 minutes. After 2 weeks of leptin administration, skeletal muscle LPL (SMLPL) activity was increased in leptin-treated compared with pair-fed (P = .012) and WT (P = .002) mice. There was no effect of leptin or pair feeding on postprandial adipose tissue LPL activity. In ob/ob mice, leptin treatment normalized the decrease in postprandial free fatty acid concentration (P = .066). Leptin had no effect on either the area under the triglyceride (TG) excursion or the integrated area under the TG excursion in WT mice. In ob/ob mice, however, the TG excursion was lower in the leptin-treated than the pair-fed mice by area under the TG excursion (P = .012) and was lower than in the WT mice by integrated area under the TG excursion (P = .027). As expected, 2 weeks of leptin treatment decreased body weight in both the WT and ob/ob mice (-2.6% and -10.4%, respectively). Leptin treatment increased SMLPL, an effect that may have contributed to the leptin-induced weight loss. The leptin-induced decreased postprandial TG excursion in ob/ob mice suggests that leptin acts to augment clearance of postprandial TG-rich lipoprotein lipid and that this increase may in part be secondary

  7. Effect of leptin level upon lipid metabolism in climacteric women

    International Nuclear Information System (INIS)

    Peng Lijing; Yan Ruming; Sun Enhua

    2005-01-01

    To observe the relationship between leptin and obesity of climacteric women with their lipid metabolism, 110 cases of climacteric women were chosen as observation group, consisting of 69 cases obese subgroup and 45 cases non-obese group, and 60 cases of normal reproduction- age women were arranged as control group. Blood levels of leptin, INS, LDL-C, TG, HDL-C, apoA1, apoB, LH, FSH, E-2, T, and P were detected and BMI was calculated. The results showed that blood levels of leptin and INS of obese subgroup were significantly higher than those of non-obese sub-group and control group(P<0.01), and that LDL-C(5.01 mmol/L), TG(2.21mmal/L) and apoB(0.89g/L) levels in obese subgroup were significantly higher than those of control group. Furthermore, an important observation was that in climacteric women group, blood leptin level was positively and significantly correlated with insulin, BMI and several atherogenic blood lipid parameters, including LDL-C, TG and apoB. Thus, a preliminary conclusion might be reached as that the high climacteric level of leptin is associated with abnormal lipid metabolism related to atherogenity, and so leptin and lipid metabolism as a whole should be paid more attention in climateric women, especially those with obesity. (authors)

  8. Polymorphism in APOB associated with increased low-density lipoprotein levels in both genders in the general population

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Jensen, Jan S

    2005-01-01

    Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial.......Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial....

  9. New mutations in APOB100 involved in familial hypobetalipoproteinemia

    DEFF Research Database (Denmark)

    Brusgaard, Klaus; Kjaersgaard, Lars; Hansen, Anne-Birthe Bo

    2011-01-01

    Familial hypolipoproteinemia (FHBL) is characterized by an inherited low plasma level of apolipoprotein B containing lipoproteins. FHBL may be caused by mutations of APOB. Individuals with FHBL typically have intestinal malabsorption and frequently suffer from a deficiency of fat-soluble vitamins....... Most mutations that cause FHBL are APOB truncating mutations. Here we describe a patient with FHBL caused by a novel truncating mutation together with a novel missense mutation....

  10. Evidence of a major locus for lipoprotein lipase (LPL) activity in addition to a pleiotropic locus for both LPL and fasting insulin: results from the HERITAGE Family Study.

    Science.gov (United States)

    Hong, Y; Rice, T; Després, J P; Gagnon, J; Nadeau, A; Bergeron, J; Pérusse, L; Bouchard, C; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C

    1999-06-01

    A major gene hypothesis for heparin releasable plasma lipoprotein lipase (PH-LPL) activity was assessed using segregation analyses of data on 495 members in 98 normolipidemic sedentary families of Caucasian descent who participated in the HERITAGE Family Study. Segregation analyses were performed on PH-LPL adjusted for age, and on PH-LPL activity adjusted for age and fasting insulin. Prior to adjustment for insulin, neither a major gene effect nor a multifactorial component could be rejected, and support for a major gene was equivocal i.e. neither the Mendelian transmission nor the no transmission (equal tau s) models were rejected. However, after adjusting for the effects of insulin, a major gene effect on PH-LPL activity was unambiguous. The putative locus accounted for 60% of the total phenotypic variance, and the homozygous recessive form affected 10% (q2) of the sample (i.e. gene frequency (q) = 0.31), and led to a low PH-LPL value. The lack of a significant multifactorial effect suggested that the familial etiology of PH-LPL activity adjusted for insulin was likely to be primarily a function of the major locus. In conclusion, the present study is the first to report segregation analyses on PH-LPL activity prior to and after adjusting for insulin, and suggests that there is an indication of a pleiotropic genetic effect on PH-LPL activity and insulin, in addition to a major gene effect on PH-LPL activity alone.

  11. Missense mutations in APOB within the betaalpha1 domain of human APOB-100 result in impaired secretion of ApoB and ApoB-containing lipoproteins in familial hypobetalipoproteinemia.

    Science.gov (United States)

    Burnett, John R; Zhong, Shumei; Jiang, Zhenghui G; Hooper, Amanda J; Fisher, Eric A; McLeod, Roger S; Zhao, Yang; Barrett, P Hugh R; Hegele, Robert A; van Bockxmeer, Frank M; Zhang, Hongyu; Vance, Dennis E; McKnight, C James; Yao, Zemin

    2007-08-17

    Familial hypobetalipoproteinemia (FHBL) is associated with mutations in the APOB gene. We reported the first missense APOB mutation, R463W, in an FHBL kindred (Burnett, J. R., Shan, J., Miskie, B. A., Whitfield, A. J., Yuan, J., Tran, K., Mc-Knight, C. J., Hegele, R. A., and Yao, Z. (2003) J. Biol. Chem. 278, 13442-13452). Here we identified a second nonsynonymous APOB mutation, L343V, in another FHBL kindred. Heterozygotes for L343V (n = 10) had a mean plasma apoB at 0.31 g/liter as compared with 0.80 g/liter in unaffected family members (n = 22). The L343V mutation impaired secretion of apoB-100 and very low density lipoproteins. The secretion efficiency was 20% for B100wt and 10% for B100LV and B100RW. Decreased secretion of mutant apoB-100 was associated with increased endoplasmic reticulum retention and increased binding to microsomal triglyceride transfer protein and BiP. Reduced secretion efficiency was also observed with B48LV and B17LV. Biochemical and biophysical analyses of apoB domain constructs showed that L343V and R463W altered folding of the alpha-helical domain within the N terminus of apoB. Thus, proper folding of the alpha-helical domain of apoB-100 is essential for efficient secretion.

  12. Inhibition of the apical sodium-dependent bile acid transporter reduces LDL cholesterol and apoB by enhanced plasma clearance of LDL apoB.

    Science.gov (United States)

    Huff, Murray W; Telford, Dawn E; Edwards, Jane Y; Burnett, John R; Barrett, P Hugh R; Rapp, Stephen R; Napawan, Nida; Keller, Bradley T

    2002-11-01

    Cloning of the ileal apical sodium-dependent bile acid transporter (ASBT) has identified a new pharmacological target for the modulation of plasma lipoproteins. The objective of this study was to determine whether a novel, specific, minimally absorbed ASBT inhibitor (SC-435) decreases LDL cholesterol through the alteration of plasma apoB kinetics. Miniature pigs were treated for 21 days with 10 mg/kg/day of SC-435 or placebo. SC-435 decreased plasma cholesterol by 9% and LDL cholesterol by 20% with no effect on other lipids. Autologous (131)I-VLDL, (125)I-LDL, and [(3)H]-leucine were injected simultaneously to determine apoB kinetics. LDL apoB concentrations decreased significantly by 10% resulting entirely from an increase in LDL-apoB fractional catabolic rate. SC-435 had no effect on either total LDL apoB production or VLDL apoB converted to LDL. SC-435 increased VLDL apoB production by 22%; however, the concentration was unchanged as a result of increased VLDL apoB direct removal. SC-435 increased hepatic mRNA and enzymatic activity for both cholesterol 7alpha-hydroxylase and HMG-CoA reductase. Hepatic LDL receptor mRNA increased significantly, whereas apoB expression was unaffected. A low dose of the ASBT inhibitor, SC-435, significantly reduces plasma LDL cholesterol through enhanced LDL receptor-mediated LDL apoB clearance, secondary to increased expression of cholesterol 7alpha-hydroxylase.

  13. A human apoB100 transgenic mouse expresses human apoB100 in the RPE and develops features of early AMD

    DEFF Research Database (Denmark)

    Fujihara, Masashi; Bartels, Emil; Nielsen, Lars B

    2009-01-01

    changes consistent with early human AMD including loss of basal infoldings and accumulation of cytoplasmic vacuoles in the RPE, and basal laminar deposits containing long-spacing collagen and heterogeneous debris in Bruch membrane of apoB100 mice. In apoB100 mice given a high-fat diet, basal linear...... transgenic for a human genomic fragment encoding the full length human apoB ("apoB100" mice) and litter-mate control mice were given a normal chow or high-fat diet for 12 months. Mice were evaluated for human apoB mRNA expression in the RPE/choroid and liver by RT-qPCR. Phenotypic changes associated......-like deposits were identified in 12-month-old mice. Linear regression analysis showed that the genotype (human apoB transgene) was a stronger influencing factor than high-fat diet in producing AMD-like lesions used in this study. Human apoB100 transgenic mice overexpress apoB in RPE and, with time, develop...

  14. The VLDL receptor plays a major role in chylomicron metabolism by enhancing LPL-mediated triglyceride hydrolysis

    NARCIS (Netherlands)

    Goudriaan, Jeltje R.; Espirito Santo, Sonia M. S.; Voshol, Peter J.; Teusink, Bas; van Dijk, Ko Willems; van Vlijmen, Bart J. M.; Romijn, Johannes A.; Havekes, Louis M.; Rensen, Patrick C. N.

    2004-01-01

    The VLDL receptor (VLDLr) is involved in tissue delivery of VLDL-triglyceride (TG)-derived FFA by facilitating the expression of lipoprotein lipase (LPL). However, vldlr-/- mice do not show altered plasma lipoprotein levels, despite reduced LPL expression. Because LPL activity is crucial in

  15. Lipoprotein metabolism in an apoB-80 familial hypobetalipoproteinemia heterozygote.

    Science.gov (United States)

    Hooper, Amanda J; Robertson, Ken; Champain, Danie; Hua, Jianmin; Song, Swithin; Parhofer, Klaus G; Barrett, P Hugh R; van Bockxmeer, Frank M; Burnett, John R

    2016-06-01

    Familial hypobetalipoproteinemia (FHBL) is characterized by mutations in APOB, the majority of these causing protein truncations, and low plasma levels of apolipoprotein (apo) B. The hypobetalipoproteinemia may be due to enhanced clearance and possibly reduced production of apoB-containing lipoproteins; the mechanism may depend on the length of the apoB truncation. We studied fasting lipoprotein metabolism in an FHBL subject heterozygous for a mutation causing a truncated apoB, apoB-80. Very low density lipoprotein (VLDL)-, intermediate density lipoprotein (IDL)-, and low density lipoprotein (LDL)-apoB kinetics were determined in the fasting state using stable isotope methods and compartmental modeling. Compared with lean normolipidemic controls the apoB-80 FHBL subject had an elevated VLDL-apoB fractional catabolic rate and lower LDL production. ApoB production rates and IDL- and LDL-apoB fractional catabolic rates were not different. FHBL subjects heterozygous for a mutation truncating apoB to 80% of full-length are able to produce VLDL-apoB normally, but have rapid clearance of these particles, resulting in low levels of circulating apoB. Copyright © 2016 The Canadian Society of Clinical Chemists. All rights reserved.

  16. Leptin and psychiatry

    African Journals Online (AJOL)

    QuickSilver

    obese and normal body weight controls, and negatively corre- lated with weight loss due to food restriction. Reports of studies of leptin in patients with anorexia nervosa are limited. In starved female anorectics at very low body weights, leptin levels are reduced significantly.15,16 Leptin in-. Fig. 2. A schematic representation ...

  17. LPL gene expression is associated with poor prognosis in CLL and closely related to NOTCH1 mutations

    DEFF Research Database (Denmark)

    Kristensen, Louise; Kielsgaard Kristensen, Thomas; Abildgaard, Niels

    2016-01-01

    Chronic lymphocytic leukemia is a heterogeneous yet incurable disease. Whole genome and - exome sequencing studies have revealed recurrently occurring somatic mutations in some genes. Several other prognostic markers have previously been tested for their prognostic value in CLL. LPL is among...... these markers. AIM: To evaluate LPL gene expression together with the well-established prognostic markers of CLL and investigate correlations with more recently identified prognostic markers, NOTCH1 and TP53 mutations. METHODS: On 149 patients LPL gene expression was analyzed by real-time RT-PCR. Exon 34...... and new prognostic markers, 3 out of 4 patients, who received treatment within 24 months after diagnosis, were LPL+ (p=0.03). There was a strong correlation between NOTCH1 mutation and LPL+ (p=0.005). The unfavorable prognosis of LPL+ was maintained in CLL with wild-type NOTCH1. CONCLUSIONS: NOTCH1...

  18. ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

    Science.gov (United States)

    Xiao, Hong-Bo; Wang, Ji-Ying; Sun, Zhi-Liang

    2017-12-01

    Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Leptin im Knochenstoffwechsel

    Directory of Open Access Journals (Sweden)

    Vock L

    2003-01-01

    Full Text Available Leptin ist ein in Adipozyten exprimiertes Hormon mit vielfältigen Funktionen im gesamten Organismus. Verschiedene Studien legen eine positive Wirkung von Leptin auf den Knochenstoffwechsel nahe. In vitro führte die Inkubation von Knochenmarkstromazellen mit Leptin zu deren Differenzierung zu Osteoblasten und Mineralisation der Matrix. Bei ovarektomierten Ratten konnte durch Leptin der Knochenverlust vermindert werden. Überraschenderweise zeigten andere Studien eine zentrale inhibitorische Wirkung von Leptin auf Osteoblasten bei Nagern. Diese einander scheinbar widersprechenden Ergebnisse zeigen, daß die molekularen Mechanismen, mit welchen Leptin auf den Knochenstoffwechsel wirkt, noch nicht ausreichend verstanden werden. In klinischen Studien findet sich eine protektive Wirkung von Fettmasse und "body mass index" (BMI auf die Knochendichte (postmenopausaler Frauen überwiegend bestätigt. Damit im Einklang, konnten erhöhte Leptinspiegel gefunden werden. Ob Leptin nun direkt in den Knochenstoffwechsel eingreift oder bloß indirekt etwa über eine erhöhte mechanische Belastung, läßt sich aus klinischen Studien allein nicht beantworten. Hingegen dürfte Leptin im Knochenstoffwechsel von Männern keine oder nur eine untergeordnete Rolle spielen. Die Situation bei Kindern und Jugendlichen ist noch unklar, wobei eine positive Wirkung von Leptin in fetalem Knochen relativ sicher ist. Leptin könnte jedoch auch im Wachstum und der Knochenreifung bei Kindern und Jugendlichen eine Rolle spielen.

  20. A novel nontruncating APOB gene mutation, R463W, causes familial hypobetalipoproteinemia.

    Science.gov (United States)

    Burnett, John R; Shan, Jing; Miskie, Brooke A; Whitfield, Amanda J; Yuan, Jane; Tran, Khai; McKnight, C James; Hegele, Robert A; Yao, Zemin

    2003-04-11

    Familial hypobetalipoproteinemia (FHBL), an autosomal co-dominant disorder, is associated with reduced plasma concentrations (<5th percentile for age and sex) of apolipoprotein (apo) B and beta-migrating lipoproteins. To date, only mutations in APOB encoding prematurely truncated apoB have been found in FHBL. We discovered a novel APOB gene mutation, namely R463W, in an extended Christian Lebanese FHBL kindred. Heterozygotes for R463W had the typical FHBL phenotype, whereas homozygotes had barely detectable apoB-100. The effect of the R463W mutation on apoB secretion was examined using transfected McA-RH7777 cells that expressed one of two recombinant human apoBs, namely B48 and B17. In both cases, the mutant proteins (B48RW and B17RW) were retained within the endoplasmic reticulum and were secreted poorly compared with their wild-type counterparts. Pulse-chase analysis showed that secretion efficiencies of B48RW and B17RW were, respectively, 45 and 40% lower than those of the wild-types. Substitution of Arg(463) with Ala in apoB-17 (B17RA) decreased secretion efficiency by approximately 50%, but substitution with Lys (B17RK) had no effect on secretion, indicating that the positive charge was important. Molecular modeling of apoB predicted that Arg(463) was in close proximity to Glu(756) and Asp(456). Substitution of Glu(756) with Gln (B17EQ) had no effect on secretion, but substitution of Asp(456) with Asn (B17DN) decreased secretion to the same extent as B17RW. In co-transfection experiments, the mutant B17RW showed increased binding to microsomal triglyceride transfer protein as compared with wild-type B17. Thus, the naturally occurring R463W mutant reveals a key local domain governing assembly and secretion of apoB-containing lipoproteins.

  1. The APOB insertion/deletion polymorphism (rs17240441) influences postprandial lipaemia in healthy adults

    OpenAIRE

    Vimaleswaran, Karani Santhanakrishnan; Minihane, Anne M; Li, Yue; Gill, Rosalyn; Lovegrove, Julie A; Williams, Christine M; Jackson, Kim G

    2015-01-01

    BACKGROUND: \\ud Apolipoprotein (apo)B is the structural apoprotein of intestinally- and liver- derived lipoproteins and plays an important role in the transport of triacylglycerol (TAG) and cholesterol. Previous studies have examined the association between the APOB insertion/deletion (ins/del) polymorphism (rs17240441) and postprandial lipaemia in response to a single meal; however the findings have been inconsistent with studies often underpowered to detect genotype-lipaemia associations, f...

  2. Serum ApoB levels in depressive patients: associated with cognitive deficits.

    Science.gov (United States)

    Hui, Li; Han, Mei; Du, Xiang Dong; Zhang, Bao Hua; He, Shu Chang; Shao, Tian Nan; Yin, Guang Zhong

    2017-01-05

    Cognitive deficits have been regarded as one of the most significant clinical symptoms of depressive disorder. Accumulating evidence has shown that apolipoprotein B (ApoB) levels, which are responsible for inducing neurodegeneration, may be involved in cognitive deficits. This study examines cognitive deficits, and the correlation of serum ApoB levels with cognitive deficits of depressive disorder. 90 depressive patients and 90 healthy controls with matched age and gender were recruited. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum ApoB levels in depressive patients were measured by immunoturbidimetric method. Our results showed that depressive patients had lower scores of cognition including RBANS total score and subscales of language and delayed memory (all, p cognitive functions also passed Bonferroni corrections. Serum ApoB levels were negatively correlated with delayed memory score in depressive patients (r = -0.30, p = 0.01). Furthermore, stepwise multivariate regression analysis indicated that serum ApoB levels independently contributed to delayed memory in depressive patients (t = -2.68, p = 0.01). Our findings support that serum ApoB levels may be involved in delayed memory decline in depressive patients. Depressive patients also experience greater cognitive deficits, especially in delayed memory and language than healthy controls.

  3. Leptin, obesity and cardiovascular disease.

    Science.gov (United States)

    Correia, Marcelo Lima de Gusmao; Haynes, William Geoffrey

    2004-03-01

    Obesity is a risk factor for cardiovascular diseases. Leptin levels are increased in obesity and leptin exhibits cardiovascular actions that may contribute to increased cardiovascular risk. We review the sympathetic, renal and vascular actions of leptin and their relevance to cardiovascular disease. Leptin possesses cardio-renal actions potentially contributing to obesity-related hypertension including generalized sympathoactivation. However, given that leptin resistance occurs in obesity, it has been difficult to link hyperleptinemia with hypertension. One possibility is that leptin resistance is confined to the metabolic effects of leptin, with preservation of its sympathoexcitatory actions. Other mechanisms may contribute to the pressor effects of leptin. For instance, angiotensin II induces leptin generation. Leptin also potentiates the pressor effect of insulin. Therefore, interactions between angiotensin II and insulin with leptin could have deleterious cardiovascular effects in obesity. Additionally, leptin appears to stimulate vascular inflammation, oxidative stress and hypertophy. These actions may contribute to the pathogenesis of hypertension, atherosclerosis, and left ventricular hypertrophy. The potential actions of leptin in the pathophysiology of cardiovascular complications of obesity are diverse, despite evidence of leptin resistance to its metabolic actions. However, most information about cardiovascular actions of leptin derives from in-vitro and animal studies. Future research in humans is widely awaited.

  4. Undaria pinnatifida soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.

    Science.gov (United States)

    Xiao, Hong-Bo; Lu, Xiang-Yang; Zhang, Heng-Bo; Sun, Zhi-Liang; Fang, Jun

    2013-12-01

    Angiopoietin-like protein 3 (Angptl3)-lipoprotein lipase (LPL) pathway may be a useful pharmacologic target for hyperlipidemia. The present study was conducted to test the effect of soluble fiber extracted from Undaria pinnatifida (UP), on hyperlipidemia in apolipoprotein E-deficient (ApoE(-/-)) mice. Forty mice were divided into four groups (n = 10): control group (C57BL/6J mice), ApoE(-/-) mice group, and two groups of ApoE(-/-) mice treated with UP fiber (5 or 10 % per day). UP soluble fiber treatment significantly decreased plasma and hepatic total cholesterol, triglycerides levels, plasma low-density lipoprotein cholesterol, and malondialdehyde concentrations and increased plasma high-density lipoprotein cholesterol level and downregulated protein expression of Angptl3 concomitantly with upregulated protein expression of LPL. In addition, T0901317 caused elevated expression of hepatic Angptl3 protein, and the effect of T0901317 was also abrogated by UP soluble fiber in C57BL/6J mice. The present results suggest that the UP soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.

  5. Nutritional modification of SCD, ACACA and LPL gene expressions in different ovine tissues

    Directory of Open Access Journals (Sweden)

    K. Ropka-Molik

    2017-07-01

    Full Text Available Fatty acid composition is one of the main factors affecting health benefits of food. Stearoyl-CoA desaturase 1 (SCD, acetyl-CoA carboxylase alpha (ACACA and lipoprotein lipase (LPL have been considered as the rate-limiting enzymes in the biosynthesis of different fatty acids critical in lipid metabolism. The aim of our study was the analysis of differences in expression profiles of three ovine genes related to lipid metabolism (LPL, ACACA, SCD depending on feeding system and tissue type. The gene expression measurement was performed using a real-time PCR method on 60 old-type Polish Merino Sheep, which were divided into three feeding groups (I – complete pellet mixture, n =  12; II – complete mixture with addition of fresh grass, n =  24; III – complete mixture with addition of fresh red clover, n =  24. From all lambs, tissue samples – subcutaneous fat, perirenal fat and liver – were collected immediately after slaughter and LPL, ACACA and SCD expression was estimated based on two endogenous controls (RPS2 – ribosomal protein S2; ATP5G2 – H(+-transporting ATP synthase. Our research indicated that supplementation of diet with an addition of fresh grass or red clover significantly (P < 0.05 decreased the expression of SCD, ACACA and LPL genes in fat tissue compared to standard complete pelleted mixture. On the other hand, the highest expression of ACACA was detected in liver tissue collected from sheep fed a diet with an addition of fresh red clover (P < 0.05. In turn, the highest expression of the SCD gene was detected in animals fed with grass supplementation (P < 0.05. Regardless of diet supplementation, the highest SCD transcript abundance was detected in perirenal fat, while LPL and ACACA expression was the highest in both perirenal and subcutaneous fat. The ability of nutrigenomic regulation of transcription of analyzed genes confirmed that these genes play a critical role in regulation of lipid

  6. Treatment with liraglutide may improve markers of CVD reflected by reduced levels of apoB

    DEFF Research Database (Denmark)

    Engelbrechtsen, Line; Lundgren, J; Wewer Albrechtsen, Nicolai Jacob

    2017-01-01

    on plasma lipid profiles and apoB. Methods: Fifty-eight individuals with obesity (body mass index 34.5 ± 3.0 kg/m2 [mean ± SD]) were included in this study. After 8 weeks on a very low-calorie diet (800 kcal/day), participants were randomized to weight maintenance with meal replacements with or without...

  7. Novel Molecular Aspects of Ghrelin and Leptin in the Control of Adipobiology and the Cardiovascular System

    Science.gov (United States)

    Rodríguez, Amaia

    2014-01-01

    Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH) causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca2+ increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies. PMID:24685565

  8. Correlation of the leptin

    DEFF Research Database (Denmark)

    Finucane, F; Luan, J; Wareham, N

    2009-01-01

    AIMS/HYPOTHESIS: Obesity is the dominant cause of insulin resistance. In adult humans it is characterised by a combination of adipocyte hypertrophy and, to a lesser extent, adipocyte hyperplasia. As hypertrophic adipocytes secrete more leptin and less adiponectin, the plasma leptin......:adiponectin ratio (LAR) has been proposed as a potentially useful measure of insulin resistance and vascular risk. We sought to assess the usefulness of the LAR as a measure of insulin resistance in non-diabetic white adults. METHODS: Leptin and adiponectin levels were measured in 2,097 non-diabetic individuals...... from the Ely and European Group for the Study of Insulin Resistance (EGIR) Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study cohorts. LAR was compared with fasting insulin and HOMA-derived insulin sensitivity (HOMA-S) in all individuals and with the insulin sensitivity index...

  9. MicroRNA-134 Promotes the Development of Atherosclerosis Via the ANGPTL4/LPL Pathway in Apolipoprotein E Knockout Mice.

    Science.gov (United States)

    Ye, Qiong; Tian, Guo-Ping; Cheng, Hai-Peng; Zhang, Xin; Ou, Xiang; Yu, Xiao-Hua; Tan, Ru-Qi; Yang, Feng-Yun; Gong, Duo; Huang, Chong; Pan, Yan-Jun; Zhang, Jie; Chen, Ling-Yan; Zhao, Zhen-Wang; Xie, Wei; Li, Liang; Zhang, Min; Xia, Xiao-Dan; Zheng, Xi-Long; Tang, Chao-Ke

    2018-03-01

    Atherosclerosis is the most common cause of cardiovascular disease, such as myocardial infarction and stroke. Previous study revealed that microRNA (miR)-134 promotes lipid accumulation and proinflammatory cytokine secretion through angiopoietin-like 4 (ANGPTL4)/lipid lipoprotein (LPL) signaling in THP-1 macrophages. ApoE KO male mice on a C57BL/6 background were fed a high-fat/high-cholesterol Western diet, from 8 to 16 weeks of age. Mice were divided into four groups, and received a tail vein injection of miR-134 agomir, miR-134 antagomir, or one of the corresponding controls, respectively, once every 2 weeks after starting the Western diet. After 8 weeks we measured aortic atherosclerosis, LPL Activity, mRNA and protein levels of ANGPTL4 and LPL, LPL/ low-density lipoprotein receptor related protein 1 Complex Formation, proinflammatory cytokine secretion and lipid levels. Despite this finding, the influence of miR-134 on atherosclerosis in vivo remains to be determined. Using the well-characterized mouse atherosclerosis model of apolipoprotein E knockout, we found that systemic delivery of miR-134 agomir markedly enhanced the atherosclerotic lesion size, together with a significant increase in proinflammatory cytokine secretion and peritoneal macrophages lipid contents. Moreover, overexpression of miR-134 decreased ANGPTL4 expression but increased LPL expression and activity in both aortic tissues and peritoneal macrophages, which was accompanied by increased formation of LPL/low-density lipoprotein receptor-related protein 1 complexes in peritoneal macrophages. However, an opposite effect was observed in response to miR-134 antagomir. These findings suggest that miR-134 accelerates atherogenesis by promoting lipid accumulation and proinflammatory cytokine secretion via the ANGPTL4/LPL pathway. Therefore, targeting miR-134 may offer a promising strategy for the prevention and treatment of atherosclerotic cardiovascular disease.

  10. Monitoring leptin activity using the chicken leptin receptor.

    Science.gov (United States)

    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.

  11. Circulating leptin and thyroid dysfunction

    DEFF Research Database (Denmark)

    Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

    2003-01-01

    the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state...... relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine...... hormone involvement in thermogenesis and regulation of uncoupling proteins. In this review, we have focused on leptin in relation to thyroid pathophysiology....

  12. Leptin controls hair follicle cycling.

    Science.gov (United States)

    Watabe, Reiko; Yamaguchi, Takashi; Kabashima-Kubo, Rieko; Yoshioka, Manabu; Nishio, Daisuke; Nakamura, Motonobu

    2014-04-01

    Leptin is a cytokine well known for its ability to control body weight and energy metabolism. Several lines of evidence have recently revealed that leptin also plays an important role in wound healing and immune modulation in skin. Sumikawa et al. Exp Dermatol 2014 evaluated the effect of leptin on hair follicle cycling using mutant and wild-type mice. They report that leptin is produced in dermal papilla cells in hair follicles and that leptin receptor-deficient db/db mice show an abnormality in hair follicle cycling. Moreover, leptin injection induced the transition into the growth stage of the hair cycle (anagen). On this basis, it now deserves exploration whether leptin-mediated signalling is a key stimulus for anagen induction and whether this may be targeted to manage human hair disorders with defect in the control of hair follicle cycling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Leptin: a cardiovascular perspective

    African Journals Online (AJOL)

    Review Article: Leptin: a cardiovascular perspective. 72. 2012 Volume 17 No 2. JEMDSA. Introduction. Within the realms of noncommunicable disease development in South Africa, obesity is a disease that causes concern. This especially holds true for type 2 diabetes and cardiovascular diseases. Disheartened.

  14. Novel APOB missense variants, A224T and V925L, in a black South African woman with marked hypocholesterolemia.

    Science.gov (United States)

    Miller, Sharon A; Hooper, Amanda J; Mantiri, George A; Marais, David; Tanyanyiwa, Donald M; McKnight, James; Burnett, John R

    2016-01-01

    One genetic cause of markedly low plasma concentrations of apolipoprotein (apo) B and low density lipoprotein (LDL)-cholesterol is familial hypobetalipoproteinemia. We aimed to determine the molecular basis for the marked hypocholesterolemia consistent with heterozygous familial hypobetalipoproteinemia in a black female subject of Xhosa lineage. Coding regions of APOB, MTTP, PCSK9,ANGPTL3, SAR1B and APOC3 were sequenced, and APOE was genotyped. COS-7 cells were transfected with plasmids containing apoB variants. Western blotting was used to detect cellular and secreted apoB, and co-immunoprecipitation performed to assess binding with the microsomal triglyceride transfer protein (MTP). Sequence analysis of the APOB gene revealed her to be heterozygous for two novel variants, c.751G>A (A224T) and c.2854G>C (V925L). She was also homozygous for the APOEε2 allele, and did not carry a PCSK9 loss-of-function mutation. Although Ala(224) is within the postulated MTP binding region in apoB, it is not conserved among mammalian species. Subsequent genotyping showed that Ala224Thr is found in a southern African population (n=654) with an allele frequency of 1.15% and is not associated with plasma lipid levels. Val(925), like Ala(224), is within the N-terminal 1000 amino acids required for lipoprotein assembly, but was not found in the population screen. However, in vitro studies showed that apoB V925L did not affect apoB48 production or secretion nor have a deleterious effect on MTP interaction with apoB. Taken together, this suggests that the hypocholesterolemia in our case may be a result of being homozygous for APOEε2 with a low baseline cholesterol. Copyright © 2016 National Lipid Association. All rights reserved.

  15. Post-heparin LPL activity measurement using VLDL as a substrate: a new robust method for routine assessment of plasma triglyceride lipolysis defects.

    Directory of Open Access Journals (Sweden)

    Mathilde Di Filippo

    Full Text Available BACKGROUND: Determination of lipoprotein lipase (LPL activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles. METHODS: Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.15. Following incubation at 37°c, the NEFA (non esterified fatty acids produced were assayed hourly for 4 hours. LPL activity was expressed as µmol/l/min after subtraction of hepatic lipase (HL activity, obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients. RESULTS: Our method was reproducible (coefficient of variation (CV: intra-assay 5.6%, inter-assay 7.1%, and tightly correlated with the conventional radiolabelled triolein emulsion method (n = 26, r = 0.88. Normal values were established at 34.8 ± 12.8 µmol/l/min (mean ± SD from 20 control subjects. LPL activities obtained from 71 patients with documented history of major hypertriglyceridemia showed a trimodal distribution. Among the 11 patients with a very low LPL activity (10 µmol/l/min. CONCLUSION: This new reproducible method is a valuable tool for routine diagnosis and reliably identifies LPL activity defects.

  16. Post-heparin LPL activity measurement using VLDL as a substrate: a new robust method for routine assessment of plasma triglyceride lipolysis defects.

    Directory of Open Access Journals (Sweden)

    Mathilde Di Filippo

    Full Text Available Determination of lipoprotein lipase (LPL activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles.Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.15. Following incubation at 37°c, the NEFA (non esterified fatty acids produced were assayed hourly for 4 hours. LPL activity was expressed as µmol/l/min after subtraction of hepatic lipase (HL activity, obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients.Our method was reproducible (coefficient of variation (CV: intra-assay 5.6%, inter-assay 7.1%, and tightly correlated with the conventional radiolabelled triolein emulsion method (n = 26, r = 0.88. Normal values were established at 34.8 ± 12.8 µmol/l/min (mean ± SD from 20 control subjects. LPL activities obtained from 71 patients with documented history of major hypertriglyceridemia showed a trimodal distribution. Among the 11 patients with a very low LPL activity ( 10 µmol/l/min.This new reproducible method is a valuable tool for routine diagnosis and reliably identifies LPL activity defects.

  17. Monoclonal Antibodies That Bind to the Ly6 Domain of GPIHBP1 Abolish the Binding of LPL

    DEFF Research Database (Denmark)

    Hu, Xuchen; Sleeman, Mark W; Miyashita, Kazuya

    2017-01-01

    GPIHBP1, an endothelial cell protein, binds lipoprotein lipase (LPL) in the interstitial spaces and shuttles it to its site of action inside blood vessels. For years, studies of human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned that monoclonal antibodies (mAbs) agai...

  18. The complete genome sequence of Lactobacillus plantarum LPL-1, a novel antibacterial probiotic producing class IIa bacteriocin.

    Science.gov (United States)

    Wang, Yao; Shang, Nan; Qin, Yuxuan; Zhang, Ying; Zhang, Jinlan; Li, Pinglan

    2018-01-20

    Bacteriocins are antibacterial proteins or peptides synthesized by ribosomes to inhibit or kill both closely related and non-related bacterium. Class IIa bacteriocins possess high activity against foodborne pathogen Listeria monocytogenes. A novel strain Lactobacillus plantarum LPL-1 was isolated from fermented fish and considered as a bacteriocin producing probiotic with great antibacterial activity against Listeria monocytogenes 54002. The complete genome of L. plantarum LPL-1 contains one circular chromosome and plasmid. According to the genome, biosynthetic genes of bacteriocin including precursor, immunity protein,accessory protein and transporter protein were identified; and biosynthetic mechanism of class IIa bacteriocin was also further analyzed. The antibacterial activity of purified bacteriocin against L.monocytogenes54002 was determined and the diameter of inhibition zone was about 16.6 mm by vernier caliper. This work provided the complete genome information of L. plantarum LPL-1 that could benefit for understanding the biosynthetic mechanism of class IIa bacteriocin as well as the potential application of L. plantarum LPL-1 in nutraceutical and pharmaceutical. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Identification of apoB-100 Peptide-Specific CD8+ T Cells in Atherosclerosis.

    Science.gov (United States)

    Dimayuga, Paul C; Zhao, Xiaoning; Yano, Juliana; Lio, Wai Man; Zhou, Jianchang; Mihailovic, Peter M; Cercek, Bojan; Shah, Prediman K; Chyu, Kuang-Yuh

    2017-07-15

    T cells are found in atherosclerotic plaques, with evidence supporting a potential role for CD8+ T cells in atherogenesis. Prior studies provide evidence of low-density lipoprotein and apoB-100 reactive T cells, yet specific epitopes relevant to the disease remain to be defined. The current study was undertaken to identify and characterize endogenous, antigen-specific CD8+ T cells in atherosclerosis. A peptide fragment of apoB-100 that tested positive for binding to the mouse MHC-I allele H2K b was used to generate a fluorescent-labeled H2K b pentamer and tested in apoE -/- mice. H2K b pentamer(+)CD8+ T cells were higher in apoE -/- mice fed an atherogenic diet compared with those fed a normal chow. H2K b pentamer (+)CD8+ T cells in atherogenic diet-fed mice had significantly increased effector memory phenotype with a shift in Vβ profile. H2K b pentamer blocked lytic activity of CD8+ T cells from atherogenic diet-fed mice. Immunization of age-matched apoE -/- mice with the apoB-100 peptide altered the immune-dominant epitope of CD8+ T cells and reduced atherosclerosis. Our study provides evidence of a self-reactive, antigen-specific CD8+ T-cell population in apoE -/- mice. Immune modulation using the peptide antigen reduced atherosclerosis in apoE -/- mice. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  20. Circulating leptin and thyroid dysfunction

    DEFF Research Database (Denmark)

    Zimmermann-Belsing, Tina; Brabant, Georg; Holst, Jens Juul

    2003-01-01

    the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state....... It is not clear whether leptin and the melanocortin pathways interact with the thyroid axis under physiological conditions other than during starvation or in response to severe illness, both states in which the hypothalamo-pituitary-thyroid axis may be severely suppressed. In addition to the suggested central...... relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine...

  1. ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    Full Text Available BACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-Apob(100/100. CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome.

  2. High-resolution melting curve analysis of the ADSL and LPL genes and their correlation with meat quality and blood parameters in chickens.

    Science.gov (United States)

    Zhang, X D; Li, Q H; Lou, L F; Liu, J; Chen, X H; Zhang, C X; Wang, H H

    2015-03-20

    Adenylosuccinate lyase (ADSL) and lipoprotein lipase (LPL) are key enzymes in the metabolism of inosine monophosphate (IMP) and fat mass, which are important factors in meat quality evaluation. In this study, we selected 50 hens from the ISA B-line layers and Guangxi Yellow chickens, slaughtered the chickens at 120 days old, and analyzed polymorphisms in the ADSL and LPL genes using the high-resolution melting curve method. Blood lipid parameters, intramuscular fat (IMF), and IMP content were higher (P ADSL gene, a C3484T mutation was identified. In both breeds, the CC genotype showed the highest IMP, and IMP was the lowest in the TT genotype. In the 5ꞌ regulatory region of the LPL gene, a C293T mutation was identified. In both breeds, the CC genotype showed the lowest LPL and IMF, while IMF was the highest in the TT genotype. The percentages of individuals with the TT type in the ADSL gene, which was associated with the lowest IMP, were 16.0 and 52.0% in Guangxi chickens and ISA layers, respectively. The percentages of individuals with the CC type of the LPL gene, which was associated with the lowest LPL and IMF, were 28.0 and 44.0%, respectively. The ADSL and LPL gene mutations are correlated with differences in meat quality in different chicken breeds, and high-resolution melting curve is an effective prediction technology for these mutations.

  3. 1,3,5,8-tetrahydroxyxanthone regulates ANGPTL3-LPL pathway to lessen the ketosis in mice.

    Science.gov (United States)

    Xiao, Hong-Bo; Sun, Zhi-Liang; Zhou, Nan

    2012-05-12

    Ketosis is a metabolic disorder closely associated with both lipid and carbohydrate metabolism. Recent studies show that angiopoietin-like protein 3 (ANGPTL3) contributes to the development of metabolic disorder. The objective of this study was to explore the inhibitory effect of 1,3,5,8-tetrahydroxyxanthone (Xan), a naturally occurring flavonoid compound, on ketosis and the mechanisms involved in this regulation. After 4weeks, Xan (10 or 30mg/kg, intragastrically) treatment decreased plasma total ketone bodies, malondialdehyde, 8-isoprostane, triglyceride, total cholesterol levels, and hepatic ANGPTL3 expression concomitantly with increased plasma glucose concentration and adipose lipoprotein lipase (LPL) expression in ketosis murine. The present results suggest that Xan regulates ANGPTL3-LPL pathway to lessen the ketosis in mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and Inhibiting HMGCS2.

    Science.gov (United States)

    Kang, Dong Young; S P, Nipin; Darvin, Pramod; Joung, Youn Hee; Byun, Hyo Joo; Do, Chang Hee; Park, Kyung Do; Park, Mi Na; Cho, Kwang Hyun; Yang, Young Mok

    2017-07-03

    Ketogenesis is the production of ketone bodies, which provide energy when the body lacks glucose. Under ketogenic conditions, the body switches from primarily carbohydrate to fat metabolism to maintain energy balance. However, accumulation of high levels of ketone bodies in the blood results in ketosis. Treating ketosis with natural substances is preferable, because they are unlikely to cause side-effects. Momilactone B is an active compound isolated from Korean rice. Based on previous studies, we hypothesized that momilactone B could inhibit ketosis. We constructed an in vitro ketosis model by glucose starvation. We used this model to test the anti-ketosis effects of momilactone B. A primary target for treating ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down stored fat to produce triglycerides. We showed that momilactone B could regulate the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B suppressed the expression of HMGCS2 through the increased expression of STAT5b. We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.

  5. Leptin and bone mineral density

    DEFF Research Database (Denmark)

    Morberg, Cathrine M.; Tetens, Inge; Black, Eva

    2003-01-01

    .001). An inverse relation between BMD adjusted for body weight and serum leptin emerged in both the control group (r = -0.186; P multiple linear regression, fat mass, lean body mass, and occupational physical activity were positively associated...

  6. Leptin increases prostate cancer aggressiveness.

    Science.gov (United States)

    López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

    2011-12-01

    Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

  7. Leptin levels in infertile males

    International Nuclear Information System (INIS)

    Jahan, S.; Bibi, R.; Ahmed, S.

    2011-01-01

    Objective: To determine the leptin levels in the serum of normal, sub fertile and infertile men. Study Design: Analytical study. Place and Duration of Study: Department of Animal Sciences Quaid-e-Azam University, Islamabad, National Institute of Health (NIH), Islamabad and Dr. Salma and Kafeel Medical Centre, Islamabad, from April to December 2009. Methodology: Serum leptin levels hormonal concentrations (LH, FSH and testosterone) were determined by EIA in 154 males including 24 (15.58%) fertile, 19 (12.34%) polyzoospermic (PZs), 26 (16.88%) teratozoospermic (TZs), 27 (17.53%) astheno-teratozoospermic (ATZs), 18 (11.69%) oligozoospermic (OZs), 18 (11.69%) oligo-astheno-teratozoospermic (OATZs), 11 (7.14%) obstructive azoospermic (OBST-AZOOs) and 11 (7.14%) non-obstructive azoospermic (NON-OBST-AZOOs). BMI was also determined, divided into groups of greater than 24. Hormonal concentrations were compared by ANOVA and correlation was performed by using Graph pad prism version 5. Results: Significantly high levels of leptin concentrations were found in fertile (p 24 compared to fertile and infertile male patients with BMI 24. Leptin showed a significant positive correlation with LH (p < 0.01) and FSH (p < 0.002) and a significant negative correlation with testosterone (p < 0.001). Conclusion: Abnormal leptin level was significantly associated with fertility problems in males. Providing a link between leptin and reproduction factors contributing in control of testosterone and gonadotropins secretion in many aspects depending on fertility status in male subjects. BMI appears to have significant association with serum leptin levels. (author)

  8. Leptin as local inflammatory marker in COPD.

    Science.gov (United States)

    Broekhuizen, R; Vernooy, J H J; Schols, A M W J; Dentener, M A; Wouters, E F M

    2005-01-01

    Chronic inflammation of the lung is a characteristic finding in chronic obstructive pulmonary disease (COPD). Leptin is a pleiotropic cytokine thought to play a role in host response to inflammation. As recent studies have shown that leptin receptors are present in the lung, this study aimed to determine if leptin is detectable in induced sputum of COPD patients and if there is a relationship between leptin and other inflammatory markers in sputum. Sputum was induced in 14 male patients with moderate COPD (FEV1: 56 (15) % pred.). Leptin, total tumour necrosis factor (TNF)-alpha, and C-reactive protein (CRP) were analyzed in induced sputum supernatant by ELISA. Leptin was also determined in EDTA plasma. Leptin was detectable in induced sputum of 10 COPD patients. A significant relationship was found between sputum leptin and CRP (r = 0.943, P leptin and sputum leptin were inversely correlated (r = -0.643, P leptin is detectable in induced sputum of patients with moderate COPD and is related to other inflammatory markers. The observed correlations between leptin and inflammatory markers in sputum may indicate that leptin is involved in the local inflammatory response in COPD.

  9. Genetics Home Reference: leptin receptor deficiency

    Science.gov (United States)

    ... People with leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production ... weight gain associated with this disorder. Because hypogonadotropic hypogonadism occurs in leptin receptor deficiency , researchers suggest that ...

  10. Genetics Home Reference: congenital leptin deficiency

    Science.gov (United States)

    ... Description Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. ... are unknown. Congenital leptin deficiency is a rare cause of obesity. Researchers are studying the factors involved in more ...

  11. Serum leptin and insulin tests in obesity

    International Nuclear Information System (INIS)

    Yang Yin; Jiang Xiaojin; Leng Xiumei

    2001-01-01

    Objective: To study the clinical significance and the relations of leptin and insulin on obesity group. Methods: Leptin and insulin were tested with radioimmunoassay (RIA) in pre-obesity group and obesity group respectively. Results: Serum leptin and insulin levels were significantly elevated in obesity group compare with the controls (P<0.01). Conclusion: Changing with insulin, the elevation of leptin in obesity group has been identified as an important agent of diabetes mellitus (DM)

  12. Studies on leptin utilizing to obesity

    International Nuclear Information System (INIS)

    Zhao Minghui

    2001-01-01

    Leptin is a hormone synthesized and secreted by lipid cells. It is a product encoded and expressed by the obese gene. Administration of recombinant leptin decreases food intake, increases energy expenditure and promotes weight loss. Most studies indicate that leptin is a main regulating factor of catabolism and anabolism of adipose tissue. The circulating leptin level is a sensitive index which indicates the confusion of the rate of lipid metabolism such as hyperlipemia, lipo-liver and so on. The human leptin radioimmunoassay has been developed to quantitate human leptin in plasma or serum, and to further investigate the relationship between serum leptin concentration and body fat, gender, age, sexual hormones, endocrine of insulin, etc. Especially, serum leptin concentrations are correlated with body-mass-index (BMI), suggesting that most obese persons are resistant to leptin; Those who are relatively deficient of leptin may become the good candidates of leptin treatment in the future. The discovery and application of leptin make the study of obesity, non-insulin dependent diabetes and other correlation diseases enter a new stage

  13. Genistein Precipitated Hypothyroidism, Altered Leptin and C ...

    African Journals Online (AJOL)

    Genistein Precipitated Hypothyroidism, Altered Leptin and C-Reactive Protein Synthesis in Pregnant Rats. ... Thyroid hormone, C-reactive protein (CRP) and leptin assay was carried using the blood samples. Leptin was also assayed in the placenta and amniotic fluid supernatant. Oral exposure of pregnant rats to genistein ...

  14. Leptin, adiponectin and pulmonary diseases.

    Science.gov (United States)

    Ali Assad, Nour; Sood, Akshay

    2012-10-01

    Adipose tissue produces leptin and adiponectin - energy-regulating adipokines that may also play a role in inflammatory pulmonary conditions, as suggested by some murine studies. Leptin and adiponectin and their respective receptors are expressed in the human lung. The association between systemic or airway leptin and asthma in humans is currently controversial, particularly among adults. The majority of the evidence among children however suggests that systemic leptin may be associated with greater asthma prevalence and severity, particularly among prepubertal boys and peripubertal/postpubertal girls. Systemic and airway leptin concentrations may also be disproportionately higher in chronic obstructive pulmonary disease (COPD) patients, particularly among women, and reflect greater airway inflammation and disease severity. Quite like leptin, the association between systemic and airway adiponectin and asthma in humans is also controversial. Some but not all studies, demonstrate that serum adiponectin concentrations are protective against asthma among premenopausal women and peripubertal girls. On the other hand, serum adiponectin concentrations are inversely associated with asthma severity among boys but positively associated among men. Further, systemic and airway adiponectin concentrations are higher in COPD patients than controls, as demonstrated by case-control studies of men. Systemic adiponectin is also positively associated with lung function in healthy adults but inversely associated with lung function in subjects with COPD. It is therefore possible that pro-inflammatory effects of adiponectin dominate under certain physiologic conditions and anti-inflammatory effects under others. The adipokine-lung disease literature has critical gaps that include a lack of adequately powered longitudinal or weight-intervention studies; inadequate adjustment for confounding effect of obesity; and unclear understanding of potential sex interactions. It is also uncertain

  15. Mapping of the human APOB gene to chromosome 2p and demonstration of a two-allele restriction fragment length polymorphism

    International Nuclear Information System (INIS)

    Huang, L.; Miller, D.A.; Bruns, G.A.P.; Breslow, J.L.

    1986-01-01

    ApoB is a large glycoprotein with an apparent molecular mass of 550 kDa on NaDodSO 4 /PAGE. Recently, apoB cDNA clones have been isolated from an expression library made with mRNA from a human hepatoma cell line. These clones, which were all 1.5-1.6 kilobases (kb) long and corresponded to the 3' end of apoB mRNA, were used to demonstrate that hepatic apoB mRNA is ≅ 22 kb long. In the current report, a probe derived from one of these cDNA clones, pB8, was used for in situ hybridization experiments to map the human gene for apoB, APOB, to the distal half of the short arm of chromosome 2. This probe was also used to analyze somatic cell hybrids and, in agreement with the in situ hybridization studies, concordancy was demonstrated with chromosome 2. In addition, two hybrids with chromosome 2 translocations that contain only the short arm reacted with the pB8 probe. A third hybrid with a complex rearrangement of chromosome 2, which deleted an interstitial region and the tip of the short arm of chromosome 2, did not react. These data indicate that APOB maps to either 2p21-p23 or 2p24-pter. In further studies, DNA from normal individuals, digested with the restriction endonuclease EcoRI and subjected to Southern blot analysis with the pB8 probe, revealed a two-allele restriction fragment length polymorphism (RFLP). The mapping studies provide the means for understanding the relationship of the APOB locus to others in the human genome, whereas the demonstration of an APOB RFLP increases their ability to assess the role of this locus in determining plasma lipoprotein levels

  16. Human skeletal muscle releases leptin in vivo

    DEFF Research Database (Denmark)

    Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

    2012-01-01

    Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

  17. Relevance of Serum Leptin and Leptin-Receptor Concentrations in Critically Ill Patients

    Directory of Open Access Journals (Sweden)

    Alexander Koch

    2010-01-01

    Full Text Available The adipocyte-derived cytokine leptin was implicated to link inflammation and metabolic alterations. We investigated the potential role of leptin components in critically ill patients, because systemic inflammation, insulin resistance, and hyperglycemia are common features of critical illness. Upon admission to Medical Intensive Care Unit (ICU, free leptin and soluble leptin-receptor serum concentrations were determined in 137 critically ill patients (95 with sepsis, 42 without sepsis and 26 healthy controls. Serum leptin or leptin-receptor did not differ between patients or controls and were independent of sepsis. However, serum leptin was closely associated with obesity and diabetes and clearly correlated with markers of metabolism and liver function. Leptin-receptor was an unfavourable prognostic indicator, associated with mortality during three years follow-up. Our study indicates a functional role of leptin in the pathogenesis of severe illness and emphasizes the impact of complex metabolic alterations on the clinical outcome of critically ill patients.

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

    Directory of Open Access Journals (Sweden)

    Ai-Fen Yan

    2016-05-01

    Full Text Available 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.

  19. Genetic variation at the ApoB 3' HVR minisatellite locus in the Mbenzele Pygmies from the Central African Republic.

    Science.gov (United States)

    Destro-Bisol, Giovanni; Belledi, Michele; Capelli, Cristian; Maviglia, Riccardo; Spedini, Gabriella

    2000-09-01

    This study analyzes the polymorphic minisatellite ApoB 3' HVR in the Mbenzele Pygmies from the Central African Republic. A total of 14 alleles was observed, with frequencies ranging from 0.020 (19, 21, 27, and 45 repeat unit alleles) to 0.210 (37 repeat unit allele). Departure from Hardy-Weinberg equilibrium was not statistically significant. The estimated heterozygosity was 0.874 +/- 0.016. Taking data from the literature into consideration, the results support the hypothesis that the Africans are different from non-Africans due to greater ApoB 3' HVR genetic diversity and a unimodal profile of ApoB 3' HVR allele frequency distribution. Interpopulational relationships were also analyzed using an F(ST) based genetic distance. The results highlight the similarity between the Mbenzele Pygmies and Bantu-speaking groups (Ewondo and Zulu), and the divergence between the Mbenzele and San, the two groups which are often considered to be the most direct descendants of proto-Africans. Am. J. Hum. Biol. 12:588-592, 2000. Copyright 2000 Wiley-Liss, Inc.

  20. LEPTIN AND OBESITY – NEUROENDOCRINE , METABOLIC AND ATHEROGENIC EFFECTS OF LEPTIN

    Directory of Open Access Journals (Sweden)

    Mišo Šabovič

    2003-01-01

    Full Text Available Background. Leptin is an adipocyte-derived hormone that was recently discovered. Leptin and leptin resistance play an important role in the pathogenesis of obesity. Leptin acts by binding to specific receptors in the hypothalamus to alter the expression of several neuropeptides that regulate food intake and energy expenditure. As commonly found, obese persons have leptin resistance and consequently attenuated effects of leptin. Mechanism underlying leptin resistance has not been explained yet: it might be the result of a receptor or post receptor defect, impaired transport of leptin through cerebrovascular barrier or inactivation of leptin by binding proteins. Phase I and II clinical trials proved that recombinant leptin administration to humans is safe. First results of the current phase III clinical trials demonstrated that leptin is moderately effective in the treatment of obesity.Conclusions. Beside anti-obesity effect, leptin can have important metabolic and neuroendocrine effects. It is involved in glucose metabolism and insulin secretion, pathogenesis of polymetabolic syndrome, diabetes and arterial hypertension. In addition it affects some processes of atherothrombosis. It interacts with and significantly influences hypothalamic-pituitaryadrenal, thyroid, sexual glands and growth hormone axes. Explaining the mechanism of leptin resistance could be important for understanding the pathogenesis of obesity and associated pathologic states as polymetabolic syndrom, diabetes, arterial hipertension and atherothrombosis.

  1. Gene Expression of Leptin and Long Leptin Receptor Isoform in Endometriosis: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Andrea Prestes Nácul

    2013-01-01

    Full Text Available In this study, leptin/BMI ratio in serum and peritoneal fluid and gene expression of leptin and long form leptin receptor (OB-RL were assessed in eutopic and ectopic endometria of women with endometriosis and controls. Increased serum leptin/BMI ratio was found in endometriosis patients. Leptin and OB-RL gene expression was significantly higher in ectopic versus eutopic endometrium of patients and controls. A positive, significant correlation was observed between leptin and OB-RL transcripts in ectopic endometria and also in eutopic endometria in endometriosis and control groups. A negative and significant correlation was found between OB-RL mRNA expression and peritoneal fluid leptin/BMI ratio only in endometriosis. These data suggest that, through a modulatory interaction with its active receptor, leptin might play a role in the development of endometrial implants.

  2. Mother and Infant Body Mass Index, Breast Milk Leptin and Their Serum Leptin Values

    Directory of Open Access Journals (Sweden)

    Francesco Savino

    2016-06-01

    Full Text Available Purpose: This study investigates correlations between mother and infant Body Mass Index (BMI, their serum leptin values and breast milk leptin concentration in early infancy. Subjects and Methods: We determined serum leptin values in 58 healthy infants and leptin values in their mothers’ breast milk, using radioimmunoassay (RIA. Infant and maternal anthropometrics were measured. Results: Median leptin concentration was 3.9 ng/mL (interquartile range (IQR: 2.75 in infant serum, 4.27 ng/mL (IQR: 5.62 in maternal serum and 0.89 ng/mL (IQR: 1.32 in breast milk. Median maternal BMI and weight were 24 kg/m2 (IQR: 4.41 and 64 kg (IQR: 15. Median infant BMI was 15.80 kg/cm2 (IQR: 4.02, while average weight was 5.130 kg (IQR: 1.627. Infants serum leptin values positively correlated with infants’ BMI (p = 0.001; r = 0.213 and breast milk leptin (p = 0.03; r = 0.285. Maternal serum leptin values positively correlated with maternal BMI (p = 0.000, r = 0.449 and breast milk leptin ones (p = 0.026; r = 0.322. Conclusion: Breast milk leptin and maternal BMI could influence infant serum leptin values. Further studies are needed to better elucidate the role of genetics and environment on infant leptin production and risk of obesity later in life.

  3. Adipocyte iron regulates leptin and food intake.

    Science.gov (United States)

    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.

  4. Physical activity modifies the effect of LPL, LIPC, and CETP polymorphisms on HDL-C levels and the risk of myocardial infarction in women of European ancestry.

    Science.gov (United States)

    Ahmad, Tariq; Chasman, Daniel I; Buring, Julie E; Lee, I-Min; Ridker, Paul M; Everett, Brendan M

    2011-02-01

    Recent genome-wide association studies have identified common variants associated with high-density lipoprotein cholesterol (HDL-C). Whether these associations are modified by physical activity, which increases HDL-C levels and reduces the risk of cardiovascular disease, is uncertain. In a prospective cohort study of 22 939 apparently healthy US women of European ancestry, we selected 58 single nucleotide polymorphisms (SNPs) in 9 genes that demonstrated genome-wide association (Pwomen, whereas the reverse was observed for rs10096633 at LPL. Minor-allele carrier status at the LPL SNP was associated with a reduced risk of myocardial infarction in active (hazard ratio, 0.51; 95% confidence interval 0.30-0.86) but not among inactive women (hazard ratio 1.13; 95% confidence interval 0.79 to 1.61; P-interaction=0.007). By contrast, carrier status at the CETP SNP was associated with a reduced risk of myocardial infarction regardless of activity level (hazard ratio, 0.72; 95% confidence interval, 0.57 to 0.92; P-interaction=0.71). No association between LIPC SNP carrier status and myocardial infarction risk was noted. The effects of common variants in the LPL, LIPC, and CETP genes on HDL-C levels are modified by physical activity. For a common variant in LPL, the impact on myocardial infarction varied by activity level, whereas the effects of a common variant in CETP on myocardial infarction risk did not.

  5. Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico

    Directory of Open Access Journals (Sweden)

    José Ángel Cahua-Pablo

    2015-09-01

    Full Text Available Metabolic syndrome (MetS is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD. Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR = 2.9; p = 0.013 in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04. Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006. In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001. In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.

  6. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism.

    Science.gov (United States)

    Park, Hyeong-Kyu; Ahima, Rexford S

    2015-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Effect Of Leptin Status On Neuroendocrine- Reproductive ...

    African Journals Online (AJOL)

    The brain of each rat was harvested and processed into whole homogenate, and was used for some biochemicals assays (i.e isolation and purification of RNA, reverse transcription polymerase chain reaction (PCR), and leptin assay). The results showed that insulin increased the secretion of leptin, which in turn, reduced ...

  8. The Effects of Leptin on Breastfeeding Behaviour

    Directory of Open Access Journals (Sweden)

    Anna M. Cannon

    2015-09-01

    Full Text Available 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.

  9. Thyroid hormone and leptin in the testis

    Directory of Open Access Journals (Sweden)

    Cristiane Fonte Ramos

    2014-11-01

    Full Text Available Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs. Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in humans and mice are leptin functions. It has been suggested that thyroid hormones (TH could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis.

  10. Leptin: A cardiovascular perspective | Schutte | Journal of ...

    African Journals Online (AJOL)

    The development of obesity, as well as resultant type 2 diabetes, hypertension and cardiovascular disease, is causing concern in South Africa. Following the discovery of leptin in 1994, hopes were raised that the manipulation of the leptin axis might yield successful therapy for obesity. Although hope still remains, the role of ...

  11. Polymorphism in leptin receptor gene was associated with obesity in ...

    African Journals Online (AJOL)

    Pramudji Hastuti

    2016-01-11

    Jan 11, 2016 ... Abstract Background: Leptin is a hormone that regulates homeostasis energy through the cen- tral–peripheral mechanism as well as regulates hunger and satiety. Leptin receptor is important in leptin signal transduction that is located mainly in the hypothalamus. The mutation in leptin receptor (LEPR) gene ...

  12. Polymorphism in leptin receptor gene was associated with obesity in ...

    African Journals Online (AJOL)

    Background: Leptin is a hormone that regulates homeostasis energy through the central– peripheral mechanism as well as regulates hunger and satiety. Leptin receptor is important in leptin signal transduction that is located mainly in the hypothalamus. The mutation in leptin receptor (LEPR) gene causes splicing ...

  13. [Role of leptin in human reproduction (anorexia, bulimia)].

    Science.gov (United States)

    Pilka, L; Rumpík, D; Pilka, R

    2012-12-01

    Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are presenting for normal reproductive functions. Future interventional studies involving leptin administration are excepted to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunctions associated with states of relative leptin deficiency or resistance.

  14. Diet-induced obese mice retain endogenous leptin action.

    Science.gov (United States)

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-02

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

    2005-01-01

    Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

  16. Leptin to adiponectin ratio in preeclampsia.

    Science.gov (United States)

    Khosrowbeygi, A; Ahmadvand, H

    2013-04-01

    The aim of the present study was to assess leptin/adiponectin ratio in preeclamptic patients compared with normal pregnant women. A cross-sectional study was designed. The study population consisted of 30 preeclamptic patients and 30 healthy pregnant women. Serum levels of total leptin and adiponectin were assessed using commercially available enzyme-linked immunosorbent assay methods. The one-way ANOVA and Student's t tests and Pearson's correlation analysis were used for statistical calculations. Levels of leptin and adiponectin were also adjusted for BMI. A p-value preeclamsia and imbalance between the adipocytokines could be involved in the pathogenesis of preeclampsia.

  17. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    Directory of Open Access Journals (Sweden)

    Valdivielso Pedro

    2010-04-01

    Full Text Available Abstract Background Hypertriglyceridemia (HTG is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years was genotyped for the LPL-HindIII (rs320, S447X (rs328, D9N (rs1801177 and N291S (rs268 polymorphisms, the APOA5-S19W (rs3135506 and -1131T/C (rs662799 variants, and the APOE polymorphism (rs429358; rs7412 using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L, including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p p p p p p p = 0.042 and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p p Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

  18. Association of the HindIII and S447X Polymorphisms in LPL Gene with Hypertension and Type 2 Diabetes in Mexican Families

    Directory of Open Access Journals (Sweden)

    Salvador Muñoz-Barrios

    2012-01-01

    Full Text Available Lipoprotein lipase (LPL is a key enzyme in lipid metabolismand is associatedwith obesity, dyslipidemias, hypertension (HTN and type 2 diabetes mellitus (T2DM. LPL gene polymorphisms can be related with the development of cardiovascular risk factors. The present study was conducted to analyze the relationship of the HindIII and S447X polymorphisms in LPL gene with cardiovascular risk factors in Mexican families. The study population comprised ninety members of 30 Mexican families, in which an index case had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical parameters. Screening for both polymorphisms was made by PCR-RFLPs. In the parents, both polymorphisms were in Hardy-Weinberg’s equilibrium. We found that the genotype T/T of HindIII was associated with diastolic blood pressure ≧ 85 mmHg (OR = 1.1; p = 0.011, whereas the genotype C/C of S447X was associated with systolic blood pressure ≧ 130 mmHg (OR = 1.2; p < 0.001, diastolic blood pressure ≧ 85 mmHg (OR = 1.3; p < 0.001, T2DM (OR = 1.3; p < 0.001 and with increase of total cholesterol (β = 23.6 mg/mL; p = 0.03. These data suggest that the HindIII and S447X LPL gene polymorphisms can confer susceptibility for the development of hypertension and T2DM in Mexican families.

  19. Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers.

    Science.gov (United States)

    Bruno, Andreina; Alessi, Marinella; Soresi, Simona; Bonanno, Anna; Riccobono, Loredana; Montalbano, Angela Marina; Albano, Giusy Daniela; Gjomarkaj, Mark; Profita, Mirella

    2011-01-01

    Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils. We measured the levels of leptin, tumor necrosis factor alpha (TNF-α) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry. In plasma of COPD patients, leptin was inversely correlated with TNF-α and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-α. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-α were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers. Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.

  20. 20 years of leptin: leptin and reproduction: past milestones, present undertakings, and future endeavors.

    Science.gov (United States)

    Chehab, Farid F

    2014-10-01

    The association between leptin and reproduction originated with the leptin-mediated correction of sterility in ob/ob mice and initiation of reproductive function in normal female mice. The uncovering of a central leptin pathway regulating food intake prompted the dissection of neuroendocrine mechanisms involving leptin in the metabolic control of reproduction. The absence of leptin receptors on GnRH neurons incited a search for intermediary neurons situated between leptin-responsive and GnRH neurons. This review addresses the most significant findings that have furthered our understanding of recent progress in this new field. The role of leptin in puberty was impacted by the discovery of neurons that co-express kisspeptin, neurokinin B, and dynorphin and these could act as leptin intermediates. Furthermore, the identification of first-order leptin-responsive neurons in the premammilary ventral nucleus and other brain regions opens new avenues to explore their relationship to GnRH neurons. Central to these advances is the unveiling that agouti-related protein/neuropeptide Y neurons project onto GnRH and kisspeptin neurons, allowing for a crosstalk between food intake and reproduction. Finally, while puberty is a state of leptin sensitivity, mid-gestation represents a state of leptin resistance aimed at building energy stores to sustain pregnancy and lactation. The mechanisms underlying leptin resistance in pregnancy have lagged; however, the establishment of this natural state is significant. Reproduction and energy balance are tightly controlled and backed up by redundant mechanisms that are critical for the survival of our species. It will be the goal of the following decade to shed new light on these complex and essential pathways. © 2014 Society for Endocrinology.

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

    Directory of Open Access Journals (Sweden)

    Nasser M. Rizk

    2015-01-01

    Full Text Available 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.

  2. Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution.

    Directory of Open Access Journals (Sweden)

    John A Hammond

    Full Text Available The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional

  3. Plasma leptin concentrations in newborns of diabetic and nondiabetic mothers.

    Science.gov (United States)

    Gross, G A; Solenberger, T; Philpott, T; Holcomb, W L; Landt, M

    1998-04-01

    Leptin plays an important role in regulating body composition through modulation of appetite and energy expenditure. We hypothesized that leptin levels in umbilical cord blood correlate with newborn body weight and habitus. We also hypothesized that infants of diabetic mothers would demonstrate altered leptin metabolism. Venous blood was sampled at birth from the umbilical cords of 105 infants (74 infants of nondiabetic mothers, and 31 infants of diabetic mothers). Thirty-nine mothers had plasma leptin concentrations measured. Analysis was done using Student's t-test, Pearson's correlation, and Spearman's correlation. Univariate/multivariate regression was used for analysis of factors associated with leptin concentration in umbilical cord plasma. Maternal and newborn characteristics were correlated with log leptin levels in umbilical venous plasma. Leptin concentration in umbilical cord plasma correlated best with birth weight for newborns of both nondiabetic and diabetic mothers (p relationship between umbilical cord leptin level and newborn birth weight, as well as maternal DM, but not with gestational age. Similarly, there was no significant correlation with maternal plasma leptin concentration. The strong correlation of leptin concentration in umbilical cord plasma with newborn birth weight, and the lack of significant correlation with maternal leptin plasma levels, suggest that normal fetal leptin metabolism reflects fetal size and/or body habitus independent of maternal leptin metabolism. On the other hand, the higher umbilical plasma levels in infants of diabetic mothers may reflect an influence of altered fetal insulin homeostasis on fetal leptin metabolism, and suggests that maternal diabetes may influence fetal leptin metabolism.

  4. Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients.

    Science.gov (United States)

    Hoogeveen, R C; Ballantyne, C M; Pownall, H J; Opekun, A R; Hachey, D L; Jaffe, J S; Oppermann, S; Kahan, B D; Morrisett, J D

    2001-10-15

    Sirolimus (Rapamune, rapamycin, RAPA) is a potent immunosuppressive drug that has reduced the rate of acute rejection episodes by more than 40% in phase III trials when added to an immunosuppression regimen of cyclosporine (CsA) and prednisone. However, RAPA treatment tends to increase lipid levels, particularly among patients with pre-existing hyperlipidemia. To identify the metabolic pathway(s) leading to RAPA-mediated hyperlipidemia, five patients with renal transplants maintained on CsA+/-prednisone+/- azathioprine (AZA) were studied before and after 6 weeks of treatment with RAPA (off RAPA and on RAPA, respectively). Each study patient was infused with a single bolus of [2H4]-lysine to derive metabolic parameters for apoB100-containing lipoproteins by using kinetic analysis based upon quantitation of isotopic enrichment by gas chromatography-mass spectrometry. Serial lipid measurements revealed that four patients displayed increased plasma triglyceride levels after RAPA treatment, which coincided with significantly higher plasma VLDL-apoB100 concentrations (21.7+/-12.1 mg/dl off RAPA vs. 38.7+/-14.8 mg/dl on RAPA, mean+/-SD, P<0.05). Kinetic analysis showed that the RAPA-induced increase in VLDL-apoB100 concentrations was due to a significant reduction in the fractional catabolic rate (FCR) of very low-density lipoprotein (VLDL) apoB100 (0.83+/-0.65 off RAPA vs. 0.24+/-0.10 on RAPA, mean+/-SD, P<0.05), rather than an enhanced VLDL-apoB100 synthesis. In one patient, RAPA treatment induced hypercholesterolemia but not hypertriglyceridemia. This hypercholesterolemia was due to elevated low-density lipoprotein (LDL) cholesterol levels, which coincided with a decreased FCR of LDL-apoB100. Heparin-induced lipoprotein lipase activity was significantly lower in the immunosuppressed hyperlipidemic patients than in normolipidemic controls. However, RAPA treatment did not significantly alter basal lipoprotein lipase activity in renal transplant patients in this study

  5. Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARgamma), Lipoprotein Lipase (LPL), Serum Lipid and HOMA-IR in Rats.

    Science.gov (United States)

    Yoke Yin, Chia; So Ha, Ton; Abdul Kadir, Khalid

    2010-01-01

    Studies on ligand binding potential of glycyrrhizic acid, a potential agonist to PPARgamma, displayed encouraging results in amelioration of metabolic syndrome. The regulation of gene cassettes by PPARgamma affects glucose homeostasis, lipid, lipoprotein metabolism and adipogenesis. This study was performed to determine the effects of GA on total PPARgamma and LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARgamma and LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles. Thus, oral administration of 100 mg/kg GA for 24 hours improved insulin sensitivity and lipid profiles and induced upregulation of total PPARgamma and LPL expression levels in all studied tissues.

  6. Effects of Glycyrrhizic Acid on Peroxisome Proliferator-Activated Receptor Gamma (PPARγ, Lipoprotein Lipase (LPL, Serum Lipid and HOMA-IR in Rats

    Directory of Open Access Journals (Sweden)

    Chia Yoke Yin

    2010-01-01

    Full Text Available Studies on ligand binding potential of glycyrrhizic acid, a potential agonist to PPARγ, displayed encouraging results in amelioration of metabolic syndrome. The regulation of gene cassettes by PPARγ affects glucose homeostasis, lipid, lipoprotein metabolism and adipogenesis. This study was performed to determine the effects of GA on total PPARγ and LPL expression levels, lipid parameters and HOMA-IR. Oral administration of 100 mg/kg GA for 24 hours resulted in an increase in insulin sensitivity with decreases in blood glucose, serum insulin and HOMA-IR. Improvement in serum lipid parameters was also observed with a decrease in triacylglycerol, total cholesterol and LDL-cholesterol and an elevation in HDL-cholesterol. GA administration also resulted in up-regulation of total PPARγ and LPL expression levels in the visceral and subcutaneous adipose tissues, abdominal and quadriceps femoris muscles, as well as liver and kidney, with a significant up-regulation only in the visceral adipose tissue, abdominal and quadriceps femoris muscles. Thus, oral administration of 100 mg/kg GA for 24 hours improved insulin sensitivity and lipid profiles and induced upregulation of total PPARγ and LPL expression levels in all studied tissues.

  7. Leptin Regulation of Mammary Cell Growth

    National Research Council Canada - National Science Library

    Pighetti, Gina

    2000-01-01

    .... The studies of this proposal were designed to test the hypothesis that the interaction of leptin with its receptor regulates normal and pathologic mammary epithelial cell proliferation and/or differentiation...

  8. Benefits of leptin therapy in HIV patients

    Directory of Open Access Journals (Sweden)

    Uma Sinha

    2012-01-01

    Full Text Available Leptin therapy in human recombinant form has recently been used in HIV-associated lipodystrophy syndrome on experimental basis in some small short-term clinical trials. It has shown its beneficial effects only in hypoleptinemic HIV-infected patients by causing definite improvement in their insulin sensitivity, glucose tolerance, lipid status, and truncal obesity. Leptin prevents lipotoxicity and activates insulin signaling pathways through several postulated mechanisms. Central leptin insufficiency with peripheral hyperleptinemia has come out to be a significant contributor to the development of obesity and metabolic syndrome. In this article, we will review the basis of leptin therapy in HIV patients, with its promises. However, further larger clinical trials are needed to prove its long-term efficacy in the control of metabolic complications related to HIV therapy.

  9. Leptin and cancer: Pathogenesis and modulation

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    Deep Dutta

    2012-01-01

    Full Text Available Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP, systemic inflammation (TNF-α, IL6, angiogenic factors (VEGF and hypoxia inducible factor-1a (HIF-1a expression. In this review, the current understanding of leptin′s role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described.

  10. Pivotal role of leptin in insulin effects

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    R.B. Ceddia

    1998-06-01

    Full Text Available The OB protein, also known as leptin, is secreted by adipose tissue, circulates in the blood, probably bound to a family of binding proteins, and acts on central neural networks regulating ingestive behavior and energy balance. The two forms of leptin receptors (long and short forms have been identified in various peripheral tissues, a fact that makes them possible target sites for a direct action of leptin. It has been shown that the OB protein interferes with insulin secretion from pancreatic islets, reduces insulin-stimulated glucose transport in adipocytes, and increases glucose transport, glycogen synthesis and fatty acid oxidation in skeletal muscle. Under normoglycemic and normoinsulinemic conditions, leptin seems to shift the flux of metabolites from adipose tissue to skeletal muscle. This may function as a peripheral mechanism that helps control body weight and prevents obesity. Data that substantiate this hypothesis are presented in this review.

  11. Physical Activity Modifies the Effect of LPL, LIPC and CETP polymorphisms on HDL-C Levels and the Risk of Myocardial Infarction in Caucasian Women

    Science.gov (United States)

    Ahmad, Tariq; Chasman, Daniel I.; Buring, Julie E.; Lee, I-Min; Ridker, Paul M; Everett, Brendan M.

    2010-01-01

    Background Recent genome-wide association studies have identified common variants associated with high-density lipoprotein cholesterol (HDL-C). Whether these associations are modified by physical activity, which increases HDL-C levels and reduces the risk of cardiovascular disease (CVD), is uncertain. Methods and Results In a prospective cohort study of 22,939 apparently healthy Caucasian US women, we selected 58 single nucleotide polymorphisms (SNPs) in 9 genes that demonstrated genome-wide association (P<5×10−8) with HDL-C levels and sought evidence of effect modification according to levels of physical activity (PA). PA modified the effects on HDL-C of 7 SNPs at 3 loci, and the strongest evidence of effect was observed for rs10096633 at LPL, rs1800588 at LIPC and rs1532624 at CETP (each P-interaction <0.05). The per-minor-allele increase in HDL-C for rs1800588 at LIPC and rs1532624 at CETP was greater in active than inactive women, whereas the reverse was observed for rs10096633 at LPL. Minor-allele carrier status at the LPL SNP was associated with a reduced risk of MI in active (Hazard Ratio [HR] 0.42, 95% Confidence Interval [CI] 0.23–0.76) but not amongst inactive women (HR 1.10, 95% CI 0.83–1.44; P-interaction=0.007). By contrast, carrier status at the CETP SNP was associated with a reduced risk of MI regardless of activity level (HR 0.72, 95% CI 0.57–0.92; P-interaction=0.71). No association between LIPC SNP carrier status and MI risk was noted Conclusions The effects of common variants in the LPL, LIPC and CETP genes on HDL-C levels are modified by PA. For a common variant in LPL, the impact on MI varied by activity level, while the effects of a common variant in CETP on MI risk did not. PMID:21252145

  12. Cinnamon extract attenuates TNF-alpha-induced intestinal lipoprotein ApoB48 overproduction by regulating inflammatory, insulin, and lipoprotein pathways in enterocytes

    Science.gov (United States)

    We evaluated whether a water extract of cinnamon (CE = Cinnulin PF®) attenuates the dyslipidemia induced by TNF-alpha in Triton WR-1339-treated hamsters, and whether CE inhibited the over-secretion of apoB48-induced by TNF-alpha in enterocytes in a 35S-labelling study. In vivo, oral treatment with C...

  13. The expression of apoB mRNA editing factors is not the sole determinant for the induction of editing in differentiating Caco-2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Galloway, Chad A. [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States); Smith, Harold C., E-mail: harold.smith@rochester.edu [Department of Biochemistry and Biophysics, University of Rochester School of Medicine, 601 Elmwood Ave., Rochester, NY 14642 (United States)

    2010-01-01

    Apolipoprotein B mRNA is edited at cytidine 6666 in the enterocytes lining the small intestine of all mammals; converting a CAA codon to a UAA stop codon. The conversion is {approx}80% efficient in this tissue and leads to the expression of the truncated protein, ApoB48, essential for secretion of dietary lipid as chylomicrons. Caco-2 cell raft cultures have been used as an in vitro model for the induction of editing activity during human small intestinal cell differentiation. This induction of apoB mRNA editing has been ascribed to the expression of APOBEC-1. In agreement our data demonstrated differentiation-dependent induction of expression of the editing enzyme APOBEC-1 and in addition we show alternative splicing of the essential auxiliary factor ACF. However, transfection of these editing factors in undifferentiated proliferating Caco-2 cells was not sufficient to induce robust apoB mRNA editing activity. Only differentiation of Caco-2 cells could induce more physiological like levels of apoB mRNA editing. The data suggested that additional regulatory mechanism(s) were induced by differentiation that controlled the functional activity of editing factors.

  14. The importance of leptin in animal science

    Directory of Open Access Journals (Sweden)

    Mirela Ahmadi

    2016-05-01

    Full Text Available There are two different neurons that control the energetic homeostasis in animals: appetite-stimulating and appetite-suppressing neurons. Leptin is a peptide hormone (also known as “satiety hormone”, released by adipose cells, being an anorexigenic compound which inhibit the hunger. Leptin function in animal organism is opposite by the action of ghrelin – a peptide hormone acting as an orexigenic compound that activate the hunger sensation. The quantity of leptin produced in organism is correlated by the size and the number of adipocytes, and of course by the lipid tissue mass. The action of leptin is in accordance with the neuropeptide Y that signaling the brain to increase the appetite and make the animal to eat. When the animals lose weight, the mass of adipose tissue is diminished, that has as consequence a decrease the leptin concentration in the blood. Blood leptin is correlated also with other characteristics, such as: fasting for a short term, stress, physical activity, sleep duration (prehibernation and hibernation, insulin concentration, obesity and diabetes.

  15. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Holst, J J; Møller, Søren

    2000-01-01

    concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied...

  16. Sheep oocyte expresses leptin and functional leptin receptor mRNA

    Directory of Open Access Journals (Sweden)

    Seyyed Jalil Taheri

    2016-09-01

    Conclusions: The result of present study reveals that leptin and its functional receptor (Ob-Rb mRNA are expressed in sheep oocyte and further studies should investigate the role(s of leptin on sheep oocyte physiology and embryo development.

  17. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats

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    Yingli Lu

    2016-11-01

    Full Text Available Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n=10 each: control, sedentary hypoxic living for 1 to 4 weeks (SH1, SH2, SH3, and SH4, living and exercise training in normoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4, and living and exercise training in hypoxic conditions for 1 to 4 weeks (TN1, TN2, TN3, and TN4. Epididymal adipose tissue expression levels of leptin and leptin receptor were determined. Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P<0.05 to P<0.01, and higher expression of leptin and leptin receptor (P<0.05 to P<0.01 in adipose tissue. Conclusion: In a rodent model of altitude training, living and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  18. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Holst, J J; Møller, Søren

    2000-01-01

    Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating lepti...

  19. Elevated circulating leptin levels in arterial hypertension: relationship to arteriovenous overflow and extraction of leptin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Holst, J J; Moller, S

    2000-01-01

    during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng....../l in the controls; Pblood pressure (r=0.38-0.62, P...

  20. Leptin promoter variant G2548A is associated with serum leptin and ...

    Indian Academy of Sciences (India)

    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 ...

  1. Role of leptin in reverse epidemiology in chronic kidney disease

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Tepel, Martin

    2007-01-01

    , indicating leptin resistance. In healthy subjects increased leptin concentration constitutes a biomarker for increased cardiovascular risk. On the other hand, a recent prospective long-term study in patients with chronic kidney disease stage 5 on hemodialysis therapy showed that reduced serum leptin......Leptin is mainly produced by adipocytes and metabolized in the kidney. Leptin is taken up into the central nervous system by a saturable transport system, and controls appetite in rodents and in healthy subjects. Leptin acts on peripheral tissue and increases the inflammatory response...

  2. Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.

    Science.gov (United States)

    Zeman, Miroslav; Jirak, Roman; Jachymova, Marie; Vecka, Marek; Tvrzicka, Eva; Zak, Ales

    2009-01-01

    Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p DM2 or CVD.

  3. Role of leptin in farm animals: a review.

    Science.gov (United States)

    Mácajová, M; Lamosová, D; Zeman, M

    2004-05-01

    The discovery of hormone leptin has led to better understanding of the energy balance control. In addition to its effects on food intake and energy expenditure, leptin has now been implicated as a mediator of diverse physiological functions. Recently, leptin has been cloned in several domestic species. The sequence similarity suggests a common function or mechanism of this peptide hormone across species. Leptin receptors are expressed in most of tissues, which is consistent with the multiplicity of leptin functions. The main goal of this review was to summarize knowledge about effect of leptin on physiology of farm animals. Experiments point to a stimulatory action of leptin on growth hormone (GH) secretion, normal growth and development of the brain. Surprisingly, leptin is synthesized at a high rate in placenta and may function as a growth factor for fetus, signalling the nutritional status from the mother to her offspring. Maturation of reproductive system can be stimulated by leptin administration. Morphological and hormonal changes, consistent with a major role of leptin in the reproductive system, have also been described, including the stimulation of the release of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Leptin has a substantial effect on food intake and feeding behaviour in animals. Administration of leptin reduces food intake. Its level decrease within hours after initiation of fasting. Leptin also serves as a mediator of the adaptation to fasting, and this role may be the primary function for which was the molecule evolved.

  4. Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

    Directory of Open Access Journals (Sweden)

    Bruno A

    2011-05-01

    Full Text Available Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.Methods: We measured the levels of leptin, tumor necrosis factor alpha (TNF-a and soluble form of intercellular adhesion molecule-1 (sICAM-1 in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.Results: In plasma of COPD patients, leptin was inversely correlated with TNF-a and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-a. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-a were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.Conclusion: Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin

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

    Science.gov (United States)

    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

  6. Discovery of the elusive leptin in birds: identification of several 'missing links' in the evolution of leptin and its receptor.

    Directory of Open Access Journals (Sweden)

    Jeremy W Prokop

    Full Text Available Leptin is a pleiotropic protein best known for regulation of appetite and fat storage in mammals. While many leptin orthologs have been identified among vertebrates, an authentic leptin in birds has remained elusive and controversial. Here we identify leptin sequence from the Peregrine falcon, Falco peregrinus (pfleptin, and identify sequences from two other birds (mallard and zebra finch, and 'missing' vertebrates (elephant shark, alligator, Indian python, Chinese soft-shelled turtle, and coelacanth. The pattern of genes surrounding leptin (snd1, rbm28 is syntenic between the falcon and mammalian genomes. Phylogenetic analysis of all known leptin protein sequences improves our understanding of leptin's evolution. Structural modeling of leptin orthologs highlights a highly conserved hydrophobic core in the four-helix cytokine packing domain. A docked model of leptin with the leptin receptor for Peregrine falcon reveals several conserved amino acids important for the interaction and possible coevolution of leptin with its receptor. We also show for the first time, an authentic avian leptin sequence that activates the JAK-STAT signaling pathway. These newly identified sequences, structures, and tools for avian leptin and its receptor will allow elucidation of the function of these proteins in feral and domestic birds.

  7. The role of leptin in the respiratory system: an overview

    Directory of Open Access Journals (Sweden)

    Gourgoulianis Konstantinos I

    2010-10-01

    Full Text Available Abstract Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system.

  8. The role of leptin in the respiratory system: an overview.

    Science.gov (United States)

    Malli, Foteini; Papaioannou, Andriana I; Gourgoulianis, Konstantinos I; Daniil, Zoe

    2010-10-31

    Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have proposed an important role for leptin in lung maturation and development. Studies further suggest a significant impact of leptin on specific respiratory diseases, including obstructive sleep apnoea-hypopnoea syndrome, asthma, COPD and lung cancer. However, as new investigations are under way, the picture is becoming more complex. The scope of this review is to decode the existing data concerning the actions of leptin in the lung and provide a detailed description of leptin's involvement in the most common disorders of the respiratory system.

  9. Role of leptin during childhood growth and development.

    Science.gov (United States)

    Roemmich, J N; Rogol, A D

    1999-12-01

    Leptin, the product of the ob/ob gene in rodents, regulates energy balance and fertility. Two genetic models, the ob/ob mouse (deletion of leptin protein) and the db/db mouse (deletion of leptin receptor) have markedly augmented research in obesity. Human obesity is more closely linked to leptin resistance than to the absence of leptin. Serum leptin concentrations reflect the size of the subcutaneous fat depot better than total fat mass or abdominal visceral fat. At the initiation of puberty there is a divergence in circulating leptin concentrations between boys and girls. In boys, leptin concentrations increase and then markedly decrease to prepubertal concentration levels. In girls there are only increasing concentrations. The authors believe these patterns are relevant to the markedly different alterations in the regional distribution of body fat that occurs in boys and girls at puberty.

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

    Science.gov (United States)

    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

  11. Effect of Pitavastatin Treatment on ApoB-48 and Lp-PLA in Patients with Metabolic Syndrome: Substudy of PROspective Comparative Clinical Study Evaluating the Efficacy and Safety of PITavastatin in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Hyo-Sun Lee

    2016-03-01

    Full Text Available BackgroundApolipoprotein (Apo B-48 is an intestinally derived lipoprotein that is expected to be a marker for cardiovascular disease (CVD. Lipoprotein-associated phospholipase A2 (Lp-PLA2 is a vascular-specific inflammatory marker and important risk predictor of CVD. The aim of this study was to explore the effect of pitavastatin treatment and life style modification (LSM on ApoB-48 and Lp-PLA2 levels in metabolic syndrome (MS patients at relatively low risk for CVD, as a sub-analysis of a previous multi-center prospective study.MethodsWe enrolled 75 patients with MS from the PROPIT study and randomized them into two treatment groups: 2 mg pitavastatin daily+intensive LSM or intensive LSM only. We measured the change of lipid profiles, ApoB-48 and Lp-PLA2 for 48 weeks.ResultsTotal cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and ApoB-100/A1 ratio were significantly improved in the pitavastatin+LSM group compared to the LSM only group (P≤0.001. Pitavastatin+LSM did not change the level of ApoB-48 in subjects overall, but the level of ApoB-48 was significantly lower in the higher mean baseline value group of ApoB-48. The change in Lp-PLA2 was not significant after intervention in either group after treatment with pitavastatin for 1 year.ConclusionPitavastatin treatment and LSM significantly improved lipid profiles, ApoB-100/A1 ratio, and reduced ApoB-48 levels in the higher mean baseline value group of ApoB-48, but did not significantly alter the Lp-PLA2 levels.

  12. Effect of Pitavastatin Treatment on ApoB-48 and Lp-PLA₂ in Patients with Metabolic Syndrome: Substudy of PROspective Comparative Clinical Study Evaluating the Efficacy and Safety of PITavastatin in Patients with Metabolic Syndrome.

    Science.gov (United States)

    Lee, Hyo Sun; Jung, Chang Hee; Kim, Sung Rae; Jang, Hak Chul; Park, Cheol Young

    2016-03-01

    Apolipoprotein (Apo) B-48 is an intestinally derived lipoprotein that is expected to be a marker for cardiovascular disease (CVD). Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a vascular-specific inflammatory marker and important risk predictor of CVD. The aim of this study was to explore the effect of pitavastatin treatment and life style modification (LSM) on ApoB-48 and Lp-PLA₂ levels in metabolic syndrome (MS) patients at relatively low risk for CVD, as a sub-analysis of a previous multi-center prospective study. We enrolled 75 patients with MS from the PROPIT study and randomized them into two treatment groups: 2 mg pitavastatin daily+intensive LSM or intensive LSM only. We measured the change of lipid profiles, ApoB-48 and Lp-PLA₂ for 48 weeks. Total cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and ApoB-100/A1 ratio were significantly improved in the pitavastatin+LSM group compared to the LSM only group (P≤0.001). Pitavastatin+LSM did not change the level of ApoB-48 in subjects overall, but the level of ApoB-48 was significantly lower in the higher mean baseline value group of ApoB-48. The change in Lp-PLA₂ was not significant after intervention in either group after treatment with pitavastatin for 1 year. Pitavastatin treatment and LSM significantly improved lipid profiles, ApoB-100/A1 ratio, and reduced ApoB-48 levels in the higher mean baseline value group of ApoB-48, but did not significantly alter the Lp-PLA₂ levels.

  13. The role of leptin in the respiratory system: an overview

    OpenAIRE

    Malli, Foteini; Papaioannou, Andriana I; Gourgoulianis, Konstantinos I; Daniil, Zoe

    2010-01-01

    Abstract Since its cloning in 1994, leptin has emerged in the literature as a pleiotropic hormone whose actions extend from immune system homeostasis to reproduction and angiogenesis. Recent investigations have identified the lung as a leptin responsive and producing organ, while extensive research has been published concerning the role of leptin in the respiratory system. Animal studies have provided evidence indicating that leptin is a stimulant of ventilation, whereas researchers have prop...

  14. Effect of the 3'APOB-VNTR polymorphism on the lipid profiles in the Guangxi Hei Yi Zhuang and Han populations

    Science.gov (United States)

    Ruixing, Yin; Guangqin, Chen; Yong, Wang; Weixiong, Lin; Dezhai, Yang; Shangling, Pan

    2007-01-01

    Background Apolipoprotein (Apo) B is the major component of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and chylomicrons. Many genetic polymorphisms of the Apo B have been described, associated with variation of lipid levels. However, very few studies have evaluated the effect of the variable number of tandem repeats region 3' of the Apo B gene (3'APOB-VNTR) polymorphism on the lipid profiles in the special minority subgroups in China. Thus, the present study was undertaken to study the effect of the 3'APOB-VNTR polymorphism on the serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. Methods A total of 548 people of Hei Yi Zhuang were surveyed by a stratified randomized cluster sampling. The epidemiological survey was performed using internationally standardized methods. Serum lipid and apolipoprotein levels were measured. The 3'APOB-VNTR alleles were determined by polymerase chain reaction (PCR) followed by electrophoresis in polyacrylamide gels, and classified according to the number of repeats of a 15-bp hypervariable elements (HVE). The sequence of the most common allele was determined using the PCR and direct sequencing. The possible association between alleles of the 3'APOB-VNTR and lipid variables was examined. The results were compared with those in 496 people of Han who also live in that district. Results Nineteen alleles ranging from 24 to 64 repeats were detected in both Hei Yi Zhuang and Han. HVE56 and HVE58 were not be detected in Hei Yi Zhuang whereas HVE48 and HVE62 were totally absent in Han. The frequencies of HVE26, HVE30, HVE46, heterozygote, and short alleles (VNTR-LS (carrier of one long and one short alleles) than in VNTR-LL (the individual carrying two long alleles) genotypes. The levels of TC, triglycerides (TG), LDL cholesterol, and Apo B in Hei Yi Zhuang were higher in both HVE34 and HVE36 alleles than in HVE32 allele. The levels of TC, TG, HDL-C and Apo B in Hei Yi Zhuang were also higher in

  15. Leptin responses to bovine interferon- α and insulin in cattle

    African Journals Online (AJOL)

    Leptin is a protein synthesized and secreted mainly by adipose tissue. Peripheral administration of different inflammatory cytokines increases both leptin protein and mRNA expression in rodents. We previously showed that injection of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF-α) did not affect leptin ...

  16. Correlation between maternal and cord blood leptin and fetal growth

    African Journals Online (AJOL)

    SERVER

    2007-09-05

    Sep 5, 2007 ... IL -2 and growth hormone. The long form of the leptin receptor functions similarly to cytokine ... regulation of leptin synthesis and the risk for obesity in the offspring. In species such as the human and sheep, ..... Hormonal regulation of leptin levels in the fetus and neonate might be different from the endocrine ...

  17. Influence of age on leptin induced skeletal muscle signaling

    DEFF Research Database (Denmark)

    Guadalupe Grau, Amelia; Larsen, Steen; Guerra, Borja

    2014-01-01

    Age associated fat mass accumulation could be due to dysregulation of leptin signaling in skeletal muscle. Thus, we investigated total protein expression and phosphorylation levels of the long isoform of the leptin receptor (OB-Rb), and leptin signaling through Janus Kinase 2 (JAK2)/signal...... skeletal muscle of different age....

  18. Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate ...

    African Journals Online (AJOL)

    Purpose: To investigate the protective effects of plumbagin against liver fibrosis and explore the influence of plumbagin on the proliferation of hepatic stellate cells (HSCs). Methods: HSC-LX2 cells were divided into blank/control group, 100 ng/ml leptin group, 100 ng/ml leptin + 2 μmol/L plumbagin group, 100 ng/ml leptin + ...

  19. Gender differences in leptin levels and physiology: a role for leptin in human reproduction.

    Science.gov (United States)

    Wauters, M; Van Gaal, L

    1999-01-01

    Leptin, an adipocyte-derived hormone known to play an important role in body-weight regulation, has been shown to be expressed differentially in men and women. These observations are potentially important for the understanding of differences between men and women in regulation of food intake, weight gain, and body fat distribution. Leptin is also involved in female fertility, especially in pubertal development. It may well be the triggering signal for the onset of puberty in girls. Although the exact mechanisms and interactions with sex steroids are not yet fully established, it is clear that leptin plays a role as an endocrine mediator in sexual development and reproduction.

  20. Leptin levels in free ranging striped mice (Rhabdomys pumilio) increase when food decreases: the ecological leptin hypothesis.

    Science.gov (United States)

    Schradin, Carsten; Raynaud, Julien; Arrivé, Mathilde; Blanc, Stéphane

    2014-09-15

    Leptin is a hormone informing the body about its fat stores, reducing appetite and foraging and as such reducing fattening of individuals. In laboratory rodents, leptin secretion is highly correlated to the amount of adipose tissue. We compared this to the alternative ecological leptin hypothesis, which based on the behavioural effects of leptin predicts that leptin levels are disassociated from adipose tissue when fattening is of evolutionary advantage to survive coming periods of low food availability. Studying a species that has to survive a dry season with low food availability, we tested the ecological leptin hypothesis, predicting low leptin levels when food availability and thus adiposity is high promoting foraging and fattening, but high leptin levels in the seasons of low food availability, reducing energetic costs due to foraging. We measured leptin levels in 154 samples of free living African striped mice (Rhabdomys pumilio). Striped mice gain significant body mass during the moist season to survive the following dry season with low food availability. We found a strong seasonal effect, with higher leptin levels in the dry season with low food availability, which was in contrast to the hypothesis deriving from studies on laboratory rodents, but in agreement with ecological leptin hypothesis: leptin levels remained low in the period of high food availability, allowing fattening, but increased during periods of low food availability, possibly suppressing energetically costly foraging in an environment where foraging success would have been very low. Leptin correlated significantly and negatively with testosterone levels, and high testosterone levels in the moist season could explain why leptin levels were low even though food availability was high. However, analysing samples from an experimental laboratory study where testosterone levels were increased via implants found no support for a suppressive role of testosterone on leptin. In sum, our study

  1. Role of leptin in female reproduction.

    Science.gov (United States)

    Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

    2015-01-01

    Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

  2. Leptin Level in Women with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Alexander V. Dreval, PhD, ScD

    2013-06-01

    Full Text Available A detailed study of the dynamics of leptin in the various types of disturbances in carbohydrate metabolism could reveal its role in the pathogenesis of Type 2 Diabetes Mellitus (T2DM. The aim of this study was to investigate the Fasting Leptin Level (FLL and effect of acute hyperinsulinemia during the Intravenous Glucose Tolerance Test (IVGTT on the leptin levels in women with Insulin Resistance Syndrome (IRS. Materials and Methods: In total, 59 obese women (54.0 [48.5-60.0] yrs; BMI – 33.2 [29.0-37.2] kg/m² with IRS (12 – obesity (NGT, 18 - ITG and 30 - T2DM were observed. The IVGTT test was done only in women with impaired glucose tolerance (IGT and T2DM. The leptin level was investigated during fasting conditions and again 120 min post glucose loading. Then the Hepatic glucose production Index (H-index was calculated using the IVGTT data. Results: The FLL in women with normal glucose tolerance (NGT was almost two times greater than in women with IGT and T2DM. A negative relationship was found to exist between FLL and HbA1c in T2DM (r=0.3, p8%. The leptin level significantly decreased at 120 min of IVGTT in both the IGT and T2DM groups (p<0.05. Conclusion: The FLL depended upon the degree of glucose metabolism impairment; postprandial leptin response to the glucose load was lower in the IGT group than in the T2DM subjects.

  3. Expression and immunohistochemical localization of leptin in human periapical granulomas

    Science.gov (United States)

    Martín-González, Jénifer; Carmona-Fernández, Antonio; Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Sánchez-Margalet, Víctor

    2015-01-01

    Background Leptin, initially described as an adipocyte-derived hormone to regulate weight control, is expressed in normal and inflamed human dental pulp, being up-regulated during pulp experimental inflammation. Leptin receptor (LER) has been identified in human periapical granulomas. The aim of this study was to analyze and characterize the expression of leptin in human periapical granulomas. Material and Methods Fifteen periapical inflammatory lesions were obtained from extracted human teeth and teeth which underwent periapical surgery. After their morphological categorization as periapical granulomas and gradation of the inflammatory infiltrate, they were examined by immunohistochemistry using human leptin policlonal antibodies. Leptin mRNA expression was also determined by quantitative real-time PCR (qRT-PCR) and the amount of leptin protein was analyzed by immunoblot. Results All periapical lesions exhibited the characteristic of chronic granulomatous inflammatory process with inflammatory infiltrate grade III. Leptin+ cells were detected in 13 periapical granulomas (86.6%). The median number of Leptin+ cells in periapical granulomas was 1.70 (0.00-7.4). Amongst the inflammatory cells in the periapical granulomas, only macrophages were reactive to leptin antibodies. Western blot analysis revealed the presence in all samples of a protein with apparent molecular weight of approximately 16 kDa, corresponding to the estimated molecular weights of leptin. The expression of leptin mRNA was confirmed by qRT-PCR analysis and the size of the amplified fragment (296 bp for leptin and 194 bp for cyclophilin) was assessed by agarose gel electrophoresis. Conclusions For the first time, it has been demonstrated that human periapical granuloma expresses the adipokine leptin. Key words: Apical granuloma, dental pulp, endodontics, leptin, leptin receptor, immune system, immunohistochemistry, periapical inflammatory response. PMID:25662559

  4. Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia.

    Science.gov (United States)

    Telles, Mônica Marques; da Silva, Thaís Girão; Watanabe, Regina Lúcia Harumi; de Andrade, Iracema Senna; Estadella, Debora; Nascimento, Cláudia Maria Oller; Oyama, Lila Missae; Ribeiro, Eliane Beraldi

    2013-06-10

    Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated. Male rats received four daily injections of leptin (5 μg) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection. For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 μg) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (-74%) and the epididymal (-99%) depots while no differences were observed in the subcutaneous depot. The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Wedelolactone Regulates Lipid Metabolism and Improves Hepatic Steatosis Partly by AMPK Activation and Up-Regulation of Expression of PPARα/LPL and LDLR.

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    Full Text Available Hyperlipidemia is considered one of the greatest risk factors of cardiovascular diseases. We investigated the anti-hyperlipidemic effect and the underlying mechanism of wedelolactone, a plant-derived coumestan, in HepG2 cells and high-fat diet (HFD-induced hyperlipidemic hamsters. We showed that in cultured HepG2 cells, wedelolactone up-regulated protein levels of adenosine monophosphate activated protein kinase (AMPK and peroxisome proliferator-activated receptor-alpha (PPARα as well as the gene expression of AMPK, PPARα, lipoprotein lipase (LPL, and the low-density lipoprotein receptor (LDLR. Meanwhile, administration of wedelolactone for 4 weeks decreased the lipid profiles of plasma and liver in HFD-induced hyperlipidemic hamsters, including total cholesterol (TC, triglycerides (TG, and low-density lipoprotein-cholesterol (LDL-C. The activation of AMPK and up-regulation of PPARα was also observed with wedelolactone treatment. Furthermore, wedelolactone also increased the activities of superoxidase dismutase (SOD and glutathione peroxidase (GSH-Px and decreased the level of the lipid peroxidation product malondialdehyde (MDA in the liver, therefore decreasing the activity of alanine aminotransferase (ALT. In conclusion, we provide novel experimental evidence that wedelolactone possesses lipid-lowering and steatosis-improving effects, and the underlying mechanism is, at least in part, mediated by the activation of AMPK and the up-regulation of PPARα/LPL and LDLR.

  6. Feeding a High Concentrate Diet Down-Regulates Expression of ACACA, LPL and SCD and Modifies Milk Composition in Lactating Goats.

    Directory of Open Access Journals (Sweden)

    Hui Tao

    Full Text Available High concentrate diets are fed to early and mid-lactation stages dairy ruminants to meet the energy demands for high milk production in modern milk industry. The present study evaluated the effects of a high concentrate diet on milk fat and milk composition, especially, cis-9, trans-11 CLA content in milk and gene expression of lactating goats. Eight mid-lactating goats with rumen fistula were randomly assigned into a high concentrate diet (HCD group and low concentrate diet (LCD group. High concentrate diet feeding significantly increased lipopolysaccharides (LPS in plasma and decreased milk fat content, vaccenic acid (VA and cis-9, trans-11 CLA in milk of the lactating goats. The mRNA expression levels of sterol regulatory element binding protein B 1c (SREBP1c, lipoprotein lipase (LPL, fatty acid synthetase (FASN and acetyl-CoA carboxylase α (ACACA, ACCα involving in lipid metabolism were analyzed, and ACACA and LPL all decreased in their expression level in the mammary glands of goats fed a high concentrate diet. DNA methylation rate of stearoyl-CoA desaturase (SCD was elevated and decreased, and SCD mRNA and protein expression was reduced significantly in the mammary glands of goats fed a high concentrate diet. In conclusion, feeding a high concentrate diet to lactating goats decreases milk fat and reduced expression of SCD in the mammary gland, which finally induced cis-9, trans-11 CLA content in milk.

  7. Duplicated leptin receptors in two species of eel bring new insights into the evolution of the leptin system in vertebrates.

    Directory of Open Access Journals (Sweden)

    Marina Morini

    Full Text Available Since its discovery in mammals as a key-hormone in reproduction and metabolism, leptin has been identified in an increasing number of tetrapods and teleosts. Tetrapods possess only one leptin gene, while most teleosts possess two leptin genes, as a result of the teleost third whole genome duplication event (3R. Leptin acts through a specific receptor (LEPR. In the European and Japanese eels, we identified two leptin genes, and for the first time in vertebrates, two LEPR genes. Synteny analyses indicated that eel LEPRa and LEPRb result from teleost 3R. LEPRb seems to have been lost in the teleost lineage shortly after the elopomorph divergence. Quantitative PCRs revealed a wide distribution of leptins and LEPRs in the European eel, including tissues involved in metabolism and reproduction. Noticeably, leptin1 was expressed in fat tissue, while leptin2 in the liver, reflecting subfunctionalization. Four-month fasting had no impact on the expression of leptins and LEPRs in control European eels. This might be related to the remarkable adaptation of silver eel metabolism to long-term fasting throughout the reproductive oceanic migration. In contrast, sexual maturation induced differential increases in the expression of leptins and LEPRs in the BPG-liver axis. Leptin2 was strikingly upregulated in the liver, the central organ of the reproductive metabolic challenge in teleosts. LEPRs were differentially regulated during sexual maturation, which may have contributed to the conservation of the duplicated LEPRs in this species. This suggests an ancient and positive role of the leptin system in the vertebrate reproductive function. This study brings new insights on the evolutionary history of the leptin system in vertebrates. Among extant vertebrates, the eel represents a unique case of duplicated leptins and leptin receptors as a result of 3R.

  8. Behavioral, hormonal and central serotonin modulating effects of injected leptin.

    Science.gov (United States)

    Haleem, Darakhshan J; Haque, Zeba; Inam, Qurrat-ul-Aen; Ikram, Huma; Haleem, Muhammad Abdul

    2015-12-01

    Leptin is viewed as an important target for developing novel therapeutics for obesity, depression/anxiety and cognitive dysfunctions. The present study therefore concerns behavioral, hormonal and central serotonin modulating effects of systemically injected leptin. Pharmacological doses (100 and 500 μg/kg) of leptin injected systemically decreased 24h cumulative food intake and body weight in freely feeding rats and improved acquisition and retention of memory in Morris water maze test. Potential anxiety reducing, hormonal and serotonin modulating effects of the peptide hormone were determined in a separate experiment. Animals injected with 100 or 500 μg/kg leptin were tested for anxiety in an elevated plus maze test 1h later. A significant increase in the number of entries and time passed in open arm of the elevated plus maze in leptin injected animals suggested pronounced anxiety reducing effect. Moreover, circulating levels of leptin correlated significantly with anxiety reducing effects of the peptide hormone. Serum serotonin increased and ghrelin decreased in leptin injected animals and correlated, positively and negatively respectively, with circulating leptin. Corticosterone increased at low dose and levels were normal at higher dose. Serotonin metabolism in the hypothalamus and hippocampus decreased only at higher dose of leptin. The results support a role of leptin in the treatment of obesity, anxiety and cognitive dysfunctions. It is suggested that hormonal and serotonin modulating effects of leptin can alter treatment efficacy in particularly comorbid conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Relationship Between the Serum Leptin and Children with Malnutrition

    International Nuclear Information System (INIS)

    Xu Jixun

    2010-01-01

    To investigate the relationship between the serum leptin and the children with malnutrition, the serum leptin levels in 50 malnourished children and 50 normal children were determined by RIA. The results showed that the serum leptin levels in children with malnutrition were significantly lower than that in control group (P<0.05). The serum leptin levels in children with malnutrition were positively correlated with body mass index values (r= 0.650, P<0.05), and positively correlated with serum albumin values (r= 0.740,P<0.05). The serum leptin levels in female children were higher than that in men children. The leptin may involve in the regulation of the body nutritional status of children. The serum leptin level may be correlated with the degree of child malnutrition and may be used as a laboratory indicator for the diagnosis of child malnutrition. (authors)

  10. Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk.

    Science.gov (United States)

    Nozhenko, Yuriy; Asnani-Kishnani, Madhu; Rodríguez, Ana M; Palou, Andreu

    2015-01-01

    A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15) in rat dams, and the relation with morphometric parameters (dams and pups). Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10) which may be related with pup's growth (males and females) and with the well-known (in the literature) plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation.

  11. Hindbrain leptin receptor stimulation enhances the anorexic response to cholecystokinin.

    Science.gov (United States)

    Williams, Diana L; Baskin, Denis G; Schwartz, Michael W

    2009-11-01

    Leptin is thought to reduce food intake, in part, by increasing sensitivity to satiation signals, including CCK. Leptin action in both forebrain and hindbrain reduces food intake, and forebrain leptin action augments both the anorexic and neuronal activation responses to CCK. Here, we asked whether leptin signaling in hindbrain also enhances these responses to CCK. We found that food intake was strongly inhibited at 30 min after a combination of 4th-intracerebroventricular (4th-icv) leptin injection and intraperitoneal CCK administration, whereas neither hormone affected intake during this period when given alone. Leptin injections targeted directly at the dorsal vagal complex (DVC) similarly enhanced the anorexic response to intraperitoneal CCK. Intra-DVC leptin injection also robustly increased the number of neurons positive for phospho-STAT3 staining in the area surrounding the site of injection, confirming local leptin receptor activation. Conversely, the anorexic response to 4th-icv leptin was completely blocked by IP devazepide, a CCKA-R antagonist, suggesting that hindbrain leptin reduces intake via a mechanism requiring endogenous CCK signaling. We then asked whether hindbrain leptin treatment enhances the dorsomedial hindbrain, hypothalamus, or amygdala c-Fos responses to IP CCK. We found that, in contrast to the effects of forebrain leptin administration, 4th-icv leptin injection had no effect on CCK-induced c-Fos in any structures examined. We conclude that leptin signaling in either forebrain or hindbrain areas can enhance the response to satiation signals and that multiple distinct neural circuits likely contribute to this interaction.

  12. Dietary components in the development of leptin resistance.

    Science.gov (United States)

    Vasselli, Joseph R; Scarpace, Philip J; Harris, Ruth B S; Banks, William A

    2013-03-01

    Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet. This finding has opened the possibility that specific macronutrients may be capable of inducing leptin resistance, independently of the amount of body fat or circulating leptin present in the treated animals. This review describes several lines of research that have recently emerged indicating that specific types of dietary sugars and fats are capable of inducing leptin resistance in experimental rodent models. The results further show that diet-induced leptin resistance is capable of increasing energy intake and elevating body weight gain under appropriate dietary challenges. It appears that biological mechanisms on multiple levels may underlie the dietary induction of leptin resistance, including alterations in the leptin blood-to-brain transport system, in peripheral glucose metabolism, and in central leptin receptor signaling pathways. What is clear from the findings reviewed here is that diet-induced leptin resistance can occur in the absence of elevated circulating leptin levels and body weight, rendering it a potential cause and/or predisposing factor to excess body weight gain and obesity.

  13. Dietary Components in the Development of Leptin Resistance123

    Science.gov (United States)

    Vasselli, Joseph R.; Scarpace, Philip J.; Harris, Ruth B. S.; Banks, William A.

    2013-01-01

    Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet. This finding has opened the possibility that specific macronutrients may be capable of inducing leptin resistance, independently of the amount of body fat or circulating leptin present in the treated animals. This review describes several lines of research that have recently emerged indicating that specific types of dietary sugars and fats are capable of inducing leptin resistance in experimental rodent models. The results further show that diet-induced leptin resistance is capable of increasing energy intake and elevating body weight gain under appropriate dietary challenges. It appears that biological mechanisms on multiple levels may underlie the dietary induction of leptin resistance, including alterations in the leptin blood-to-brain transport system, in peripheral glucose metabolism, and in central leptin receptor signaling pathways. What is clear from the findings reviewed here is that diet-induced leptin resistance can occur in the absence of elevated circulating leptin levels and body weight, rendering it a potential cause and/or predisposing factor to excess body weight gain and obesity. PMID:23493533

  14. Impact of Novel LDL-C Assessment on the Utility of Secondary Non-HDL-C and ApoB Targets in Selected Worldwide Dyslipidemia Guidelines.

    Science.gov (United States)

    Sathiyakumar, Vasanth; Park, Jihwan; Quispe, Renato; Elshazly, Mohamed B; Michos, Erin D; Banach, Maciej; Toth, Peter P; Whelton, Seamus P; Blumenthal, Roger S; Jones, Steven R; Martin, Seth S

    2018-03-05

    Background -Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). We examined, after considering two LDL-C estimates that differ in accuracy: (1) how frequently non-HDL-C guideline targets could change management; and (2) utility of apoB targets after meeting LDL-C and non-HDL-C targets. Methods -We analyzed 2,518 adults representative of the U.S. population from the 2011-2012 National Health and Nutrition Examination Survey and 126,092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features including coronary disease, diabetes, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-CC F ) and a novel, more accurate method (LDL-C N ). Next, we examined those not meeting non-HDL-C (C and non-HDL-C targets (CC F C≥100 mg/dL, and 7-8% had apoB≥80 mg/dL. Among those with LDL-C F C≥130 mg/dL and 2-3% had apoB≥100 mg/dL. In comparison, among those with LDL-C N C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ~0-3% of individuals with LDL-C N C≥100 mg/dL or apoB≥80 mg/dL compared to 13-38% and 9-25%, respectively, in those with LDL-C F C F or LDL-C N CC F or LDL-C N CC, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets. Clinical Trial Registration -URL: https://clinicaltrials.gov Unique Identifier: NCT01698489.

  15. Subjects with molecularly defined familial hypercholesterolemia or familial defective apoB-100 are not being adequately treated.

    Directory of Open Access Journals (Sweden)

    Trond P Leren

    2011-02-01

    Full Text Available To study whether subjects with a molecular genetic diagnosis of familial hypercholesterolemia (FH or familial defective apoB-100 (FDB are being adequately treated.A questionnaire regarding medical history was sent to 2611 subjects who had been provided with a molecular genetic diagnosis of FH or FDB, and a blood sample was obtained for lipid measurements.956 (36.6% of the 2611 subjects participated. The mean age for starting lipid-lowering therapy was 33.4 (±12.1 years. Among those below 18 years of age, only 20.4% were on lipid-lowering drugs, whereas 89.1% of those aged 18 and above were on lipid-lowering drugs. The mean levels of total serum cholesterol and LDL-cholesterol were 5.7 (±1.5 mmol/l and 3.9 (±1.3 mmol/l, respectively. Among those who were on lipid-lowering drugs, 29.0% and 12.2% had levels of LDL cholesterol below 3.0 mmol/l and 2.6 mmol/l, respectively. Only 47.3% of the 956 subjects were considered as being adequately treated largely due to a failure to titrate their drug regimens. From the use of cholesterol-years score, lipid-lowering therapy must start before the age of 20 in order to prevent the subjects from contracting premature coronary heart disease.The majority of FH/FDB subjects are being diagnosed late in life and are not being adequately treated. In order to prevent them from contracting premature coronary heart disease, it is key that levels of LDL cholesterol are normalized from a young age and that sufficient doses of lipid-lowering drugs are being used.

  16. Kinetics of leptin binding to the Q223R leptin receptor.

    Directory of Open Access Journals (Sweden)

    Hans Verkerke

    Full Text Available Studies in human populations and mouse models of disease have linked the common leptin receptor Q223R mutation to obesity, multiple forms of cancer, adverse drug reactions, and susceptibility to enteric and respiratory infections. Contradictory results cast doubt on the phenotypic consequences of this variant. We set out to determine whether the Q223R substitution affects leptin binding kinetics using surface plasmon resonance (SPR, a technique that allows sensitive real-time monitoring of protein-protein interactions. We measured the binding and dissociation rate constants for leptin to the extracellular domain of WT and Q223R murine leptin receptors expressed as Fc-fusion proteins and found that the mutant receptor does not significantly differ in kinetics of leptin binding from the WT leptin receptor. (WT: ka 1.76×106±0.193×106 M-1 s-1, kd 1.21×10-4±0.707×10-4 s-1, KD 6.47×10-11±3.30×10-11 M; Q223R: ka 1.75×106±0.0245×106 M-1 s-1, kd 1.47×10-4±0.0505×10-4 s-1, KD 8.43×10-11±0.407×10-11 M. Our results support earlier findings that differences in affinity and kinetics of leptin binding are unlikely to explain mechanistically the phenotypes that have been linked to this common genetic variant. Future studies will seek to elucidate the mechanism by which this mutation influences susceptibility to metabolic, infectious, and malignant pathologies.

  17. Hyperleptinemia is required for the development of leptin resistance.

    Directory of Open Access Journals (Sweden)

    Zachary A Knight

    2010-06-01

    Full Text Available Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones.

  18. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

    Energy Technology Data Exchange (ETDEWEB)

    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  19. Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer.

    Science.gov (United States)

    Carroll, Paul A; Healy, Laura; Lysaght, Joanne; Boyle, Terry; Reynolds, John V; Kennedy, M John; Pidgeon, Graham; Connolly, Elizabeth M

    2011-08-01

    Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS compared to obese only or normal weight cancer patients (P < 0.005). There was no difference in intratumoral leptin adiponectin or its ligand receptors in the same groups. Individual features of MetS correlated with Ob and ObR expression, but not obesity markers (BMI, waist circumference). mRNA expression of leptin (Ob) and ObR, in adipose tissue and matched tumor samples, respectively, appear to be associated with obesity status in breast cancer. Increasing insulin resistance is a predominant feature of this higher Ob/ObR expression observed. These novel data indicate that the MetS may be an amenable risk factor for breast cancer. Copyright © 2011 Wiley-Liss, Inc.

  20. Distinct roles of free leptin, bound leptin and soluble leptin receptor during the metabolic-inflammatory response in patients with liver cirrhosis

    NARCIS (Netherlands)

    Ockenga, J.; Tietge, U. J. F.; Boeker, K. H. W.; Manns, M. P.; Brabant, G.; Bahr, M. J.

    2007-01-01

    Background Alteration of the leptin system appears to play a role in the inflammatory-metabolic response in catabolic diseases such as chronic liver diseases. Aim To investigate the association between leptin components, inflammatory markers and hepatic energy and substrate metabolism. Methods We

  1. [The importance of leptin in oncology--hypothesis or facts?].

    Science.gov (United States)

    Gaja, A; Churý, Z

    2001-04-01

    Leptin was described as a protein produced mostly by adipocytes which participates in regulation of caloric intake. This protein has further many physiological regulatory functions especially in hematopoesis and reproduction. The role of leptin in diseases is also considered. Maybe leptin is a part of the pathogenic mechanism or its metabolism can be influenced secondary to disease. Malignant tumours are the important area where leptin can acts. This imagination is supported by recent in vitro studies and some clinical observations. It is consider that some parameters of leptin metabolism can serve as usable marker for diagnosis and monitoring of some malignant tumours--especially breast cancer or some types of leukemia. The authors give a review of actual information of leptin metabolism changes in oncological diseases.

  2. Serum leptin levels in female patients with niddm

    International Nuclear Information System (INIS)

    Haque, Z.; Rahman, M.A.

    2003-01-01

    Objective: To compare serum leptin levels of diabetic and non-diabetic female subjects and also assess the relationship of hyperglycemia with serum insulin, C-peptide and leptin levels. Results: Serum leptin levels of obese diabetic and non-diabetic subjects were significantly higher as compared with lean diabetic patients and non-diabetic subjects (P<0.05). Leptin levels were positively correlated with serum insulin and C-peptide levels. Serum leptin increased with increase in body mass index and waist hip ratio was strongly related with insulin resistance in NIDDM. Conclusion: Leptin levels are increased in obesity and may play a role in development of insulin resistance and NIDDM. (author)

  3. Structure of Leptin Receptor Related with Obesity

    DEFF Research Database (Denmark)

    Toleikis, Zigmantas

    of the receptor, while the D5 domain is the central leptin-binding domain, implicated in the first steps of activation. Both domains are characterized by a fibronectin type III fold and both contain a conserved WSXWS motif (X represents an unconserved amino acid residue), a distinct feature of the cytokine...... receptors. This motif is thought to play a major role in correct folding and activation of the receptor. The complex between leptin and the D5CA domain was analyzed using nuclear magnetic resonance spectroscopy and the amino acid residues implicated in the binding were determined. To investigate which parts...... interactions between the aromatic residues of the peptide. It may be speculated that these differences affect the ability of the full domains to form alternative structures around the WSXWS motif....

  4. Obesity-Related Hypertension: Focus on Leptin

    DEFF Research Database (Denmark)

    Asferg, Camilla Lundegaard

    Background: Hypertension is a leading cause of death worldwide. Population studies have shown that at least two-thirds of hypertension incidence can be attributed directly to overweight and obesity. The underlying mechanisms linking obesity to hypertension are not clear. Various factors have been...... suggested to play a role in obesity-related hypertension such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, inflammation, insulin resistance, physical inactivity, and abnormal production of adipocytokines. Of all adipocytokines, leptin and adiponectin have received most...... attention and both hormones are considered as candidate intermediaries between adipose tissue and overweight and obesity-related disorders. Objectives: To study obesity-related hypertension with special focus on the hormone leptin. As obesity-related hypertension is multifactorial, other biological systems...

  5. Leptin, cortisol and distinct concurrent training sequences.

    Science.gov (United States)

    Rosa, G; Dantas, E; Biehl, C; de Castro e Silva, H; Montano, M A E; de Mello, D B

    2012-03-01

    In order to investigate the effects of distinct concurrent training sequences on serum leptin and cortisol levels, 10 subjects (27.1±4.8 years, body mass index 25.38±0.09) were submitted to a control session, concurrent training 1 and concurrent training 2. Samples of leptin and cortisol were collected. Concurrent training 1 consisted of indoor cycling followed by strength training and concurrent training 2 of strength training followed by indoor cycling. No exercises were performed at the control session. Blood was collected once again to verify the same variables. Shapiro-Wilk, 2-way ANOVA and Tukey post-hoc tests were used. There was a reduction in leptin levels after concurrent training 1 (Δ%= - 16.04; p=0.05) and concurrent training 2 (Δ%= - 8.54; p=0.02). Cortisol decreased after concurrent training 1 (Δ%= - 26.32; p=0.02) and concurrent training 2 (Δ%= - 33.57; p=0.05). There was a high and significant correlation between blood variables only in CS (lep PRE X cort PRE and cort POST: r= - 0.80 and r= - 0.81; lep POST X cort PRE and cort POST: r= - 0.62 and r= - 0.62). Concurrent training promoted a reduction in leptin and cortisol levels irrespective of sequence. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Renaissance of leptin for obesity therapy

    DEFF Research Database (Denmark)

    Quarta, Carmelo; Sánchez-Garrido, Miguel A; Tschöp, Matthias H

    2016-01-01

    leptin coming back?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Thomas Meek and Gregory Morton, DOI: 10.1007/s00125-016-3898-3 , and by Gerald Shulman and colleagues, DOI: 10.1007/s00125-016-3909-4 ) and an overview...... by the Session Chair, Ulf Smith (DOI: 10.1007/s00125-016-3894-7 )....

  7. Leptin and its cardiovascular effects: Focus on angiogenesis

    Directory of Open Access Journals (Sweden)

    Zoya Tahergorabi

    2015-01-01

    Full Text Available Leptin is an endocrine hormone synthesized by adipocytes. It plays a key role in the energy homeostasis in central and peripheral tissues and has additional roles are attributed to it, such as the regulation of reproduction, immune function, bone homeostasis, and angiogenesis. The plasma concentration of leptin significantly increases in obese individuals. In the present review, we give an introduction concerning leptin, its receptors, signaling pathways, and its effect on cardiovascular system, especially on angiogenesis.

  8. [Leptin and the feedback regulation of body weight].

    Science.gov (United States)

    Wang, X; Ye, G; Sun, J

    1999-09-30

    Body weight may be controlled by a negative feedback loop. Recent studies have identified that the ob gene product, leptin, apparently and exclusively expressed in adipose tissue, is a part of the negative feedback loop. Leptin is proposed to act as an afferent signal in the negative feedback loop to hypothalamus that limiting food-intake, controlling energy homeostasis and regulating the mass of adipose tissue. The dificiency of or resistance to leptin causes severe obesity.

  9. Leptin: A Novel Therapeutic Strategy for Alzheimer's Disease

    OpenAIRE

    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. One activity of leptin is the control of AMP-dependent kinase (AMPK). In addition to maintaining lipid levels, AMPK regulates glycogen synthase kinase-3, which modulates tau phosphorylation. Leptin has been shown to reduce the amount of extracellular amyloid-β, both in cell culture and animal models of AD, as well as reduce tau phosphorylation in neuron...

  10. Kadar leptin saliva dan kejadian karies gigi anak obesitas (Salivary leptin levels and caries incidence in obese children

    Directory of Open Access Journals (Sweden)

    Elfrida Atzmaryanni

    2013-09-01

    Full Text Available Background: Children with obesity have a lower incidence of caries. Salivary leptin levels of obese children is higher than normal children. Leptin is protein hormone, contained in saliva. Salivary proteins maintain the balance of the ecosystem in the mouth. Purpose: The article was aimed to study the correlation of salivary leptin levels with caries incidence in obese children. Review: Mouth is reflection of the health status and so many changes occur as a weight gain. Child with obesity has a low incidence of caries than normal. This condition is associated with changes in oral cavity, especially the increase in salivary leptin. Caries is a disease of hard tissues cause by the activty of microorganisms, especially Streptococcus mutans. Salivary proteins maintain the balance of the ecosystem in the mouth. Leptin is a protein saliva, produced predominantly in adipose tissue and conduct active transport to saliva. Salivary leptin works in two ways: as an antimicrobial which prevents the attachment of bacteria on tooth surface or by inducing cytokine that affect the immune system in oral cavity. Conclusion: Salivary leptin is higher in obese children than in normal children. The low incidence of caries on obesity is associated with salivary leptin. Alteration in salivary composition and flow rate also decreased caries in obesity.Latar belakang: Anak yang mengalami obesitas memiliki insiden karies yang rendah. Kadar leptin saliva anak obesitas lebih tinggi dari anak normal. Leptin merupakan salah satu protein hormon yang terdapat di saliva. Protein saliva berfungsi untuk menjaga keseimbangan ekosistem di mulut. Tujuan: Artikel ini bertujuan mempelajari hubungan antara kadar leptin di dalam saliva dengan kejadian karies anak obesitas. Tinjauan pustaka: Rongga mulut merupakan cerminan dari status kesehatan dan banyak perubahan yang terjadi seiring peningkatan berat badan seseorang. Anak Obesitas memiliki insiden karies yang rendah jika dibandingkan

  11. Association between Salivary Leptin Levels and Taste Perception in Children

    Directory of Open Access Journals (Sweden)

    Lénia Rodrigues

    2017-01-01

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

  12. Role of leptin in blood pressure regulation and arterial hypertension.

    Science.gov (United States)

    Bełtowski, Jerzy

    2006-05-01

    Leptin is a 16-kDa protein secreted by white adipose tissue that is primarily involved in the regulation of food intake and energy expenditure. Plasma leptin concentration is proportional to the amount of adipose tissue and is markedly increased in obese individuals. Recent studies suggest that leptin is involved in cardiovascular complications of obesity, including arterial hypertension. Acutely administered leptin has no effect on blood pressure, probably because it concomitantly stimulates the sympathetic nervous system and counteracting depressor mechanisms such as natriuresis and nitric oxide (NO)-dependent vasorelaxation. By contrast, chronic hyperleptinemia increases blood pressure because these acute depressor effects are impaired and/or additional sympathetic nervous system-independent pressor effects appear, such as oxidative stress, NO deficiency, enhanced renal Na reabsorption and overproduction of endothelin. Although the cause-effect relationship between leptin and high blood pressure in humans has not been demonstrated directly, many clinical studies have shown elevated plasma leptin in patients with essential hypertension and a significant positive correlation between leptin and blood pressure independent of body adiposity both in normotensive and in hypertensive individuals. In addition, leptin may contribute to end-organ damage in hypertensive individuals such as left ventricular hypertrophy, retinopathy and nephropathy, independent of regulating blood pressure. Here, current knowledge about the role of leptin in the regulation of blood pressure and in the pathogenesis of arterial hypertension is presented.

  13. [Obesity and leptin association in three Chilean aboriginal populations].

    Science.gov (United States)

    Pérez, F; Santos, J L; Albala, C; Calvillán, M; Carrasco, E

    2000-01-01

    Although there is a clear relationship between body mass index and leptin levels, few authors have addressed the possible influence of ethnic factors on these levels. To measure serum leptin in three different Chilean aboriginal populations. Fasting serum leptin and insulin levels were measured by radioimmunoassay in 345 rural mapuche individuals, 247 rural aymara subjects and 162 urban mapuche subjects. A body mass index of 27.5 kg/m2 was used as cutoff point to classify study subjects. Among the three ethnic groups, women had serum leptin levels three times higher than men. In all three ethnic groups, there was a significant association between leptin levels, body mass index and gender (r2 = 0.32 and 0.5 p mapuche, r2 = 0.32 and 0.5 p mapuche populations). No differences in leptin levels were observed for the interaction between age and insulin. The increments per quartile in leptin levels were lower among mapuche than aymara individuals. Rural mapuche individuals have a high frequency of obesity. However their leptin levels are lower than those of aymara or urban mapuche populations. The higher leptin levels observed in urban mapuche subjects could be due to environmental influences.

  14. Plasma leptin concentration in dogs with diabetes mellitus.

    Science.gov (United States)

    Nishii, Naohito; Yamasaki, Miho; Takasu, Masaki; Honjoh, Tsutomu; Shibata, Haruki; Otsuka, Yoshihiko; Takashima, Satoshi; Ohba, Yasunori; Kitagawa, Hitoshi

    2010-06-01

    The plasma leptin concentration was evaluated in dogs with diabetes mellitus. Twenty normal and sixteen diabetic dogs were divided into nonobese and obese groups based on body condition score, respectively. The obese normal dogs had significantly higher plasma leptin concentrations than the nonobese normal dogs, whereas there was no significant difference between the nonobese and obese diabetic dogs. In addition, the plasma leptin concentration in the obese diabetic dogs was significantly lower than that in the obese normal dogs. In conclusion, the plasma leptin concentrations in the diabetic dogs were affected by factors other than adiposity.

  15. Angiogenic Effect of Leptin in the Quail Chorioallantoic Membrane

    Directory of Open Access Journals (Sweden)

    Pavel Výboh

    2010-01-01

    Full Text Available Leptin, the product of ob gene, beside its key role in the control of body weight and food consumption, can be involved in the control of embryonic development. Leptin administration in ovo accelerated the embryonic and post-embryonic development in Japanese quail. Although the mechanisms of leptin effects on growth and development acceleration are not clear, stimulation of angiogenesis represents one of plausible explanations. Therefore, the aim of the present study was to investigate the pro-angiogenic effect of leptin in vivo in the quail chorioallantoic membrane (CAM. The recombinant murine leptin (10, 100, and 1000 ng was applied either ex ovo on the CAM surface of ex ovo incubated embryos at embryonic day 7 (ED7 or in ovo into the egg albumen at ED5. Changes in blood vessels were quantified by the fractal analysis providing the fractal dimension (Df estimate. Leptin administered in ovo was more efficient in stimulation of angiogenesis than the ex ovo treatment, since 10 ng dose elicited significantly higher (P ex ovo cultivation. Our study confirmed that exogenously applied leptin was able to stimulate angiogenesis in CAM. Leptin-mediated stimulation of angiogenesis may improve nutrient utilization from the yolk and explain at least partially the accelerating effect of leptin on avian embryo growth and development.

  16. Milk Leptin Surge and Biological Rhythms of Leptin and Other Regulatory Proteins in Breastmilk.

    Directory of Open Access Journals (Sweden)

    Yuriy Nozhenko

    Full Text Available A significant number of chronic diseases are linked to perinatal nutrition, and prevention may be associated to naturally occurring components of breast milk. One key hormone in breast milk is leptin, related with the protection from obesity in the adulthood, thus knowing its changes through the day or lactation is crucial. We aimed to investigate the daily rhythms in the milk levels of leptin, together with other two related hormones, ghrelin and adiponectin, during lactation (days 5, 10 and 15 in rat dams, and the relation with morphometric parameters (dams and pups. Summarizing the main results, the existence of biological rhythms, but not daily and maybe circasemidian, was confirmed for the three hormones at the earliest period of lactation. The correlations performed generally showed a possible dependence of milk hormone levels on plasma levels at the early phase of lactation, while with the progression of lactation this dependence may fade and the hormone levels are suggested to be more dependent on mammary gland production/maturation. There was also a correlation between milk leptin and adiponectin levels, especially in the first half of lactation, suggesting a possible parallel regulation. Interestingly, we describe a milk leptin surge around the mid of lactation (at day 10 which may be related with pup's growth (males and females and with the well-known (in the literature plasma leptin surge in pups. All this knowledge may be crucial for future applications in the development of formula milk and in relation with the role of leptin surge during lactation.

  17. A novel LPL intronic variant: g.18704C>A identified by re-sequencing Kuwaiti Arab samples is associated with high-density lipoprotein, very low-density lipoprotein and triglyceride lipid levels

    Science.gov (United States)

    Al-Serri, Ahmad; Annice, Babitha G.; Alnaqeeb, Majed A.; Al-Kandari, Wafa Y.; Dashti, Mohammed

    2018-01-01

    The role interethnic genetic differences play in plasma lipid level variation across populations is a global health concern. Several genes involved in lipid metabolism and transport are strong candidates for the genetic association with lipid level variation especially lipoprotein lipase (LPL). The objective of this study was to re-sequence the full LPL gene in Kuwaiti Arabs, analyse the sequence variation and identify variants that could attribute to variation in plasma lipid levels for further genetic association. Samples (n = 100) of an Arab ethnic group from Kuwait were analysed for sequence variation by Sanger sequencing across the 30 Kb LPL gene and its flanking sequences. A total of 293 variants including 252 single nucleotide polymorphisms (SNPs) and 39 insertions/deletions (InDels) were identified among which 47 variants (32 SNPs and 15 InDels) were novel to Kuwaiti Arabs. This study is the first to report sequence data and analysis of frequencies of variants at the LPL gene locus in an Arab ethnic group with a novel “rare” variant (LPL:g.18704C>A) significantly associated to HDL (B = -0.181; 95% CI (-0.357, -0.006); p = 0.043), TG (B = 0.134; 95% CI (0.004–0.263); p = 0.044) and VLDL (B = 0.131; 95% CI (-0.001–0.263); p = 0.043) levels. Sequence variation in Kuwaiti Arabs was compared to other populations and was found to be similar with regards to the number of SNPs, InDels and distribution of the number of variants across the LPL gene locus and minor allele frequency (MAF). Moreover, comparison of the identified variants and their MAF with other reports provided a list of 46 potential variants across the LPL gene to be considered for future genetic association studies. The findings warrant further investigation into the association of g.18704C>A with lipid levels in other ethnic groups and with clinical manifestations of dyslipidemia. PMID:29438437

  18. Analysis of changes of serum leptin, C-peptide levels and peripheral fat tissue leptin receptor expression in obesity

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Shukui; Fu Lei

    2002-01-01

    Objective: To explore the mechanism of obesity and obesity accompanied type two diabetes mellitus by investigating changes of serum leptin, C-peptide (C-P) levels and leptin receptor expression in peripheral adipose tissues. Methods: Peripheral leptin receptor density was measured via radio-ligand binding method, serum leptin and C - P levels were measured via radioimmunoassay in 91 cases (38 in obesity group, 23 in over weight, and 30 in normal controls). Results: With the increase of body mass index (BMI), the peripheral leptin receptor density of the over weight and obese cases decreased and was mash less than that of normal cases (both p<0.01, respectively). There was no statistical differences for Kd value among the three groups, suggesting no associated change between the binding ability of leptin receptor to its ligand. There was a negative correlation between BMI and leptin receptor density (r = -0.70, p < 0.01). The serum leptin and C-P levels in weight excess and obese subjects with type two DM were both increased, but significantly higher in obese group than those in weight excess group (p < 0.01). The increase of C-P was much marked than that of leptin. Serum C-P level was positively correlated with BMI. Conclusion: Changes of serum leptin, C-P levels and peripheral leptin receptor expression in cases with simple obesity and obesity accompanied with type two DM were related closely with BMI. Type 2 DM in obese subjects was related with leptin resistance and insulin resistance

  19. Leptin and Pathological Indexes in Women with Breast Cancer

    Directory of Open Access Journals (Sweden)

    B Noori Alavicheh

    2015-06-01

    Full Text Available Background & aim: Breast cancer is the most common cancer among women and one of the factors threatening the health of women worldwide. Leptin is a 16 kD glycoprotein hormone produced predominantly by white adipose tissue. Leptin binds to receptors in the hypothalamus and plays a key role in regulation of metabolism. Both leptin and leptin receptor have recently been implicated in processes and progress leading to breast cancer initiation. The aim of this study was to identify if there is association between leptin and pathological indexes in patients with breast cancer Methods: 45women with breast cancer were enrolled. Serum leptin levels of patients were measured by the ELISA method. Pathological information such as stage of the breast cancer, Hormonal receptor (ER, PR and Her2 status in these patients were determined. Result: Results revealed that the patients who were in stage one and two, the mean serum leptin level was (34.18±21.22 ng/ml And patients who were in stage three and four, the mean serum leptin level was (32.21±21/93 ng/ml. Also the mean serum leptin levels in patients whose receptor status of ER, PR and HER2 positive were (35.90±23.55, 35.74±23.91and 37.02±24.25ng/ml, respectively. The Patients whose receptor status of ER, PR and HER2 negative were 26.64±13.13, 28.17±14.26and31.32±19.9ng/ml respectively. No significant association was found between leptin leveland stage of the breast cancer, hormonal receptor (ER, PR and Her2 status in Patients with Breast cancer(p>0.05. Conclusions: In this study, no association was found between serum leptin level and pathological indices in women with Breast cancer in Yasuj, Iran.

  20. Leptin levels in children and adults with classic galactosaemia.

    LENUS (Irish Health Repository)

    Knerr, Ina

    2012-11-07

    Among the long-term complications of Classic Galactosaemia (Gal) is premature ovarian insufficiency (POI) in female patients with subtle abnormalities of reproductive function also reported in male patients. Leptin is a circulating hormone which reflects body energy stores and which affects the neuroendocrine reproductive axis and pubertal development.We measured serum leptin in 28 children (10 girls, 18 boys; mean age 7.6 years, range 0.5-17.9 years) and in 22 adults (10 females, 12 males; mean age 23.9 years, range 18-37 years) with Gal on a strict galactose-restricted diet in comparison with control data.Leptin levels (expressed as SDS for gender and pubertal stage) were lower in Gal children than controls (mean leptin-SDS = -0.71 for girls, p < 0.05, -0.97 for boys compared with SDS = 0 for controls, p < 0.05). In an age-related analysis, leptin levels did not correlate with age in children with Gal for both sexes as it did for matched controls.As expected, females had higher leptin levels than males in either group. In adults with Gal, leptin concentrations were within normal limits for both sexes when adjusted for gender and BMI. There was a linear relationship between log-leptin and BMI in children with Gal and in controls. For Gal women, log-leptin was also associated with BMI. However, for Gal men, and hence for the entire group of adult Gal patients, this association between log-leptin and BMI was not detectable. Our findings suggest that leptin dysregulation may play a role in fertility issues in individuals with Gal from an early age.

  1. Leptin promoter variant G2548A is associated with serum leptin

    Indian Academy of Sciences (India)

    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 ...

  2. Lateral thinking about leptin: a review of leptin action via the lateral hypothalamus.

    Science.gov (United States)

    Leinninger, Gina M

    2011-09-26

    The lateral hypothalamic area (LHA) was initially described as a "feeding center" but we are now beginning to understand that the LHA contributes to other aspects of physiology as well. Indeed, the best-characterized neuronal populations of the LHA (which contain melanin-concentrating hormone (MCH) or the hypocretins/orexins (OX)) are not strictly orexigenic, but also have roles in regulation of the autonomic and sympathetic nervous systems as well as in modulating motivated behavior. Leptin is an anorectic hormone that regulates energy homeostasis and the mesolimbic DA system (which transduces the wanting of food, drugs of abuse, and sex) in part, via actions at the LHA. At least three populations of LHA neurons are regulated by leptin: those containing MCH, OX or the long form of the leptin receptor, LepRb. The emerging picture of leptin interaction with these LHA populations suggests that the LHA is not merely regulating feeding, but is a crucial integrator of energy balance and motivated behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Relation between obesity, lipid profile, leptin and atopic disorders in ...

    African Journals Online (AJOL)

    EL-HAKIM

    count, serum triglycerides and cholesterol, serum leptin (for control group also) and serum total immunoglobulin E (IgE) .... The DSL–10–23100 active Human Leptin ELISA was used. It is an enzymatically amplified 'two .... and the more highly allergenic foods such as eggs, peanuts, tree nuts and fish can be delayed for 2-3.

  4. Hypothalamic leptin action is mediated by histone deacetylase 5

    DEFF Research Database (Denmark)

    Kabra, Dhiraj G; Pfuhlmann, Katrin; García-Cáceres, Cristina

    2016-01-01

    Hypothalamic leptin signalling has a key role in food intake and energy-balance control and is often impaired in obese individuals. Here we identify histone deacetylase 5 (HDAC5) as a regulator of leptin signalling and organismal energy balance. Global HDAC5 KO mice have increased food intake and...

  5. Leptin gene polymorphism in Indian Sahiwal cattle by single strand ...

    African Journals Online (AJOL)

    These leptin gene variants can be sequenced and screened in the entire population to develop single nucleotide polymorphisms (SNPs) for association studies with different productive and reproductive performances and marker assisted selection. Keywords: Leptin gene, PCR-SSCP, genetic variability, dairy cattle

  6. Study of polymorphism of leptin gene receptor in Mazandaran fowls ...

    African Journals Online (AJOL)

    In chickens, leptin is expressed mainly in the liver and adipose tissue. In Iran, Mazandaran native fowls are under recording and breeding programs, but according to the action modes and importance of the leptin receptor, its polymorphisms can be related to economical traits such as body weight. In this study, in order to ...

  7. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    The results showed that leptin could stimulate the proliferation and inhibit the apoptosis of HCT-116 colon cells through the PI3K/Akt/mTOR pathway. Ly294002 (a PI3K inhibitor) and rapamycin (an mTOR inhibitor) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating ...

  8. Lipids and leptin level in natives of Kyrgyzstan.

    Science.gov (United States)

    Mirrakhimov, Erkin; Kerimkulova, Alina; Lunegova, Olga; Mirrakhimov, Aibek; Alibaeva, Nazira; Nabiev, Malik

    2014-04-01

    A possible link between obesity and impaired lipid metabolism is leptin, the 167-amino acid protein, secreted by adipocytes. The content of leptin in the body is closely associated with body mass index (BMI). Data obtained from studies on the association of leptin with dyslipidemia are contradictory. The level of leptin has not been studied in the ethnic Kyrgyz population previously. The purpose of this study was to investigate the relationship between leptin and lipid parameters in a group of ethnic Kyrgyz. The study included 322 ethnic Kyrgyz (145 males, 177 females) aged ≥30 years, living in Kyrgyzstan. Measurement of anthropometric parameters (height, weight, waist circumference [WC], hip circumference [HC]) and blood pressure (BP) was done. Laboratory tests included blood glucose (fasting) in plasma, lipid profile (total cholesterol [TC], triglycerides [TG], high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol), and serum leptin. Leptin was positively correlated with BMI, WC and TG in both sexes and with TC in males. Leptin is associated with BMI, WC and TG in both sexes of Kyrgyz and with TC in Kyrgyz males.

  9. Leptin receptor in peripheral adipose tissues of obese subjects

    International Nuclear Information System (INIS)

    Du Tongxin; Sun Junjiang; Wang Zizheng; Wang Shukui; Fu Lei; Han Liu

    2002-01-01

    Objective: To investigate the relationship between leptin receptor and obesity by studying the leptin receptor density B max and dissociation constant K d in peripheral adipose tissue in subjects with different body weight mass (BMI). Methods: Leptin receptor density B max and K d were assayed via radioligand method in 71 cases, including 32 classified as obese, 19 over-weight and 20 normal control. Results: With the escalating of BMI, the leptin receptor density significantly decreased in obese and over-weight group compared with that in normal control (both P d values were of no differences among all three groups suggesting no correlation between the binding ability of leptin to its receptor and BMI. A negative correlation between BMI and B max (r=-0.76, P<0.01) displayed after all. Conclusion: Leptin receptor density correlates with the BMI in obese cases and it suggests that the down-regulation of leptin receptor may contribute to the occurrence of leptin resistance and obesity after-wards

  10. Role of leptin in the pathogenesis of breast cancer

    Directory of Open Access Journals (Sweden)

    Thayse Fachin Cormanique

    2015-12-01

    Full Text Available Leptin is a small polypeptide codified by the Obese Gene (OB, deeply related with the body fat mass and energetic balance. Due to its diverse biological effects and downstream signal transducers, multiple classifications have been attributed to leptin, as hormone, cytokine, adypokine, growth factor, and developmental factor, among others. This scenario gives us an idea of the size of the potential biological effects generated by this molecule. The concentration of leptin in the body is determined by the amount of adipose tissue; therefore, hyperleptinemia is a common finding in obese individuals. In addition, high levels of circulating leptin may confer a poor prognosis for any pathological condition. Although leptin history has been reported for more than 20 years, its relationship with cancer has gained notoriety in the past ten years, where studies focused on discussing the issue of obesity as a strong risk factor for cancer developing. Further, growing evidences have pointed leptin as a pivotal mediator of immune response, which aggravates the scenario of cancer occurrence in the presence of obesity. Therefore, leptin can present at least two faces in the pathogenesis of breast cancer, acting by immune and non-immune mechanisms. In this paper we review the dynamic of the leptin axis in breast cancer and further discuss its role in disease, immunopathogenesis and prognosis.

  11. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    2016-12-21

    Dec 21, 2016 ... Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 ... increase energy expenditure resulting in body weight loss in rodents (Pelleymounter et ..... response to starvation: implications for the study of wasting disorders. Am. J. Physiol.

  12. Leptin as a Potential Regulator of FGF21

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    2016-03-01

    Full Text Available Background/Aims: Fibroblast growth factor 21 (FGF21, a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.

  13. Adiponectin, leptin and oxidative stress in preeclampsia in Egyptian ...

    African Journals Online (AJOL)

    Adiponectin and Leptin are closely related adipokines that are associated with the oxidative stresses and endothelial dysfunction and proposed to participate in preeclampsia (PE) pathogenesis. This study is to determine changes in serum levels of adiponectin, leptin and oxidative stress in PE women in order to speculate a ...

  14. [CDNA cloning of human leptin and its expression].

    Science.gov (United States)

    Jia, Zhen-Yu; Fu, Xiao-Min; Jin, Ai-Hua; Cao, Jiang

    2003-07-01

    To clone cDNA of human leptin gene and obtain leptin protein for future study on leptin binding proteins. The cDNA of human leptin with 6 x his-tag was cloned by over-hang extension PCR protocol using human genomic DNA as template, and subcloned into in vitro expression vector pIVEX2.3MCS, and the fusion protein was expressed in vitro by Rapid Translation System (RTS) (RTS500 cycle primer Kit and RTS500 ProteoMaster of Roche company). The apparent molecular weight(19.46 kD) and the immuno-specificity of the fusion protein were confirmed by SDS-PAGE and Western blot, and the expressed fusion protein stayed mainly in the supernatant of the reaction mixture in soluble form. This work provides us solid basis for further study on new leptin-associated proteins.

  15. The Role of Leptin in Maintaining Plasma Glucose During Starvation.

    Science.gov (United States)

    Perry, Rachel J; Shulman, Gerald I

    2018-03-01

    For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.

  16. Leptin and ghrelin: Sewing metabolism onto neurodegeneration.

    Science.gov (United States)

    de Candia, Paola; Matarese, Giuseppe

    2017-12-15

    Life expectancy has considerably increased over the last decades. The negative consequence of this augmented longevity has been a dramatic increase of age-related chronic neurodegenerative diseases, such as Alzheimer's, Parkinson's and multiple sclerosis. Epidemiology is telling us there exists a strong correlation between the neuronal loss characterizing these disorders and metabolic dysfunction. This review aims at presenting the evidence supporting the existence of a molecular system linking metabolism with neurodegeneration, with a specific focus on the role of two hormones with a key role in the regulatory cross talk between metabolic imbalance and the damage of nervous system: leptin and ghrelin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Children's psychosocial stress and emotional eating: A role for leptin?

    Science.gov (United States)

    Michels, Nathalie; Sioen, Isabelle; Ruige, Johannes; De Henauw, Stefaan

    2017-05-01

    Psychosocial stress can be a health threat by stimulating unhealthier eating behaviors. We aim to test the role of the hormone leptin in the association between stress and diet/emotional eating as detected in primary school children. In a two-wave longitudinal study with 308 Belgian children (5-12y) in 2010-2012, the association of fasting serum leptin with reported stress (negative events and emotional problems), measured stress by salivary cortisol (overall cortisol output and awakening response), emotional eating and food consumption frequency was examined. Analyses were split by sex. Mediation and moderation by leptin change were tested. One stress marker (overall cortisol output) was significantly correlated with high leptin levels, but only in girls and cross-sectionally. Only in boys, leptin was associated with low emotional eating. Leptin was not a significant predictor of unhealthy food consumption. Leptin change was not a mediator but an enhancing moderator in the link between stress (high cortisol output and emotional problems) and emotional eating in girls: high reports of emotional eating in 2012 were present in the case of combined high 2-year leptin increase and high stress at baseline. Stress (represented by emotional problems and high daily cortisol) seems to lead to hyperleptinemia in girls; and the combination of high stress and hyperleptinemia might make girls more vulnerable to stress-induced eating. No functional data on leptin sensitivity were present, but results might suggest that stress induces lower sensitivity to the anorexigenic leptin activity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:471-480). © 2016 Wiley Periodicals, Inc.

  18. Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.

    Science.gov (United States)

    Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo

    2015-11-01

    Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  19. Leptin and its potential interest in assisted reproduction cycles.

    Science.gov (United States)

    Catteau, A; Caillon, H; Barrière, P; Denis, M G; Masson, D; Fréour, T

    2016-04-01

    Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. The association between depression and leptin is mediated by adiposity.

    Science.gov (United States)

    Morris, Alanna A; Ahmed, Yusuf; Stoyanova, Neli; Hooper, William Craig; De Staerke, Christine; Gibbons, Gary; Quyyumi, Arshed; Vaccarino, Viola

    2012-06-01

    Animal models suggest that impaired leptin production, or leptin resistance despite increased leptin levels, may contribute to depression. The link between leptin and depression could be mediated by obesity, which is more common in depression and increases leptin production. We administered the Beck Depression Inventory-II (BDI-II) to 537 participants (mean [standard deviation (SD)] age = 51 [9] years; female, 61%) enrolled in the Morehouse and Emory Team up to Eliminate Health Disparities (META-Health) study. Leptin levels were examined as continuous log-transformed values. Participants with moderate to severe depression had higher levels of leptin (median [interquartile range] 37.7 [17.6-64.9] ng/mL) than those with mild depression (22.9 [7.0-57.9] ng/mL) or minimal to no depression (19.8 ng/mL [7.8-39.1], p = .003). Participants with moderate to severe depression had higher body mass index (BMI) than those with mild or minimal depression (mean [SD] = 33 [8] versus 31 [9] versus 29 [7] kg/m(2), p = .001). After multivariate adjustment for age, sex, race, smoking status, hypertension, diabetes, blood pressure, lipids, and C-reactive protein, the BDI-II score remained a significant predictor of leptin levels (β = 0.093, p = .01). Further adjustment for BMI eliminated the association between the BDI-II score and leptin (β = 0.03, p = .3). Adjusting for waist circumference in place of BMI revealed similar findings. The association between depression and leptin seems to be mediated by increased adiposity in depressed individuals.

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

    DEFF Research Database (Denmark)

    Fungfuang, Wirasak; Nakada, Tomoaki; Nakao, Nobuhiro

    2013-01-01

    :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......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...... 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...

  2. Two divergent leptin paralogues in zebrafish (Danio rerio) that originate early in teleostean evolution.

    NARCIS (Netherlands)

    Gorissen, M.H.A.G.; Bernier, N.J.; Nabuurs, S.B.; Flik, G.; Huising, M.O.

    2009-01-01

    We describe duplicate leptin genes in zebrafish (Danio rerio) that share merely 24% amino acid identity with each other and only 18% with human leptin. We were also able to retrieve a second leptin gene in medaka (Oryzias latipes). The presence of duplicate leptin genes in these two distantly

  3. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Rattensperger, Dirk; Zidek, Walter

    2007-01-01

    Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy.......Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy....

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

    DEFF Research Database (Denmark)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A

    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...

  5. The association between leptin and depressive symptoms is modulated by abdominal adiposity

    NARCIS (Netherlands)

    Milaneschi, Y.; Sutin, A.R.; Terracciano, A.; Canepa, M.; Gravenstein, K.S.; Egan, J.M.; Vogelzangs, N.; Guralnik, J.M.; Bandinelli, S.; Penninx, B.W.J.H.; Ferrucci, L.

    2014-01-01

    Background: Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can

  6. Mammary gland leptin in relation to lactogenesis in the periparturient dairy goat

    DEFF Research Database (Denmark)

    Rasmussen, Alice Neess; Nielsen, Mette Olaf; Tauson, Anne-Helene

    2008-01-01

    The role of leptin in development of mammary gland secretory function was studied during the periparturient period in dairy goats. Changes in mammary leptin and leptin receptor (short cytoplasmic form) expression were evaluated by real-time RT-PCR and related to changes in milk and plasma leptin...... peak in milk leptin 2 days post-partum needs to be understood. We did not find evidence that milk leptin can be absorbed, and thus play a role in systemic regulation, of the neonatal goat....... concentrations from 5 weeks pre-partum to 7 weeks post-partum. It was further investigated if systemic leptin concentration in the neonate is affected by milk leptin intake. We found no evidence of accumulation of leptin in colostrum pre-partum. Pre- and post-partum milk leptin concentrations were similar...

  7. Leptin effects on the regenerative capacity of human periodontal cells.

    Science.gov (United States)

    Nokhbehsaim, Marjan; Keser, Sema; Nogueira, Andressa Vilas Boas; Jäger, Andreas; Jepsen, Søren; Cirelli, Joni Augusto; Bourauel, Christoph; Eick, Sigrun; Deschner, James

    2014-01-01

    Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFβ1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing.

  8. Leptin Induces an Inflammatory Phenotype in Lean Wistar Rats

    Directory of Open Access Journals (Sweden)

    Monique Allman

    2009-01-01

    Full Text Available The present study addressed the hypothesis that leptin promotes leukocyte trafficking into adipose tissue. Accordingly, male Wistar rats were treated with saline or recombinant rat leptin (1 mg/kg via the tail vein. Leukocyte trafficking in mesenteric venules was quantified by intravital microscopy. Treatment with leptin resulted in a 3- and 5-fold increases in rolling and firm adhesion, respectively. Compared to vehicle controls, leptin enhanced mRNA levels of IL-6 (8-fold and MCP-1 (5-fold in mesenteric adipose tissue (MAT. Similar increases in these markers were observed in mesenteric venules and in liver. Finally, the direct effect of leptin was assessed in C3A hepatocytes treated with leptin for 24 hours (7.8 ng/mL–125 ng/mL. Consistent with observations in vivo, production of ICAM-1, MCP-1, and IL-6 by hepatocytes was increased significantly. These findings support the hypothesis that leptin directly initiates inflammation in the local environment of mesenteric adipose tissue as well as systemically.

  9. Leptin: A Novel Therapeutic Strategy for Alzheimer's Disease

    Science.gov (United States)

    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

    2010-01-01

    Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. One activity of leptin is the control of AMP-dependent kinase (AMPK). In addition to maintaining lipid levels, AMPK regulates glycogen synthase kinase-3, which modulates tau phosphorylation. Leptin has been shown to reduce the amount of extracellular amyloid-β, both in cell culture and animal models of AD, as well as reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models of AD. In humans, weight loss often precedes the onset of dementia in AD and the level of circulating leptin is inversely proportional to the severity of dementia among AD patients. It is speculated that a deficiency in leptin levels or function may contribute to systemic and central nervous system abnormalities leading to AD, suggesting that a leptin replacement therapy may be beneficial for AD. This may be an attractive alternative to the drugs that are currently under development. PMID:19387109

  10. Longitudinal study of leptin levels in chronic hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Averbukh Zhan

    2011-06-01

    Full Text Available Abstract Background The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients. Methods Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters. Results Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2y; p Conclusions Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

  11. Leptin Influence in Craving and Relapse of Alcoholics and Smokers

    Science.gov (United States)

    Aguiar-Nemer, Aline S.; Toffolo, Mayla C. F.; da Silva, Claudio Jeronimo; Laranjeira, Ronaldo; Silva-Fonseca, Vilma A.

    2013-01-01

    Leptin inhibits signaling of dopamine in the nucleus accumbens, suggesting its role in regulating stress and its possible involvement in the neurobiology of reward system. The aim of this study was to review of the literature on the influence of leptin in the craving for alcohol and tobacco and whether there is already evidence that leptin may be a biomarker to indicate risk for craving and relapse. The review used as data bases Medline, LILACS and SciElo in the period between 2000 and 2012. Keywords were leptin, substance use disorders, craving and withdrawal, in Portuguese and English. Only 12 articles were met the inclusion criteria, relating leptin with craving in alcoholics (n = 10) and smokers (n = 2). No studies were found in the LILACS database. Leptin levels increase during abstinence and this may be related to a reduction of dopaminergic action in mesolimbic system, resulting in a greater intensity of craving and maintenance of addictive behavior. Although there are few studies, the most recent results indicate the usefulness of leptin as a marker of risk for relapse among smokers and alcoholics in abstinence. PMID:23671541

  12. Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids.

    Science.gov (United States)

    Smith, Jeremy T; Waddell, Brendan J

    2003-07-01

    Leptin is essential for the establishment of pregnancy and appears to promote fetal growth, but the mechanisms regulating fetal leptin exposure remain unclear. In rodents, indirect evidence suggests that fetal leptin is partly derived from the maternal circulation via transplacental passage. Indeed, the placenta expresses mRNA for Ob-Ra, one of the short forms of the leptin receptor (Ob-R(S)) important in leptin transport, and this expression increases markedly in late pregnancy. Therefore, we determined the transplacental passage of maternal leptin to the fetus in the rat and whether this transport increases near term in association with a rise in placental expression of Ob-R(S) protein. Because of the proposed role of leptin in promoting fetal growth, we also assessed the effect of glucocorticoid-induced fetal growth retardation on placental leptin transport. Anesthetized rats received a constant infusion of (125)I-leptin via a jugular cannula before and at d 16 and 22 of pregnancy (term = d 23); plasma samples were obtained at 10, 20, 40, 60, 80, and 100 min, and fetuses and placentas were collected at the time of the final sample. The metabolic clearance rate of leptin fell (P pregnancy. Over this same period, Ob-R(S) protein expression in the placental labyrinth zone increased by almost 2-fold. Transplacental leptin passage was reduced (P pregnancy. Consistent with the proposed role of leptin as a fetal growth factor, transplacental leptin passage is reduced in association with glucocorticoid-induced fetal growth retardation.

  13. Relationship between Plasma Leptin Level and Chronic Kidney Disease

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    Anoop Shankar

    2012-01-01

    Full Text Available Background. Leptin is an adipose tissue-derived hormone shown to be related to several metabolic, inflammatory, and hemostatic factors related to chronic kidney disease. Recent animal studies have reported that infusion of recombinant leptin into normal rats for 3 weeks fosters the development of glomerulosclerosis. However, few studies have examined the association between leptin and CKD in humans. Therefore, we examined the association between plasma leptin levels and CKD in a representative sample of US adults. Methods. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n=5820, 53.6% women. Plasma leptin levels were categorized into quartiles (≤4.3 Fg/L, 4.4–8.7 Fg/L, 8.8–16.9 Fg/L, >16.9 Fg/L. CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m2 estimated from serum creatinine. Results. Higher plasma leptin levels were associated with CKD after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index (BMI, diabetes, hypertension, and serum cholesterol. Compared to quartile 1 of leptin (referent, the odds ratio (95% confidence interval of CKD associated with quartile 4 was 3.31 (1.41 to 7.78; P-trend = 0.0135. Subgroup analyses examining the relation between leptin and CKD by gender, BMI categories, diabetes, and hypertension status also showed a consistent positive association. Conclusion. Higher plasma leptin levels are associated with CKD in a representative sample of US adults.

  14. Creating leptin-like biofunctions by active immunization against chicken leptin receptor in growing chickens.

    Science.gov (United States)

    Lei, M M; Wu, S Q; Shao, X B; Li, X W; Chen, Z; Ying, S J; Shi, Z D

    2015-01-01

    In this study, immunization against chicken leptin receptor (cLEPR) extracellular domain (ECD) was applied to investigate leptin regulation and LEPR biofunction in growing chicken pullets. A recombinant protein (cLEPR ECD) based on the cLEPR complemenary DNA sequence corresponding to the 582nd to 796th amino acid residues of cLEPR mature peptide was prepared and used as antigen. Immunization against cLEPR ECD in growing chickens increased anti-cLEPR ECD antibody titers in blood, enhanced proportions of phosphorylated janus kinase 2 (JAK2) and served as signal transducer and activator of transcription 3 (STAT3) protein in liver tissue. Chicken live weight gain and abdominal fat mass were significantly decreased (P chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Leptin signaling molecular actions and drug target in hepatocellular carcinoma

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    Jiang N

    2014-11-01

    Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

  16. Body Mass Influences Cortical Bone Mass Independent of Leptin Signaling

    OpenAIRE

    Iwaniec, U.T.; Dube, M.G.; Boghossian, S.; Song, H.; Helferich, W.G.; Turner, R.T.; Kalra, S.P.

    2008-01-01

    Obesity in humans is associated with increased bone mass. Leptin, a hormone produced by fat cells, functions as a sentinel of energy balance, and may mediate the putative positive effects of body mass on bone. We performed studies in male C57Bl/6 wild type (WT) and leptin-deficient ob/ob mice to determine whether body mass gain induced by high fat intake increases bone mass and, if so, whether this requires central leptin signaling. The relationship between body mass and bone mass and archite...

  17. Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

    OpenAIRE

    Profita, Mirella; Bruno,; Alessi,; Soresi,; Bonanno,; Riccobono,; Montalbano,; Albano,; Gjomarkaj,

    2011-01-01

    Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in infla...

  18. Neonatal exposure to leptin augments diet-induced obesity in leptin-deficient Ob/Ob mice.

    Science.gov (United States)

    Yura, Shigeo; Itoh, Hiroaki; Sagawa, Norimasa; Yamamoto, Hiroshi; Masuzaki, Hiroaki; Nakao, Kazuwa; Kawamura, Makoto; Mogami, Haruta; Ogawa, Yoshihiro; Fujii, Shingo

    2008-06-01

    Epidemiological evidence has revealed that undernutrition in utero is closely associated with obesity and related detrimental metabolic sequelae in adulthood. Recently, using a wild-type (wt) mouse model in which offspring were exposed to intrauterine undernutrition (UN offspring), we reported that the premature leptin surge during neonatal growth promotes lifelong changes in energy regulating circuitry in the hypothalamus, thus playing an important role in the development of pronounced obesity on a high-fat diet (HFD) in adulthood. Here, we further evaluate the essential involvement of leptin in the developmental origins of obesity using leptin-deficient ob/ob mice. We assessed the progression of obesity on an HFD in adult leptin-deficient ob/ob male mice that were exposed to intrauterine undernutrition by maternal food restriction (ob/ob UN offspring) or to leptin treatment during the neonatal period; this treatment is comparable to the premature leptin surge observed in the wt-UN offspring. On an HFD, the body weight of the male ob/ob UN offspring paralleled that of the ob/ob offspring exposed to normal intrauterine nutrition (ob/ob NN offspring). In contrast, early exposure to leptin in the ob/ob NN offspring during early neonatal growth reproduced the development of pronounced obesity on an HFD in adulthood. The presence of leptin and associated energy regulation are indispensable in the acceleration of obesity on an HFD caused by undernutrition in utero. The premature leptin surge plays an essential role in the developmental origins of obesity as a programming signal during the early neonatal period.

  19. Duplicated leptin receptors in two species of eel bring new insights into the evolution of the leptin system in vertebrates

    DEFF Research Database (Denmark)

    Morini, M.; Pasquier, J.; van den Thillart, G.

    2015-01-01

    subfunctionalization. Four-month fasting had no impact on the expression of leptins and LEPRs in control European eels. This might be related to the remarkable adaptation of silver eel metabolism to long-term fasting throughout the reproductive oceanic migration. In contrast, sexual maturation induced differential...... of the duplicated LEPRs in this species. This suggests an ancient and positive role of the leptin system in the vertebrate reproductive function. This study brings new insights on the evolutionary history of the leptin system in vertebrates. Among extant vertebrates, the eel represents a unique case of duplicated...

  20. cAMP/PKA regulates osteogenesis, adipogenesis and ratio of RANKL/OPG mRNA expression in mesenchymal stem cells by suppressing leptin.

    Directory of Open Access Journals (Sweden)

    Der-Chih Yang

    Full Text Available BACKGROUND: Mesenchymal stem cells (MSCs are a pluripotent cell type that can differentiate into adipocytes, osteoblasts and other cells. The reciprocal relationship between adipogenesis and osteogenesis was previously demonstrated; however, the mechanisms remain largely unknown. METHODS AND FINDINGS: We report that activation of PKA by 3-isobutyl-1 methyl xanthine (IBMX and forskolin enhances adipogenesis, the gene expression of PPARgamma2 and LPL, and downregulates the gene expression of Runx2 and osteopontin, markers of osteogenesis. PKA activation also decreases the ratio of Receptor Activator of the NF-kappaB Ligand to Osteoprotegerin (RANKL/OPG gene expression - the key factors of osteoclastogenesis. All these effects are mediated by the cAMP/PKA/CREB pathway by suppressing leptin, and may contribute to PKA stimulators-induced in vivo bone loss in developing zebrafish. CONCLUSIONS: Using MSCs, the center of a newly proposed bone metabolic unit, we identified cAMP/PKA signaling, one of the many signaling pathways that regulate bone homeostasis via controlling cyto-differentiation of MSCs and altering RANKL/OPG gene expression.

  1. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...... regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo...

  2. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    Science.gov (United States)

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Serum leptin is correlated to high turnover in osteoporosis.

    Science.gov (United States)

    Hipmair, Gunter; Böhler, Nikolaus; Maschek, Wilma; Soriguer, Federico; Rojo-Martínez, Gemma; Schimetta, Wolfgang; Pichler, Robert

    2010-01-01

    Clinical data have suggested that obesity protects against osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved by mediating an effect on bone metabolism. This study was conducted to investigate a possible relationship of leptin and bone turn-over in postmenopausal women with osteoporosis. We measured bone mineral density (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin and cross-laps in 44 patients with osteoporosis. The main group consisted of 32 postmenopausal women. Mean serum leptin was 13.1 microg/L and showed no statistically significant difference to the levels measured in a collective of normal persons adjusted for age and BMI. When related to serum cross-laps as markers of bone resorption, a positive correlation (pturnover serum bone markers, at least in postmenopausal women with osteoporosis.

  4. MOLECULAR CLONING OF OVINE cDNA LEPTIN GENE

    Directory of Open Access Journals (Sweden)

    CLAUDIA TEREZIA SOCOL

    2008-05-01

    Full Text Available An efficient bacterial transformation system suitable for cloning the coding sequence of the ovine leptin gene in E. coli DH5α host cells using the pGEMT easy vector it is described in this paper. The necessity of producing leptin is based on the fact that the role of this molecule in the animal and human organism is still unknown, leptin not existing as commercial product on the Romanian market. The results obtained in the bacterial transformation, cloning, recombinant clones selection, control of the insertion experiments and DNA computational analysis represent the first steps in further genetic engineering experiments such as production of DNA libraries, DNA sequencing, protein expression, etc., for a further contribution in elucidating the role of leptin in the animal and human organism.

  5. Leptin in milk and plasma of dairy asses

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    F. Fantuz

    2010-04-01

    Full Text Available Milk and plasma leptin levels have been studied in dairy asses machine milked according to two different routines: 20 pregnant, pluriparous asses, were divided into two groups subjected, every 28 d for 150 d, to two consecutive milkings carried out at different intervals, i.e. 20 vs. 4 hours interval, respectively for group A and group B. During the study, the declining total milk obtained by machine milking was unaffected by the different milking strategies; body condition score of asses as well did not vary between the groups. Different milking intervals did not significantly influence skimmed milk leptin content neither plasma leptin level. Moreover, we did not find significant variation in plasma leptin neither correlation with BCS, indicating that in donkey pregnancy inhibits the cross talk between hypothalamus and adipose tissue.

  6. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...

  7. Serum leptin concentration in patients with type 2 diabetes

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    Malecha-Jedraszek Arleta

    2015-12-01

    Full Text Available With the increasing importance of early type 2 diabetes (DM2 and obesity detection, it is useful to reevaluate leptin role in these conditions. Our study aimed at investigating circulating leptin concentrations in a group of patients with DM2, and at assessing in detail whether leptin concentrations correlate with selected biochemical, clinical parameters and markers of systemic inflammation in patients with DM2 and in healthy volunteers. In our work, we analysed samples and data drawn from 71 patients aged 61.4 ± 11.7 years, who have been diagnosed with type 2 diabetes, as well as from a healthy control group (HC consisting of 51 healthy subjects with a mean age of 57.8 ± 13.7 years. Therein, the concentration of leptin in the DM2 patients was significantly higher than in the HC (p < 0.01, with median value of 16.59 (IQR 8.58-33.39 ng/ml in the DM2, vs median value of 6.66 (IQR 4.52-21.40 ng/ml in the HC. In the analysis of variance, higher leptin concentrations were revealed in the DM2 group as compared to the HC, and this figure remained significant after adjusting for gender and age (p < 0.001. Moreover, it was independent of HOMA-IR (p = 0.003. However, the differences in leptin levels between the groups disappeared when additional adjustments for anthropometric parameters (BMI, waist circumference were applied (p = 0.088. Beyond the aforementioned, significant positive correlations were found in the DM 2 group between leptin level and CRP (r=0.256; p < 0.05 and IL-6 (r = 0.345; p < 0.01. Among the selected variables, only gender and BMI were included in the predictive model explaining the variability of leptin, and, in total, were responsible for 72.6% of the original variation of the studied adipocytokine. The results of this study have led to conclusion that leptin may participate in the complex pathogenesis of DM2 and be a predictor of the development of this disease. As higher concentrations of leptin coexist with obesity, and this

  8. Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus.

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    Damien eGuimond

    2014-08-01

    Full Text Available It is becoming increasingly clear that leptin is not only a hormone regulating energy homeostasis but also a neurotrophic factor impacting a number of brain regions, including the hippocampus. Although leptin promotes the development of GABAergic transmission in the hypothalamus, little is known about its action on the GABAergic system in the hippocampus. Here we show that leptin modulates GABAergic transmission onto developing CA3 pyramidal cells of newborn rats. Specifically, leptin induces a long-lasting potentiation (LLP-GABAA of miniature GABAA receptor-mediated postsynaptic current (GABAA-PSC frequency. Leptin also increases the amplitude of evoked GABAA-PSCs in a subset of neurons along with a decrease in the coefficient of variation and no change in the paired-pulse ratio, pointing to an increased recruitment of functional synapses. Adding pharmacological blockers to the recording pipette showed that the leptin-induced LLP-GABAA requires postsynaptic calcium released from internal stores, as well as postsynaptic MAPK/ERK kinases 1 and/or 2 (MEK1/2, phosphoinositide 3 kinase (PI3K and calcium-calmodulin kinase kinase (CaMKK. Finally, study of CA3 pyramidal cells in leptin-deficient ob/ob mice revealed a reduction in the basal frequency of miniature GABAA-PSCs compared to wild type littermates. In addition, presynaptic GAD65 immunostaining was reduced in the CA3 stratum pyramidale of mutant animals, both results converging to suggest a decreased number of functional GABAergic synapses in ob/ob mice. Overall, these results show that leptin potentiates and promotes the development of GABAergic synaptic transmission in the developing hippocampus likely via an increase in the number of functional synapses, and provide insights into the intracellular pathways mediating this effect. This study further extends the scope of leptin’s neurotrophic action to a key regulator of hippocampal development and function, namely GABAergic transmission.

  9. Evaluation of Serum Leptin Level in Children With Acute Leukemia

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    Iraj Shahramian

    2016-01-01

    Full Text Available Background Leptin is a multifunctional hormone plays an important role in regulating lipid, energy, homeostasis, angiogenesis, inflammation, hematopoiesis and cell cycle. This polypeptide is effective in growth and differentiation of leukemic cells through an Ob-R receptor expressed by them. Objectives The purpose of this study was to evaluate serum leptin levels in patients with acute leukemia and compare it in lymphoid and myeloid groups. Patients and Methods This analytical case-control study, conducted on 60 children in age ranged from 6 months to 16 years in two case and control groups in Ali ibn Abi Talib hospital, Zahedan. They matched based on age and gender and examined after their parent’s satisfaction according to the parental consent forms. None of patients had heart disease, digestive, glandular and metabolic problems, iron deficiency anemia and chronic kidney disease. After collecting the samples, leptin levels of both groups were measured with ELISA kit. Then, the gathered data were analyzed in SPSS-20 software, using independent t-test in considering of 95% confidence interval. Results Leptin serum levels in patients with acute leukemia and controls showed significant difference (P < 0.05. Leptin serum levels in patients with acute lymphoblastic leukemia and acute myeloblastic leukemia showed significant difference (P < 0.05. Leptin serum level in relation to age and gender groups was not statistically significant. Conclusions The findings of this study showed that in patients with acute leukemia, leptin serum levels increase independently of age and gender. In addition, leptin serum levels in acute lymphoid leukemia were higher than acute myeloid leukemia in this study.

  10. Effect of body mass index on serum leptin levels

    International Nuclear Information System (INIS)

    Paul, R.F.; Hassan, M.; Nazar, H.S.

    2012-01-01

    Background: Leptin is product of ob gene, an adipose tissue derived hormone that plays a key role in the regulation of body fat mass by regulating appetite and metabolism while balancing energy intake and energy expenditure. The objective of the study was to evaluate possible association between serum leptin levels and Body Mass Index (BMI) of gender in adult age group. Methods: Two-hundred-seventy subjects aged 20-50 years were randomly selected from general population of Abbottabad. The subjects were grouped on the basis on BMI (89 normal, 92 overweight, and 89 obese). After complete evaluation, demographic data was recorded and BMI. Non-fasting venous blood samples were drawn to measure serum leptin and serum glucose levels. The data were analysed using SPSS-15 calculating mean, percentage, independent t-test and chi-square test. Correlation and regression curve analysis were obtained, and p and r values were calculated. Results: Serum leptin levels and differences between genders were significant in all body mass indices. For normal BMI group the mean values for leptin were 2.6+-1.5 gamma g/ml in men, and 17.3+9-10.2 gamma g/ml for women. For Group-2 mean leptin levels in men were 9.9+-6.8 gamma g/ml and in women were 34.8+-13.6 gamma g/ml. For Group-3 BMI comprising obese subjects mean values for men were 21.3+-14.2 gamma g/ml and for women were 48.21+-21.2 gamma g/ml (p<0.001). Conclusion: A progressive increase in serum leptin concentration was observed with an increase in BMI. Significant difference between leptin concentrations in either gender was found in normal, overweight and obese subjects. (author)

  11. Longitudinal Analysis of Leptin Variation during Weight Regain after Weight Loss in Obese Children

    DEFF Research Database (Denmark)

    Jens-Christian, Holm; Michael, Gamborg; Leigh, Ward

    2009-01-01

    . Results: Children with the greatest increases in BMI standard deviation score (SDS) exhibited the largest leptin increments. The disproportionate reduction of leptin seen during weight loss recovered after weight loss. Leptin increases mirrored increases in BMI SDS during weight regain, and the leptin......-BMI SDS relationship seen during follow-up resembled the baseline leptin-BMI SDS relationship. Conclusion: Proportional increases of leptin and BMI SDS during weight regain suggests an intact leptin response during re-accumulation of fat. Following the pronounced reduction of leptin during weight loss......Objective: This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control. Methods: 115 children were investigated during a 12-week weight loss program. 90 children completed the program...

  12. Longitudinal Analysis of Leptin Variation during Weight Regain after Weight Loss in Obese Children

    DEFF Research Database (Denmark)

    Holm, Jens-Christian; Gamborg, Michael; Ward, Leigh

    2009-01-01

    -BMI SDS relationship seen during follow-up resembled the baseline leptin-BMI SDS relationship. Conclusion: Proportional increases of leptin and BMI SDS during weight regain suggests an intact leptin response during re-accumulation of fat. Following the pronounced reduction of leptin during weight loss......Objective: This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control. Methods: 115 children were investigated during a 12-week weight loss program. 90 children completed the program....... Results: Children with the greatest increases in BMI standard deviation score (SDS) exhibited the largest leptin increments. The disproportionate reduction of leptin seen during weight loss recovered after weight loss. Leptin increases mirrored increases in BMI SDS during weight regain, and the leptin...

  13. Longitudinal Analysis of Leptin Variation during Weight Regain after Weight Loss in Obese Children

    DEFF Research Database (Denmark)

    Jens-Christian, Holm; Michael, Gamborg; Leigh, Ward

    2009-01-01

    Objective: This study assessed if lower than predicted serum leptin concentrations seen during weight loss persisted during weight regain, with possible implications for weight control. Methods: 115 children were investigated during a 12-week weight loss program. 90 children completed the program....... Results: Children with the greatest increases in BMI standard deviation score (SDS) exhibited the largest leptin increments. The disproportionate reduction of leptin seen during weight loss recovered after weight loss. Leptin increases mirrored increases in BMI SDS during weight regain, and the leptin......-BMI SDS relationship seen during follow-up resembled the baseline leptin-BMI SDS relationship. Conclusion: Proportional increases of leptin and BMI SDS during weight regain suggests an intact leptin response during re-accumulation of fat. Following the pronounced reduction of leptin during weight loss...

  14. Does leptin play a cytokine-like role within the airways of COPD patients?

    Science.gov (United States)

    Bruno, A; Chanez, P; Chiappara, G; Siena, L; Giammanco, S; Gjomarkaj, M; Bonsignore, G; Bousquet, J; Vignola, A M

    2005-09-01

    The leptin-leptin receptor system might be up-regulated in the airways of chronic obstructive pulmonary disease (COPD). In bronchial biopsies obtained from normal subjects and smokers, with and without COPD, the present study examined leptin and leptin-receptor expression and their co-localisation in airway and inflammatory cells. Combining immunohistochemistry with terminal deoxynucleotidyl transferase dUTP nick end-labelling techniques, apoptosis in airway and inflammatory cells and in leptin and leptin-receptor expressing cells was investigated. In the epithelial cells both leptin and leptin-receptor expression was higher in normal subjects than in smokers and COPD subjects. By contrast, in the sub-mucosa, leptin was over-expressed in COPD when compared with normal subjects and smokers. Leptin and its receptor were co-localised, mainly with activated T cells (CD45R0) and CD8+ T lymphocytes. In smokers, apoptosis was found in some inflammatory cells, whereas in COPD inflammatory cells, leptin and leptin-receptor positive cells were not apoptotic. Leptin expression was related to COPD severity and assessed using the Global initiative for Chronic Obstructive Lung Disease classification. In conclusion, the present study shows an increased leptin expression in bronchial mucosa of chronic obstructive pulmonary disease patients, associated with airway inflammation and airflow obstruction.

  15. Hantaran Sinyal Leptin dan Obesitas: Hubungannya dengan Penyakit Kardiovaskuler

    Directory of Open Access Journals (Sweden)

    David Limanan

    2013-11-01

    Full Text Available Diperkirakan saat ini jumlah orang dengan obesitas melebihi 250 juta orang, yaitu 7% dari populasi orang dewasa di dunia. Mortalitas obesitas erat hubungannya dengan sindrom metabolik yang merupakan kelainan metabolik meliputi obesitas, resistensi insulin, gangguan toleransi glukosa, abnormalitas trigliserida dan hemostasis, disfungsi endotel dan hipertensi. Leptin dihasilkan adiposit dan merupakan anggota dari adipositokin; berperan dalam hantaran sinyal hormon jaringan adiposa. Kelainan leptin maupun reseptornyadapat menyebabkan seseorang mengalami obesitas, metabolik sindrom, diabetes dan penyakit kardiovaskuler. Kompleks leptin-reseptor mengaktifkan sistem transduksi sinyal, yang paling dominan adalah jalur janus kinase-signal transducer and activator of transcription-3 (JAK-STAT3, kemudian phospatidyl inositol 3- kinase (PI3K, mitogen-activated protein kinase (MAPK, 5’adenosine monophosphate-activated protein kinase (AMPK, dan mammalian target of rapamycin (mTOR. Jalur leptin-associated PI3K dengan ERK cascade berperan penting dalam proliferasi kardiomiosit dan melindungi jantung dari ischemia reperfusion injury. ERK1/2 mengaktifkan target gen seperti c-fos dan egr-1 yang berperan dalam proliferasi dan diferensiasi. Nuclear factor κB diduga sebagai target jalur p38 dan JNK MAPK. Faktor transkripsi inu berperan pentingdalam mengatur transkripsi sitokin proinflamasi seperti tumor necrosis factor (TNF-α dan interleukin (IL-1β. Leptin dapat meningkatkan pembentukan reactive oxygen species (ROS sel endotel pembuluh darah dan menstimulasi sekresi TNF-α dan IL-6 yang merupakan promotor hipertensi dan aterosklerosis.Kata Kunci: obesitas, leptin, sistem kardiovaskuler 

  16. Serum leptin levels in patients with coronary artery disease

    International Nuclear Information System (INIS)

    Akram, S.; Ahmed, Z.; Fayyaz, I.; Mehmood, S.; Chani, M.

    2011-01-01

    Cardiovascular diseases (CVD) are the leading cause of morbidity, mortality and disability worldwide. Leptin, a 16kDa product of ob gene, is an endocrine hormone produced by white adipose tissue. It is primarily involved in the regulation of food intake and energy expenditure. Hyperleptinemia is one of the novel risk factors contributing in many ways to CVD. Objective: The objective of the study was to find the level of leptin in patients with coronary artery disease (CAD) and compare it with healthy people in our population. Methods: Our study was an analytical and cross-sectional study. Our study included 60 patients with a history of CAD and 60 healthy controls (aged 40-60 years, both sexes). Leptin levels were measured by ELISA. Results: Mean serum leptin level in patients was 11.48+-11.25 g/ml, while control group had a mean leptin level of 8.22+-8.01 g/ml (p=0.071). Conclusion: Leptin levels were higher in patients but the difference was non-significant. More studies are needed with larger sample size in our population. (author)

  17. The relationship between umbilical and maternal blood leptin and it's effect in fetal growth

    International Nuclear Information System (INIS)

    Chen Linqi; Guo Sheng; Yu Xin; Feng Xing

    2005-01-01

    Objective: To study the correlation of leptin between maternal serum and cord blood and to know relationship between leptin and fetal growth, and the origin of leptin. Methods: The concentration of leptin in 55 cases of maternal serum and cord arterial and venous blood were measured by ELISA assay. According to the neonatal weight and gestational age, three groups were divided into small gestational age (SGA), appropriate gestational age (AGA) and large gestational age (LGA). The nutrition status of neonatal was evaluated by index of Pondernal. The comparision was made in these groups. Results: The concentration of leptin in the cord artery, venous and maternal serum among 55 cases was 16.58 ± 8.13 ng/ml, 12.05 ± 9.87 ng/ml, 13.24 ± 10.58 ng/ml respectively; The concentration of maternal serum leptin was higher than that of cord artery. The concentration of maternal serum leptin was higher than that of venous serum leptin slightly. There was significant difference between cord artery and venous in different gestational age groups. Serum leptin levels of cord artery and venous were well correlated with the one of the weight and gestational age of neonatal. Maternal serum leptin level was not correlated with birth weight, placental weight and gestational age. Conclusions: The leptin from placenta is concerned with the adjustment of fetal growth. Cord leptin can reflect the status of fetal growth. Cord venous leptin indicate that the leptin be from placenta. Cord artery leptin demonstrates a part of placenta leptin, which acts on the fetus and then induces the fetal fat tissue to produce leptin. The maternal leptin does not adjust fetal weight directly. It only adjusts fat content itself and energy metabolism. (authors)

  18. The effect of four weeks restricted diet on serum soluble leptin receptor levels and adipocyte leptin receptor density in normoweight rattus norvegicus strain Wistar

    Directory of Open Access Journals (Sweden)

    M. R. Indra

    2006-09-01

    Full Text Available One of the five possible mechanisms of leptin resistance in human obesity is the defect in the leptin receptor (Ob-R. Evidence has accumulated that leptin-binding activity in human serum is related to a soluble form of the leptin receptor, and restriction of energy intake resulted a decrease in circulating leptin levels. Aim of this study is to examine the difference of serum soluble leptin receptor level and leptin receptor density in rat adipose tissue of adventitial aorta after four weeks treated with different restricted diets. Soluble leptin receptor level was measured by ELISA and leptin receptor density by using immuno-histochemistry. The soluble leptin receptor in group treated with 40% of normal daily calori diet was found significantly lower than control (p = 0.02. There were no any significant differences among group treated with 40 % of normal daily calori diet, “1 day fast-1day eat”, and ”1day fast-2 days eat” groups, and among 1 day fast-1 day eat”, ”day fast - 2 days eat” and control groups as well. On the other hand, leptin receptor density in adipose tissues was higher in restricted diet group than control. Diet of 40 % normal daily calorie for 4 weeks decreased soluble leptin receptor level, but increased adipocyte leptin receptor density of the adipose tissue of rat adventitial aorta. These changes may be resulted from an up regulation mechanism in relation with homeostatic maintenance. (Med J Indones 2006; 15:145-50 Keywords: restricted diet, leptin receptor, soluble leptin receptor, adipocyte, obesity

  19. Residues in the 5th module of the low-density lipoprotein receptor that bind apoE and apoB-100

    International Nuclear Information System (INIS)

    Kroon, P.A.; Zhang, H.-Y.; Smith, R.

    2000-01-01

    Full text: The low-density lipoprotein receptor (LDLR) binds and removes cholesterol-rich lipoproteins from the circulation. Its ligand-binding (LB) domain consists of seven cysteine-rich LB modules that bind apoB-100 and apoE. These modules fold into well-defined structures with three disulfide bonds, in the presence of Ca 2+ . The 5th module (LB5) is unique in that it is required to bind both apoB-100 and apoE. The aim of the current study was to map residues in human LB5 that are required for ligand binding. This was done by alanine mutagenesis of a series of residues that are conserved in human, mouse, rat and rabbit LB5 (E9, S14, E16, H19, S21, K31, and K33), but not in the other six modules. E37 (R37 in the rabbit) was included, since it has been previously hypothesized to play a role in binding. The variant LB5 modules were first produced as recombinant peptides, and subjected to oxidative folding to determine whether the mutations interfered with Ca 2+ '-dependent folding. Only the S14A and E16A mutations interfered significantly with folding, suggesting that S14 and E16 are required for the structural framework of LB5 and that their substitution in the LDLR may interfere with its folding. The native LDLR and E9A, H19A, S21A, K31A, K33A and E37A LDLRs were expressed in LDLR negative IdlA-7 CHO cells. Labeling with 125 I-lgG-C7 showed that all receptors were expressed on the cell surface. Binding of Dil-labeled LDL (Dil-LDL) and Dil-labeled DMPC, complexed with the N-terminal receptor-binding domain of apoE3 (Dil-E3), at 4 deg C, was used to assess receptor binding. Binding of Dil-E3 (0.1 μ/ml) to the H19A, S21A, K31A, K33A and E37A LDLRs was 65-92% of binding to the native LDLR. In contrast, the E9A LDLR only bound 3% of that of the native LDLR. The binding of Dil-LDL (0.5 Ag/ml) to the E9A LDLR was 23% of that of the native LDLR, while binding to the remaining variant LDLRs ranged from 44-70% of what of the native LDLR. We conclude that (i) E9 of LB5

  20. Relationship between expression of leptin receptors mRNA in breast tissue, plasma leptin level in breast cancer patients with obesity and clinical pathologic data

    International Nuclear Information System (INIS)

    Li Chunrui; Liu Wenli; Sun Hanying; Zhou Jianfeng

    2007-01-01

    In order to investigate the expression of leptin receptors mRNA in breast tissue and plasma leptin levels in breast cancer patients with obesity and their relationship with clinical pathologic data, 124 subjects who were either obesity or had suffered from breast benign disease with obesity, or breast cancer with obesity were entered into this study. The levels of plasma leptin in all subjects were determined and leptin receptors mRNA expression levels were measured by RT-PCR in breast tissue of breast cancer patients with obesity and breast benign disease with obesity. The results showed that plasma leptin levels in breast cancer patients with obesity were significantly higher than those in breast benign disease with obesity and obesity patients alone (P<0.05). The expression of the leptin receptor long form [-Lep-R(L)-] mRNA and the leptin receptor short form [-Lep-R(S)-] mRNA in breast tissue of breast cancer patients with obesity were significantly higher than that in breast tissue of breast benign disease patients with obesity (P<0.05). The plasma leptin level had remarkable positive correlation with the expressions of the Lep-R(L) mRNA and the Lep-R(S) mRNA. The plasma leptin level and leptin receptors mRNA expression levels in patients were not correlated with the axillary node metastasis, menopause, the TNM stage or pathological type. Therefore, leptin may have a promoting effect on the carcinogenesis of breast cancer. (authors)

  1. Circulating leptin and body composition in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Karakas, S; Karadag, F; Karul, A B; Gurgey, O; Gurel, S; Guney, E; Cildag, O

    2005-10-01

    Nutritional depletion and weight loss are two features of chronic obstructive pulmonary disease (COPD), and the association between low body mass index (BMI) and poor prognosis in patients with COPD is a common clinical observation. Mechanisms of weight loss are still unclear in COPD. Excessive energy expenditure partly due to increased work of breathing was shown, but other mechanisms have been searched for. Leptin is a hormone secreted by adipocytes that plays an important role in energy homeostasis and regulates body weight through control of appetite and energy expenditure. The aim of this study was to evaluate the association of circulating leptin levels and measures of body composition in COPD patients. Thirty male COPD outpatients (mean age 66.3 +/- 8.4) and 20 controls (mean age 65.9 +/- 10.8) were included in the study. After standard spirometry and body composition measurements, serum leptin concentration was measured by ELISA assay. COPD patients were grouped according to BMI. Mean BMI was 19.01 +/- 2.26 kg/m2 in group 1 (COPD patients with low BMI), 26.85 +/- 4.51 in group 2 COPD (COPD patients with normal/high BMI) and 27.64 +/- 2.75 kg/m2 in healthy controls (group 3). Mean serum leptin concentration was 1.41 +/- 1.86 ng/ml in group 1, 2.60 +/- 1.38 ng/ml in group 2 and 2.82 +/- 1.46 ng/ml in group 3 (p = 0.002). Leptin correlated to not only BMI but also body weight, waist circumference, triceps and biceps skinfold thickness and body fat percent (p leptin in COPD. Instead, leptin remains regulated in COPD and further decreased in patients with low BMI, probably as a compensatory mechanism to preserve body fat content, which should be evaluated in further studies.

  2. Serum leptin concentration during puberty in healthy nonobese adolescents

    Directory of Open Access Journals (Sweden)

    Brandão C.M.A.

    2003-01-01

    Full Text Available Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age, representing all pubertal stages. We excluded individuals with a body mass index (BMI below the 5thor above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80 presented a positive linear correlation with age (r = 0.35, P = 0.0012, BMI (r = 0.65, P < 0.0001 and %fat mass (r = 0.76, P < 0.0001. In boys (N = 95 there was a positive correlation with BMI (r = 0.49, P < 0.0001 and %fat mass (r = 0.85, P < 0.0001, but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001 and age (r = -0.40, P < 0.0001. The regression equation revealed that %fat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or %fat mass to assure a correct evaluation.

  3. Influence of weeks of circadian misalignment on leptin levels

    Directory of Open Access Journals (Sweden)

    June Nguyen

    2009-12-01

    Full Text Available June Nguyen, Kenneth P Wright JrDepartment of Integrative Physiology, Sleep and Chronobiology Laboratory, University of Colorado, Boulder, CO, USAAbstract: The neurobiology of circadian, wakefulness–sleep, and feeding systems interact to influence energy homeostasis. Sleep and circadian disruptions are reported to be associated with increased risk of diabetes and obesity, yet the roles of energy balance hormones in these associations are largely unknown. Therefore, in the current study we aimed to assess the influence of several weeks of circadian misalignment (sleep and wakefulness occurring at an inappropriate biological time on the anorexigenic adipocyte hormone leptin. We utilized data from a previous study designed to assess physiological and cognitive consequences of changes in day length and light exposure as may occur during space flight, including exploration class space missions and exposure to the Martian Sol (day length. We hypothesized that circadian misalignment during an exploration class spaceflight simulation would reduce leptin levels. Following a three-week ~8 hours per night home sleep schedule, 14 healthy participants lived in the laboratory for more than one month. After baseline data collection, participants were scheduled to either 24.0 or 24.6 hours of wakefulness–sleep schedules for 25 days. Changes in the phase of the circadian melatonin rhythm, sleep, and leptin levels were assessed. Half of participants analyzed exhibited circadian misalignment with an average change in phase angle from baseline of ~4 hours and these participants showed reduced leptin levels, sleep latency, stage 2 and total sleep time (7.3 to 6.6 hours and increased wakefulness after sleep onset (all P < 0.05. The control group remained synchronized and showed significant increases in sleep latency and leptin levels. Our findings indicate that weeks of circadian misalignment, such as that which occurs in circadian sleep disorders, alters leptin

  4. In Uncontrolled Diabetes, Hyperglucagonemia and Ketosis Result From Deficient Leptin Action in the Parabrachial Nucleus.

    Science.gov (United States)

    Meek, Thomas H; Matsen, Miles E; Faber, Chelsea L; Samstag, Colby L; Damian, Vincent; Nguyen, Hong T; Scarlett, Jarrad M; Flak, Jonathan N; Myers, Martin G; Morton, Gregory J

    2018-04-01

    Growing evidence implicates neurons that project from the lateral parabrachial nucleus (LPBN) to the hypothalamic ventromedial nucleus (VMN) in a neurocircuit that drives counterregulatory responses to hypoglycemia, including increased glucagon secretion. Among LPBN neurons in this circuit is a subset that expresses cholecystokinin (LPBNCCK neurons) and is tonically inhibited by leptin. Because uncontrolled diabetes is associated with both leptin deficiency and hyperglucagonemia, and because intracerebroventricular (ICV) leptin administration reverses both hyperglycemia and hyperglucagonemia in this setting, we hypothesized that deficient leptin inhibition of LPBNCCK neurons drives activation of this LPBN→VMN circuit and thereby results in hyperglucagonemia. Here, we report that although bilateral microinjection of leptin into the LPBN does not ameliorate hyperglycemia in rats with streptozotocin-induced diabetes mellitus (STZ-DM), it does attenuate the associated hyperglucagonemia and ketosis. To determine if LPBN leptin signaling is required for the antidiabetic effect of ICV leptin in STZ-DM, we studied mice in which the leptin receptor was selectively deleted from LPBNCCK neurons. Our findings show that although leptin signaling in these neurons is not required for the potent antidiabetic effect of ICV leptin, it is required for leptin-mediated suppression of diabetic hyperglucagonemia. Taken together, these findings suggest that leptin-mediated effects in animals with uncontrolled diabetes occur through actions involving multiple brain areas, including the LPBN, where leptin acts specifically to inhibit glucagon secretion and associated ketosis.

  5. Associations of plasma leptin to clinical manifestations in reproductive aged female patients with panic disorder.

    Science.gov (United States)

    Masdrakis, Vasilios G; Papageorgiou, Charalambos; Markianos, Manolis

    2017-09-01

    Preclinical studies suggest the implication of the adipocyte hormone leptin in anxiety and fear processes. We explored for potential differences regarding plasma leptin, cortisol and the ratio leptin/Body Mass Index (BMI) between 27 medication-free female patients with Panic Disorder (PD) and 42 age-matched female controls, and for potential associations between plasma leptin and psychometric evaluations including number of panic attacks during last week, Clinical Global Impression-Severity of Illness (CGI-S) and Symptoms Checklist-90-Revised (SCL-90-R). Cortisol levels showed no differences between patients and controls, or correlations to leptin or to any clinical features. Both groups demonstrated a strong positive correlation between leptin and BMI and similar leptin and leptin/BMI, despite patients' lower BMI. However, patients -but not controls- demonstrated significant negative correlations of leptin to the 'somatization', 'anxiety', and 'phobic anxiety' SCL-90-R subscales. Moreover, there was a significant negative correlation of leptin and of leptin/BMI ratio to the number of panic attacks during last week, while higher CGI-S was associated with lower leptin/BMI ratio. Our results, limited to PD female patients, suggest that lower leptin serum levels are significantly associated with greater severity of psychopathological manifestations, including number of panic attacks, symptoms of somatization, anxiety and phobic anxiety and overall clinical presentation. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  6. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution

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    Sambavi Kugananthan

    2016-11-01

    Full Text Available Human milk (HM contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM (p < 0.0001, n = 287. No association was found between whole HM leptin and fat content (p = 0.17, n = 287, supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89. These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  7. Leptin Levels Are Higher in Whole Compared to Skim Human Milk, Supporting a Cellular Contribution.

    Science.gov (United States)

    Kugananthan, Sambavi; Lai, Ching Tat; Gridneva, Zoya; Mark, Peter J; Geddes, Donna T; Kakulas, Foteini

    2016-11-08

    Human milk (HM) contains a plethora of metabolic hormones, including leptin, which is thought to participate in the regulation of the appetite of the developing infant. Leptin in HM is derived from a combination of de novo mammary synthesis and transfer from the maternal serum. Moreover, leptin is partially lipophilic and is also present in HM cells. However, leptin has predominately been measured in skim HM, which contains neither fat nor cells. We optimised an enzyme-linked immunosorbent assay for leptin measurement in both whole and skim HM and compared leptin levels between both HM preparations collected from 61 lactating mothers. Whole HM leptin ranged from 0.2 to 1.47 ng/mL, whilst skim HM leptin ranged from 0.19 to 0.9 ng/mL. Whole HM contained, on average, 0.24 ± 0.01 ng/mL more leptin than skim HM ( p < 0.0001, n = 287). No association was found between whole HM leptin and fat content ( p = 0.17, n = 287), supporting a cellular contribution to HM leptin. No difference was found between pre- and post-feed samples (whole HM: p = 0.29, skim HM: p = 0.89). These findings highlight the importance of optimising HM leptin measurement and assaying it in whole HM to accurately examine the amount of leptin received by the infant during breastfeeding.

  8. Effects of chronic leptin administration on nitric oxide production and immune responsiveness of greenfinches.

    Science.gov (United States)

    Lõhmus, Mare; Sild, Elin; Hõrak, Peeter; Björklund, Mats

    2011-04-01

    Leptin and nitric oxide (NO) are both important messengers in intra- and intercellular communication systems in vertebrates. Several studies have demonstrated an involvement of both substances in the immune response. Here we tested the effects of chronic leptin and anti-leptin treatments on the NO production and phytohaemagglutinin- (PHA) induced cutaneous inflammatory response in a wild passerine, the greenfinch (Carduelis chloris). Plasma leptin levels of individual birds were consistent in time but could be still temporarily increased by administration of recombinant chicken leptin. Increase of plasma leptin was also induced by administration of anti-leptin, which can be most likely explained by increased endogenous leptin production due to disruption of signalling pathways. Contrary to previous findings in mammals, leptin administration reduced systemic NO production. Leptin increased cutaneous swelling response to PHA. This immune-enhancing effect was observable despite the similar plasma leptin levels of leptin-treated and control birds at the time of measurement of immune responses, i.e., 9 days after start of the treatments. This provides evidence for a delayed or long-term potentiation of the cells and cytokines involved. The effects of leptin administration on NO production and immune responsiveness were age-dependent, which indicates the complexity of underlying regulatory mechanisms. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Low serum leptin predicts mortality in patients with chronic kidney disease stage 5

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Rattensperger, Dirk; Zidek, Walter

    2007-01-01

    Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy....

  10. Deficiency of leptin receptor in myeloid cells disrupts hypothalamic metabolic circuits and causes body weight increase

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    Yuanqing Gao

    2018-01-01

    Conclusions: Myeloid cell leptin receptor deficient mice partially replicate the db/db phenotype. Leptin signaling in hypothalamic microglia is important for microglial function and a correct formation of the hypothalamic neuronal circuit regulating metabolism.

  11. High leptin levels are associated with migraine with aura.

    Science.gov (United States)

    Pisanu, Claudia; Preisig, Martin; Castelao, Enrique; Glaus, Jennifer; Cunningham, Janet L; Del Zompo, Maria; Merikangas, Kathleen R; Schiöth, Helgi B; Mwinyi, Jessica

    2017-04-01

    Background Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess the associations between serum leptin and adiponectin levels and migraine or migraine subtypes. Analyses were adjusted for a lifetime history of MDD in order to investigate the association between adipokines and migraine under consideration of depression status. Methods We included 3025 participants from the CoLaus/PsyCoLaus study. The impact of leptin and adiponectin levels on a diagnosis of migraine was analysed by binary regression analyses, adjusting for variables known to influence adipokine levels. Subgroup analyses were conducted based on the presence of aura. Results Crude leptin levels were significantly higher in subjects with migraine than controls (Mann-Whitney U = 515,102, p = 6 × 10 -7 ). When performing adjusted analyses, leptin levels were found to be significantly higher in subjects with migraine (odds ratio = 1.22, p = 0.024) and migraine with aura (odds ratio = 1.34, p = 0.004). Conclusion High leptin levels might play a role in the pathogenesis of migraine and migraine with aura.

  12. Circulating leptin in patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Takabatake, N; Nakamura, H; Abe, S; Hino, T; Saito, H; Yuki, H; Kato, S; Tomoike, H

    1999-04-01

    Unexplained weight loss is common in patients with chronic obstructive pulmonary disease (COPD). Since leptin, an obesity gene product, is known to play important roles in the control of body weight and energy expenditure, we investigated serum leptin levels, along with circulating tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptor (sTNF-R55 and -R75) levels, in 31 patients with COPD and 15 age-matched healthy controls. The body mass index (BMI) and percent body fat (%fat) were significantly lower in the COPD patients than in the healthy controls (BMI = 18.1 +/- 2.7 kg/m2 versus 22.8 +/- 2.2 kg/m2 [mean +/- SD]; p leptin levels were significantly lower in the COPD patients than in the healthy controls (1.14 +/- 1.17 ng/ml versus 2.47 +/- 2.01 ng/ml; p COPD patients than in the healthy controls. Importantly, circulating leptin levels (log transformed) did correlate well with BMI and %fat, but not with TNF-alpha or with sTNF-R levels in the COPD patients. These data suggest that circulating leptin is independent of the TNF-alpha system and is regulated physiologically even in the presence of cachexia in patients with COPD.

  13. Light Modulates Leptin and Ghrelin in Sleep-Restricted Adults

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    Mariana G. Figueiro

    2012-01-01

    Full Text Available Acute and chronic sleep restrictions cause a reduction in leptin and an increase in ghrelin, both of which are associated with hunger. Given that light/dark patterns are closely tied to sleep/wake patterns, we compared, in a within-subjects study, the impact of morning light exposures (60 lux of 633-nm [red], 532-nm [green], or 475-nm [blue] lights to dim light exposures on leptin and ghrelin concentrations after subjects experienced 5 consecutive days of both an 8-hour (baseline and a 5-hour sleep-restricted schedule. In morning dim light, 5-hour sleep restriction significantly reduced leptin concentrations compared to the baseline, 8-hour sleep/dim-light condition (1,32 = 2.9; =0.007. Compared to the 5-hour sleep/dim-light condition, the red, green, and blue morning light exposures significantly increased leptin concentrations (1,32 = 5.7; <0.0001, 1,32 = 3.6; =0.001, and 1,32 = 3.0; =0.005, resp.. Morning red light and green light exposures significantly decreased ghrelin concentrations (1,32 = 3.3; <0.003 and 1,32 = 2.2; =0.04, resp., but morning blue light exposures did not. This study is the first to demonstrate that morning light can modulate leptin and ghrelin concentrations, which could have an impact on reducing hunger that accompanies sleep deprivation.

  14. Anorexia of aging, leptin, and the Mini Nutritional Assessment.

    Science.gov (United States)

    Morley, J E; Miller, D K; Perry, H M; Patrick, P; Guigoz, Y; Vellas, B

    1999-01-01

    In this chapter we have reviewed the evidence for physiological anorexia of aging and stressed that its pathophysiology involves both central and peripheral mechanisms. Early satiation in the older person appears to involve signals predominantly arising in the stomach. The increased feeling of satiety in older persons is mainly related to changes in the central feeding drive, in particular a decrease in the opioid rewarding properties for fatty foods. Increased cytokines, secondary to inflammatory conditions which are common in old age, may further increase the anorexia seen in older persons. Leptin, the fat hormone, is an excellent indicator of fat mass in women, in whom leptin concentrations correlate with the MNA. In men, testosterone inhibits leptin, and the fall in testosterone with age results in an increase in leptin concentrations. In males the MNA is not related to leptin concentrations. Finally, we have examined the interrelation of two nutritional screening indices, MNA and SCALES. The two indices were well correlated and were both predictive of poor basic function. We conclude that the MNA is an excellent predictor of nutritional status. These findings suggest that malnutrition is a major predictor of frailty or the "failure to thrive" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons.

  15. The unique cysteine knot regulates the pleotropic hormone leptin.

    Directory of Open Access Journals (Sweden)

    Ellinor Haglund

    Full Text Available Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin.

  16. The association of serum leptin levels with metabolic diseases

    Directory of Open Access Journals (Sweden)

    Jen-Pi Tsai

    2017-01-01

    Full Text Available Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases. In addition, hyperleptinemia had been reported to contribute to renal diseases through multiple mechanisms resulting in glomerulopathy presenting with a decreased glomerular filtration rate, increased albuminuria, and related clinical symptoms, which are pathophysiological features of chronic kidney disease. Because these cardiovascular and metabolic disorders are great challenges for physicians, understanding the related pathophysiological association with leptin might become a valuable aid in handling patients in daily clinical practice. This review will discuss the roles of leptin in the regulation of biological functions of multiple organs beyond the maintenance of feeding and metabolism.

  17. Training, leptin receptors and SOCS3 in human muscle.

    Science.gov (United States)

    Olmedillas, H; Guerra, B; Guadalupe-Grau, A; Santana, A; Fuentes, T; Dorado, C; Serrano-Sanchez, J A; Calbet, J A L

    2011-05-01

    Endurance exercise induces SUPPRESSOR of CYTOKINE SIGNALING 3 (SOCS3) mRNA expression in rodent skeletal muscle and endurance training overimposed on strength training blunts the hypertrophic response to strength training by an unknown mechanism. The aim of this study was to determine the effects of a concurrent strength and endurance training on fat mass, serum leptin concentration, muscle morphology, and muscle vastus lateralis leptin receptors (OB-Rb) and SOCS3 protein expression. 16 healthy young men were assigned to a control (C; n=7), and to a 12-week weightlifting (3 sessions/week)+endurance training program (T; n=9) group. Training enhanced maximal dynamic strength in lower and upper body exercises (18-54%), reduced fat mass by 1.8 kg and serum leptin concentration per kg of fat mass, and elicited muscle hypertrophy of type 2 (+18.5%, Ptraining. In conclusion, concurrent strength and endurance training reduces fat mass and serum leptin and the ratio leptin/fat mass without significant effects on vastus lateralis OB-Rb protein expression. Training does not increase the basal expression of SOCS3 protein in humans. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

    International Nuclear Information System (INIS)

    Wu, Yi-meng; Luo, Han-wen; Kou, Hao; Wen, Yin-xian; Shen, Lang; Pei, Ling-guo; Zhou, Jin; Zhang, Yuan-zhen; Wang, Hui

    2015-01-01

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2. • Caffeine

  19. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    Science.gov (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  20. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    John S. Parks

    2013-07-01

    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  1. Role of leptin G-2548A polymorphism in age- and gender-specific ...

    Indian Academy of Sciences (India)

    2015-06-25

    Jun 25, 2015 ... ized to the hypothalamus. When the mass of adipose tissue increases, released leptin curtails appetite and stimulates energy expenditure. When the mass of adipose tissue de- creases, a lower leptin production favours an increase in appetite and less energy expenditure (Halaas et al. 1995). Thus, leptin is ...

  2. The diversity of leptin gene in Iranian native, Holstein and Brown ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... This study describes genetic variability in the leptin in Iranian native, Brown Swiss and Holstein cattle. (Bos Indicus and Bos Taurus). This is the first study of genetic polymorphism of the leptin gene in. Iranian native cattle. We examined exon 2 of the leptin gene from 587 individuals in six different.

  3. Association between A59V polymorphism in exon 3 of leptin gene ...

    African Journals Online (AJOL)

    ONOS

    2010-09-06

    Sep 6, 2010 ... We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to screen for DNA polymorphisms of the leptin gene in 255 cows of Iranian Holstein. Amplified region is located in exon 3 of leptin gene. The genomic bovine leptin sequences, which consist of three ...

  4. Effects of administration of glucocorticoids and feeding status on plasma leptin concentrations in dogs.

    Science.gov (United States)

    Nishii, Naohito; Takasu, Masaki; Ohba, Yasunori; Maeda, Sadatoshi; Kitoh, Katsuya; Ohtsuka, Yoshihiko; Honjo, Tsutomu; Saito, Masayuki; Kitagawa, Hitoshi

    2006-02-01

    To investigate effects of short- and long- term administration of glucocorticoids, feeding status, and serum concentrations of insulin and cortisol on plasma leptin concentrations in dogs. 20 nonobese dogs. For experiment 1, plasma leptin concentrations and serum concentrations of insulin and cortisol were monitored for 24 hours in 4 dogs administered dexamethasone (0.1 mg/kg, IV) or saline (0.9% NaCl) solution for fed and nonfed conditions. For experiment 2, 11 dogs were administered prednisolone (1 mg/kg, PO, q 24 h for 56 days [7 dogs] and 2 mg/kg, PO, q 24 h for 28 days [4 dogs]) and 5 dogs served as control dogs. Plasma leptin and serum insulin concentrations were monitored weekly. For experiment 1, dexamethasone injection with the fed condition drastically increased plasma leptin concentrations. Furthermore, injection of saline solution with the fed condition increased plasma leptin concentrations. These increases in plasma leptin concentrations correlated with increases in serum insulin concentrations. Dexamethasone injection with the nonfed condition increased plasma leptin concentrations slightly but continuously. Injection of saline solution with the nonfed condition did not alter plasma leptin concentrations. For experiment 2, prednisolone administration at either dosage and duration did not alter plasma leptin concentrations in any dogs. Dexamethasone injection and feeding increased plasma leptin concentrations in dogs. In addition, dexamethasone administration enhanced the effect of feeding on increases in plasma leptin concentrations. Daily oral administration of prednisolone (1 or 2 mg/kg) did not affect plasma leptin concentrations in dogs.

  5. Placental ghrelin and leptin expression and cord blood ghrelin, adiponectin, leptin, and C-peptide levels in severe maternal obesity.

    Science.gov (United States)

    Allbrand, Marianne; Åman, Jan; Lodefalk, Maria

    2017-08-08

    The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables. Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA. Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r = 0.424, p = .016) and in the infants born to normal-weight women with their weight z-scores at six (r = -0.642, p = .010), nine (r = -0.441, p = .015), and 12 months of age (r = -0.402, p = .028). Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants' postnatal weight gain, but possibly only when the mother has normal weight.

  6. Hypothalamic CART is a new anorectic peptide regulated by leptin.

    Science.gov (United States)

    Kristensen, P; Judge, M E; Thim, L; Ribel, U; Christjansen, K N; Wulff, B S; Clausen, J T; Jensen, P B; Madsen, O D; Vrang, N; Larsen, P J; Hastrup, S

    1998-05-07

    The mammalian hypothalamus strongly influences ingestive behaviour through several different signalling molecules and receptor systems. Here we show that CART (cocaine- and amphetamine-regulated transcript), a brain-located peptide, is a satiety factor and is closely associated with the actions of two important regulators of food intake, leptin and neuropeptide Y. Food-deprived animals show a pronounced decrease in expression of CART messenger RNA in the arcuate nucleus. In animal models of obesity with disrupted leptin signalling, CART mRNA is almost absent from the arcuate nucleus. Peripheral administration of leptin to obese mice stimulates CART mRNA expression. When injected intracerebroventricularly into rats, recombinant CART peptide inhibits both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. An antiserum against CART increases feeding in normal rats, indicating that CART may be an endogenous inhibitor of food intake in normal animals.

  7. Plasma leptin levels in healthy children and adolescents

    DEFF Research Database (Denmark)

    Blum, W F; Englaro, P; Hanitsch, S

    1997-01-01

    difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender......Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine...... changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean...

  8. Plasma leptin levels in healthy children and adolescents

    DEFF Research Database (Denmark)

    Blum, W F; Englaro, P; Hanitsch, S

    1997-01-01

    increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin...... levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further......, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression...

  9. Mechanism of attenuation of leptin signaling under chronic ligand stimulation

    Directory of Open Access Journals (Sweden)

    Bamberg-Lemper Simone

    2010-01-01

    Full Text Available Abstract Background Leptin is an adipocyte-derived hormone that acts via its hypothalamic receptor (LEPRb to regulate energy balance. A downstream effect essential for the weight-regulatory action of leptin is the phosphorylation and activation of the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs. Obesity is typically associated with chronically elevated leptin levels and a decreased ability of LEPRb to activate intracellular signal transduction pathways (leptin resistance. Here we have studied the roles of the intracellular tyrosine residues in the negative feedback regulation of LEPRb-signaling under chronic leptin stimulation. Results Mutational analysis showed that the presence of either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines rendered LEPRb resistant to feedback regulation. Overexpression and RNA interference-mediated downregulation of suppressor of cytokine signaling 3 (SOCS3 revealed that both Tyr985 and Tyr1077 were capable of supporting the negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb complex after 2 h of leptin stimulation was not accompanied by the dephosphorylation or degradation of LEPRb or the receptor-associated JAK molecule, but depended on Tyr985 and/or Tyr1077. Conclusions Both Tyr985 and Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in the intracellular domain of LEPRb.

  10. Leptin and body mass index in polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Nasrin Jalilian

    2016-01-01

    Full Text Available Objective: Polycystic ovary syndrome (PCOS is a common endocrine disorder associated with obesity. Human and animal studies showed a direct relationship between leptin level and obesity, however, results from different studies were mixed. This study investigated the status of leptin level in PCOS and its relationship with body mass index (BMI in a group of Iranian women with PCOS. Methods: In this cross-sectional study, 40 women with PCOS and 36 healthy women were assigned to experimental and control groups, respectively. Those in the PCOS group were not prescribed any medications for 3 months prior to the study. Fasting blood samples were then collected during the 2nd or 3rd day of menstruation for laboratory measurement of serum total leptin, blood glucose (fasting blood sugar, serum insulin, follicle-stimulating hormone, and luteinizing hormone (LH. Results: Mean BMI of the PCOS and control groups were 26.62 ± 4.03 kg/m2 and 23.52 ± 2.52 kg/m2, respectively (P = 0.006. The mean total leptin in the PCO group was also 10.69 ± 5.37 ng/mL and 5.73 ± 2.36 ng/mL in the control group (P = 0.0001. A significant relationship was found between leptin level and BMI as well as LH level among women with PCOS (P 0.05. Conclusion: The results of this study indicated an increased leptin level among women with PCOS that positively associated with BMI and LH.

  11. The detection of serum leptin in peri-menopausal woman

    International Nuclear Information System (INIS)

    Wei Tao; Ma Yongxiu; He Juan

    2001-01-01

    Serum leptin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2 ) were measured by RIA in 138 peri-menopausal women in order to clear the relations between them. The results showed that serum levels of all the four circulating hormones are all changed significantly in all subgroups. Compared with the women of childbearing age group, it changed with P < 0.05; P < 0.01 respectively. All the changes indicate: As a circulating hormone, leptin plays an important role in woman's normal physiology developing process along ages

  12. Leptin, its receptor and aromatase expression in deep infiltrating endometriosis.

    Science.gov (United States)

    Gonçalves, Helder F; Zendron, Carolina; Cavalcante, Fernanda S; Aiceles, Verônica; Oliveira, Marco Aurélio P; Manaia, Jorge Henrique M; Babinski, Márcio A; Ramos, Cristiane F

    2015-08-05

    The aim of this study was to evaluate the leptin levels in the serum and peritoneal fluid (PF) and the protein expression in three different peritoneal ectopic implants in patients who underwent surgery for deep infiltrating endometriosis. All patients had been treated at the Department of Gynecology of the Pedro Ernesto University Hospital, Rio de Janeiro. The study group consisted of 15 patients who underwent surgery for adnexal masses and infertility, while the control group consisted of ten women who underwent surgery for tubal ligation. Peritoneal fluid and samples tissues were collected during surgery. Serum samples were obtained before anesthesia. In this study, the leptin levels in the serum and peritoneal fluid (PF) were evaluated by ELISA. The protein expression of leptin and its receptors (ObR) and aromatase enzyme were evaluated by Western blot analysis of the intestine, uterosacral ligament and vaginal septum in the ectopic implants. The t-test and one-way ANOVA with Holm-Sìdak post-test were used, and p endometriosis = 19.2 ng/mL ± 1.84, p endometriosis = 7.71 ng/mL ± 0.59, p = 0.18). Comparing women with and without ovarian implants, the leptin levels in both the serum and PF were significantly higher in women without ovarian implants (serum: with ovarian implant = 15.85 ± 1.99; without ovarian implant = 23.14 ± 2.60; ng/mL, p = 0.04; PF: with ovarian implant = 4.28 ± 1.30; without ovarian implant = 11.18 ± 2.98;ng/mL, p = 0.048). The leptin, ObR and aromatase protein expression levels were increased in lesions in the vaginal septum and were decreased in the intestine lesions. This study reports several interesting associations between the leptin levels in serum, peritoneal fluid, and tissue samples and the localization of the ectopic endometrium. Although this study does not provide a clear picture of the role of leptin in the development and progression of peritoneal implants

  13. Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program

    NARCIS (Netherlands)

    Murer, S.B.; Knopfli, B.H.; Aeberli, I.; Jung, A.; Wildhaber, J.; Wildhaber-Brooks, J.; Zimmermann, M.B.

    2011-01-01

    Background: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic

  14. The association between leptin and depressive symptoms is modulated by abdominal adiposity

    Science.gov (United States)

    Milaneschi, Yuri; Sutin, Angelina R; Terracciano, Antonio; Canepa, Marco; Gravenstein, Kristofer S; Egan, Josephine M; Vogelzangs, Nicole; Guralnik, Jack M; Bandinelli, Stefania; Penninx, Brenda WJH; Ferrucci, Luigi

    2014-01-01

    Background Evidence for a role of leptin in depression is limited and conflicting. Inconclusive findings may be explained by the complex effect of obesity on leptin signaling. In particular, both hyperleptinemia due to leptin resistance in obese persons as well as low leptin in lean persons can imply that low leptin biological signaling is associated with an increased risk of significant depressive symptoms. We tested whether the relationship between leptin and depressive symptoms is modulated by abdominal adiposity in two population-based studies. Methods Data were from 851 participants (65–94 years) of the InCHIANTI Study and 1,064 (26–93 years) of the Baltimore Longitudinal Study of Aging (BLSA). Plasma concentrations of leptin, waist circumference and depressive symptoms via the Center for Epidemiological Studies-Depression scale (CES-D) were assessed. In longitudinal InCHIANTI analyses onset of depressed mood (CES-D≥20) was evaluated over a 9-year follow-up. Results In pooled cross-sectional analyses the interaction between leptin and waist circumference was significantly associated with CES-D scores ((log)leptin-by-waist interaction p=0.01). Also in longitudinal analyses, the (log)leptin-by-waist interaction term significantly (p=0.04) predicted depressed mood onset over time; depressed mood risk was especially increased for high levels of both leptin and waist circumference. Conclusions The present findings suggest that low leptin signaling rather than low leptin concentration is a risk factor for depression. Future studies should develop proxy measures of leptin signaling by combining information on abdominal adiposity and leptin level to be used for clinical and research applications. PMID:24636496

  15. Clinical significance of changes of serum leptin and insulin levels in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chen Zhaojun; Zhang Lahong; Gao Ying; Ren Xiaohua

    2007-01-01

    Objective: To explore the relationship between the serum leptin, insulin levels and development of polycystic ovary syndrome (PCOS). Methods: Serum leptin and insulin levels (with RIA) were determined in 34 patients with PCOS and 30 controls. Results: The serum leptin and insulin levels in the 34 PCOS patients were significantly higher than those in controls (P<0. 01), and those in obese patients (n=22) were significantly higher than those in non-obese ones (n=12) too(P<0.01). Conclusion: Changes of serum leptin and insulin levels were closely related to the development of PCOS and leptin might be used as a diagnostic indicator for PCOS. (authors)

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

    Science.gov (United States)

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

    2015-08-01

    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. 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. 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). Serum leptin (P nutritional factors in hemodialysis patients.

  17. Molecular cloning, characterization and evolutionary analysis of leptin gene in Chinese giant salamander, Andrias davidianus

    Directory of Open Access Journals (Sweden)

    Tian Hai-feng

    2017-11-01

    Full Text Available Leptin is an important hormone possessing diverse physiological roles in mammals and teleosts. However, it has been characterized only in a few amphibian species, and its evolutions are still under debate. Here, the full length of the leptin (Adlep cDNA of Chinese giant salamander (Andrias davidianus, an early diverging amphibian species, is characterized and according to the results of the primary sequence analysis, tertiary structure reconstruction and phylogenetic analysis is confirmed to be an ortholog of mammalian leptin. An intron was identified between the coding exons of A. davidianus leptin, which indicated that the leptin is present in the salamander genome and contains a conserved gene structure in vertebrates. Adlep is widely distributed but expression levels vary among different tissues, with highest expression levels in the muscle. Additionally, the leptin receptor and other genes were mapped to three known leptin signaling pathways, suggesting that the leptin signaling pathways are present in A. davidianus. Phylogenetic topology of leptins are consistent with the generally accepted evolutionary relationships of vertebrates, and multiple leptin members found in teleosts seem to be obtained through a Cluopeocephala-specific gene duplication event. Our results will lay a foundation for further investigations into the physiological roles of leptin in A. davidianus.

  18. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers.

    Science.gov (United States)

    Vernooy, J H J; Drummen, N E A; van Suylen, R J; Cloots, R H E; Möller, G M; Bracke, K R; Zuyderduyn, S; Dentener, M A; Brusselle, G G; Hiemstra, P S; Wouters, E F M

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory reaction of the lungs involving activation of epithelial cells. Leptin is a pleiotropic cytokine important in the regulation of immune responses via its functional receptor Ob-Rb. This study was undertaken to test the hypothesis that severe COPD is associated with increased leptin expression in epithelial cells. Immunohistochemistry for leptin was performed on peripheral lung specimens from 20 patients with COPD (GOLD stage 4), 14 asymptomatic ex-smokers and 13 never smokers. Leptin and Ob-Rb mRNA expression were determined by rtPCR in cultured primary bronchial epithelial cells and primary type II pneumocytes. NCI-H292 and A549 cell lines were used to study functional activation of leptin signalling. Leptin immunoreactivity in lung tissue was observed in bronchial epithelial cells, type II pneumocytes, macrophages (tissue/alveolar) and interstitial lymphocytic infiltrates. rtPCR analysis confirmed pulmonary leptin and Ob-Rb mRNA expression in primary bronchial epithelial cells and pneumocytes. Leptin-expressing bronchial epithelial cells and alveolar macrophages were markedly higher in patients with severe COPD and ex-smokers than in never smokers (pleptin and Ob-Rb (pLeptin induced phosphorylation of STAT3 in both NCI-H292 and A549 cells. Leptin expression is increased in bronchial epithelial cells and alveolar macrophages of ex-smokers with or without severe COPD compared with never smokers. A functional leptin signalling pathway is present in lung epithelial cells.

  19. Fasting and postprandial levels of ghrelin, leptin and insulin in lean, obese and anorexic subjects

    Science.gov (United States)

    Krauss, Hanna; Gibas-Dorna, Magdalena; Kupsz, Justyna; Piątek, Małgorzata; Piątek, Jacek

    2013-01-01

    Introduction Ghrelin, leptin and insulin are involved in neurohormonal regulation of energetic homeostasis. Aim We investigated the correlation between nutritional status and plasma levels of leptin, ghrelin and insulin in lean, obese and anorexic subjects. Material and methods Nineteen obese and 18 anorexic adults were enrolled in the study. Seventeen adults with normal body mass index (BMI) served as controls. Blood samples were taken twice: before breakfast and 2 h after breakfast. Fasting and postprandial ghrelin, leptin and insulin were examined. The following correlations were estimated: between BMI and basal level of tested hormones, between insulin and ghrelin, and between insulin and leptin. The threshold level of significance was p ≤ 0.05 for all calculations. Results Basal insulin level was lowest in anorexic patients and greatest in obese subjects. Fasting plasma ghrelin was lower in obesity and higher in anorexia as compared with the controls. Comparing with controls, fasting leptin levels were higher in obese and lower in anorexic subjects. There was positive correlation between BMI and basal leptin level in obesity. A significant postprandial increase was noted for insulin in all studied groups. Increased leptin and decreased ghrelin levels were detected 2 h after a meal in the control group. In obese patients, postprandial leptin was lower than before food intake, and fasting leptin showed positive correlation with basal insulin level. Conclusions Basal plasma ghrelin, leptin and insulin levels differ according to nutritional status. Impaired ghrelin and leptin secretion and insulin sensitivity may be involved in the pathogenesis of eating disorders. PMID:24868288

  20. Role of leptin as a link between metabolism and the immune system.

    Science.gov (United States)

    Pérez-Pérez, Antonio; Vilariño-García, Teresa; Fernández-Riejos, Patricia; Martín-González, Jenifer; Segura-Egea, Juan José; Sánchez-Margalet, Víctor

    2017-06-01

    Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

    International Nuclear Information System (INIS)

    Erkasap, N.; Ozkurt, M.; Erkasap, S.; Yasar, F.; Uzuner, K.; Ihtiyar, E.; Uslu, S.; Kara, M.; Bolluk, O.

    2013-01-01

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis

  2. The observation of leptin levels in pregnant women newborn and newborn's weight and its clinical significance

    International Nuclear Information System (INIS)

    Yuan Gengbiao; Xiao Jin; Shi Xin; Chen Xuehong

    2002-01-01

    To study the relationship of leptin quantity of placenta, amniotic fluid, umbilical blood, maternal blood and newborn's weight, leptin levels of placenta, amniotic fluid, umbilical blood and maternal blood of 59 pregnant women were detected by RIA. Results were: (1) leptin was be detected from placenta, amniotic fluid, umbilical blood and maternal blood; (2) there was an obvious difference between leptin quantities of placenta, amniotic fluid, umbilical blood and maternal blood (P < 0.01); (3) there was an obvious difference between leptin quantities of placenta, amniotic fluid, umbilical blood and maternal blood for normal pregnant women and pregnancy induced hypertension (P < 0.01); (4) there was an obvious difference between leptin quantities of maternal blood and placenta (P < 0.01). It may be of important significance to detect eh leptin quantity of amniotic fluid and maternal blood in pregnant women for predicting the weight and growth of newborns and treat pregnancy induced hypertension

  3. Changes of serum leptin and other related hormones levels in simple obese children

    International Nuclear Information System (INIS)

    Xiao Jinhua; Wang Yaping; Xu Yan; Gao Yufeng

    2001-01-01

    Objective: To measure the serum leptin concentration in simple obese children together with other four kinds of related hormones. Methods: Serum Leptin, Ins, T 3 , T 4 and GH levels were measured by radioimmunoassay in thirty-eight obese children and thirty healthy controls. Results: The levels of serum leptin, Ins and T 3 in obese group were dramatically higher than those in control group (all P 4 concentration between simple obese children and control group (P > 0.05), Serum GH levels was significantly decreased in simple obese children (P < 0.01). There was a positive correlation between serum leptin levels and lns levels (r = 0.46, P < 0.01). Conclusion: In simple obese children there were leptin resistance and endocrine metabolic disturbances, the later might be correlated with the increasing of serum leptin levels; It is suggested that Leptin resistance might play a key role in the development of obesity

  4. Does tibolone affect serum leptin levels and body weight in postmenopausal women?

    Science.gov (United States)

    Gol, Mert; Ozsener, Serdar; Sendag, Fatih; Uretmen, Sevinç; Oztekin, Kemal; Tanyalcin, Tijen; Bilgin, Onur

    2005-07-01

    Leptin has a significant role in body weight regulation and energy balance. We examined the effect of tibolone on the body weight and serum leptin levels in postmenopausal women. Twenty women (aged 43-60 years) participated in this prospective study. All women in this study protocol received 2.5 mg/day of tibolone. Absolute and body mass index (BMI)-corrected serum leptin concentrations and BMI values were measured at baseline, after 3 months, and after 6 months of the tibolone therapy. Tibolone did not affect absolute and BMI-corrected serum leptin levels, and BMI values during the treatment. A significant linear correlation between BMI values and serum leptin levels was observed (p<0.05, r=0.67). Tibolone seems not to affect serum leptin levels, body weight and BMI values of postmenopausal women. There is a significant correlation between serum leptin levels and BMI values.

  5. The plasma leptin concentration is closely associated with the body fat mass in nondiabetic uremic patients

    DEFF Research Database (Denmark)

    Clausen, P; Nielsen, P K; Olgaard, K

    1999-01-01

    filtration rate seemed to have a limited influence on the plasma leptin concentration in nondiabetic uremic subjects matched by body fat mass to controls. The plasma leptin concentration was closely associated with the body fat mass, and the leptin level might, therefore, be useful as an indicator of the fat......Plasma leptin is associated with the body mass index and, more precisely, with the body fat mass. Plasma leptin has been found to be elevated in uremic patients. This study aimed at investigating the plasma leptin concentration and associations between plasma leptin, body fat mass, and glomerular.......4 (3.1-59.5) ng/ml versus 5.4 (1.6-47.5) ng/ml (median and range in parentheses; p

  6. Serum leptin levels in pregnant women with type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Lauszus, F F; Schmitz, O; Vestergaard, H

    2001-01-01

    BACKGROUND: Leptin is an important weight regulator and during pregnancy leptin is not only synthesized in adipose tissue but also in the placenta. AIM: To examine changes in serum leptin levels in women with type 1 diabetes mellitus during pregnancy and post delivery in relation to concomitant...... changes in maternal body weight, birth weight, glycemic control, and blood pressure. METHODS: Non-fasting serum leptin from 45 women with type 1 diabetes mellitus were studied consecutively throughout pregnancy and 3 months post partum. RESULTS: Serum leptin was positively associated with HbA1c in week 18...... of serum leptin throughout pregnancy and it changed significantly differently from the women with higher blood pressure (pserum leptin levels of pregnant women with type 1 diabetes mellitus were associated with parallel changes in maternal body weight and glycemic control...

  7. Postnatal leptin promotes organ maturation and development in IUGR piglets.

    Science.gov (United States)

    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.

  8. Leptin receptor polymorphisms and lung function decline in COPD

    OpenAIRE

    Hansel, N.N.; Gao, L.; Rafaels, N.M.; Mathias, R.A.; Neptune, E.R.; Tankersley, C.; Grant, A.V.; Connett, J.; Beaty, T.H.; Wise, R.A.; Barnes, K.C.

    2009-01-01

    Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in the LEPR gene and lung function decline in COPD.

  9. Role of leptin and adiponectin in gestational diabetes mellitus: a ...

    African Journals Online (AJOL)

    One of the mechanisms underlying glucose metabolism in pregnancy are a group of substances, which includes leptin and adiponectin, produced mainly in the adipose tissue; in this paper we analyze the role of these mediators in women with GDM. This case control study was performed in 90 females (30 GDM patients ...

  10. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    2016-12-21

    Dec 21, 2016 ... showed binge-like eating with increased HPA axis activity when they were ..... brain. Many studies have reported that leptin is a stress- response hormone and its action may be related with the. HPA axis activity (Heiman et al. 1997 .... a cancer cell line, and the STAT3 target genes included ones that were ...

  11. The Effect of EPH- Gestosis on Plasma Leptin concentration | Ajayi ...

    African Journals Online (AJOL)

    Edema-proteinuria-hypertension-gestosis complex develops in late pregnancy and is usually associated with placenta hypoxia and dysfunction. Leptin, the obsess gene product, is adipocyte-derived hormone that reduces calorie intake and body fat consequently results in weight lost. Recently it had been shown to be ...

  12. BLOOD METABOLIC HORMONES AND LEPTIN IN GROWING LAMBS

    Directory of Open Access Journals (Sweden)

    Zvonko Antunović

    2010-12-01

    Full Text Available The aim of this paper is to determine the concentration of blood metabolic hormones and leptin levels in growing lambs. The research was carried out on Tsigai lambs in two periods (suckling and fattening during the winter feeding season. Lambs were suckling and ate a food mixture and alfalfa hay ad libitum, while during the fattening period they were fed only with the above mentioned mixture and alfalfa hay ad libitum. Their blood was analyzed on 35th and 75th day of age. Concentrations of minsulin, leptin and thyroid hormones were determined in the blood serum of lambs during both periods. In the blood of fattening lambs significantly higher (P0.05 insulin concentrations (1.05 and 0.54 μU/mL, were determined, compared to suckling lambs. A significant strong positive correlation between serum leptin and insulin (r = 0.85, P0.05. The concentration of thyroid hormones did not significantly differ depending on the period of measurement. These changes indicate that the measurement concentrations of metabolic hormones and leptin in blood are very important in order to understand the changes of metabolism and nutrient supply in growing lambs.

  13. Leptin, Adiponectin, and Obesity among Caucasian and Asian Women

    Directory of Open Access Journals (Sweden)

    Shannon M. Conroy

    2011-01-01

    Full Text Available Ethnic differences in adipose tissue distribution may contribute to different chronic disease risks across ethnic groups, and adipokines may mediate the risk. In a cross-sectional study, we examined ethnic differences in adipokines and inflammatory markers as related to body mass index (BMI among 183 premenopausal women with Caucasian and Asian ancestry. General linear models were used to estimate adjusted mean levels of leptin, adiponectin, interleukin-6, and C-reactive protein (CRP. Asian women had significantly lower serum levels of leptin, adiponectin, and CRP than Caucasian participants (P≤.01 across all levels of BMI. Among overweight and obese women, Asians showed a stronger association of CRP with leptin (β=1.34 versus β=0.64 and with adiponectin (β=−0.95 versus β=−0.75 than Caucasians. Compared to Caucasians of similar BMI, Asians may experience a higher chronic disease risk due to lower levels of adiponectin despite their lower levels of leptin.

  14. Physiology and genetics of leptin in periparturient dairy cows

    NARCIS (Netherlands)

    Liefers, S.C.

    2004-01-01

    In dairy cattle, the increase in milk yield has been accompanied by a decrease in fertility and a more negative energy balance. As the hormone leptin is involved in regulation of nutritional status and reproductive function (Chapter 2) this is an

  15. Plasma leptin levels in healthy children and adolescents

    DEFF Research Database (Denmark)

    Blum, W F; Englaro, P; Hanitsch, S

    1997-01-01

    Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine...... increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin...... levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further...

  16. Relation between obesity, lipid profile, leptin and atopic disorders in ...

    African Journals Online (AJOL)

    Background: Obesity has become a disease of great importance affecting children and adolescents. Obesity can cause atopy or inflammation, where there are some common factors that predispose to both obesity and atopy. Objective: To study the factors contributing to allergic disorders in obese children, the role of leptin ...

  17. Plasma leptin levels in healthy children and adolescents

    DEFF Research Database (Denmark)

    Blum, W F; Englaro, P; Hanitsch, S

    1997-01-01

    Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine...

  18. Serum Leptin Is a Biomarker of Malnutrition in Decompensated Cirrhosis

    Science.gov (United States)

    Rachakonda, Vikrant; Borhani, Amir A.; Dunn, Michael A.; Andrzejewski, Margaret; Martin, Kelly; Behari, Jaideep

    2016-01-01

    Background and Aims Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition. Design In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference malnutrition. Results Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition. Conclusions Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease. PMID:27583675

  19. Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate ...

    African Journals Online (AJOL)

    HP

    plumbagin treatment in HSC-LX2 (p < 0.01). p-ERK1/2 expression markedly decreased in plumbagin-treated. HSCs (p < 0.01). Plumbagin significantly increased MMP-1 expression in leptin-treated HSCs (p < 0.01). Conclusion: Plumbagin has an anti-fibrotic effect and may decrease the protein expressions of components.

  20. Adrenomedullin and leptin levels in diabetic retinopathy and retinal diseases.

    Science.gov (United States)

    Er, Hamdi; Doğanay, Selim; Ozerol, Elif; Yürekli, Muhittin

    2005-01-01

    Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human. In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m2)] was calculated for each group. The Mann-Whitney U test was used for statistics. The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9+/-7.1 pmol/l) were significantly higher (pdiabetic retinopathy than in those without diabetes (1.83+/-0.5 ng/ml). Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases. Copyright (c) 2005 S. Karger AG, Basel.

  1. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome ...

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  2. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  3. Expression of Leptin (Ob Gene Product) in Reproductive System ...

    African Journals Online (AJOL)

    Purpose: To determine serum leptin and its ob mRNA expression both in the PCOS and non-PCOS ovary, endometrium and adipose tissue in normal or polycystic ovary syndrome (PCOS) in South Indian population. PCOS (Polycystic Ovary Syndrome) and non-PCOS subject's endometrium, ovary and adipose tissue were ...

  4. The association between leptin, body composition and physical ...

    African Journals Online (AJOL)

    This study investigated the association between leptin, body composition and physical fitness in black adolescents from two selected schools in Ikageng, in the North West Province of South Africa. Baseline measurements were obtained from 124 boys and 148 girls between the ages of 13 and 20 years, which participated in ...

  5. Allelic polymorphism of Makoei sheep leptin gene identified by ...

    African Journals Online (AJOL)

    use

    2011-12-05

    Dec 5, 2011 ... intake, energy expenditure and whole-body energy balance in animals. In the present study, the polymorphism of the leptin gene (LEP) of Makoei sheep was investigated by polymerase chain reaction and single strand conformation polymorphism technique (PCR–SSCP). Genomic DNA was extracted.

  6. Leptin responses to bovine interferon- α and insulin in cattle

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology ... IFN- α injection produced a rapid increase in glucose and insulin levels but leptin levels did not show any alteration after the injection. ... Insulin levels rapidly increased in the blood and consequently a significant decrease in blood glucose level was recorded.

  7. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    Furthermore, HCT-116 colon cancer cells were used to elucidate the effect of PI3K/Akt/. mTOR signalling pathway on the leptin's regulation on colon cancer. 2. Materials and ... prior knowledge of the patients' clinical data using Olympus. CX42 microscope ..... and clinicopathologic characteristics of colorectal cancer.

  8. Leptin and Anthropometric Indices in Adolescents with Sickle Cell ...

    African Journals Online (AJOL)

    Background: Leptin is a peptide hormone secreted by adipocytes and acts to promote weight loss by decreasing food intake, increasing metabolic rate and energy expenditure. In sickle cell anaemia (SCA), poor growth and nutritional status are common clinical features. Adolescence is a period of rapid growth; in sickle cell ...

  9. Leptin, Leptin Soluble Receptor, and the Free Leptin Index following a Diet and Physical Activity Lifestyle Intervention in Obese Males and Females

    Directory of Open Access Journals (Sweden)

    Jeffrey E. Herrick

    2016-01-01

    Full Text Available Leptin (LEP is associated with appetite regulation and metabolism. Concentration is linear with adiposity, suggesting LEP resistance. LEP circulates freely and bound with its soluble receptor (sOB-r; the ratio is the free leptin index (FLI, an index of leptin resistance; lower FLI suggests reduced biological action. Purpose. The aim was to determine the effect of changes in adipose tissue distribution on LEP, sOB-r, and FLI following 6 months (6 M of a diet/exercise weight loss program (WLP. In addition, we aim to identify predictors of the FLI. Methods. 6 M WLP consisted of diet/lifestyle interventions following ADA guidelines. Body composition was assessed by DXA. LEP and sOB-r analysis were done via ELISA. Results. 10 adults completed the WLP. Significant reductions were seen in total fat percentage (% fat, nontrunk fat, (NTF, and trunk fat (TF from base to 3 m and 6 M (p≤0.05. The FLI were reduced at 3 M and 6 M for males and 6 M for females. Total body fat and body weight predicted the FLI in both sexes. Conclusions. LEP and FLI reductions following 6 M of WLP were achieved independent of sOB-r changes. We also demonstrate that the FLI can be predicted noninvasively through total fat mass and body weight in kilograms.

  10. Leptin levels in different forms of Chagas' disease

    Directory of Open Access Journals (Sweden)

    F. Fernandes

    2007-12-01

    Full Text Available Leptin is produced primarily by adipocytes. Although originally associated with the central regulation of satiety and energy metabolism, increasing evidence indicates that leptin may be an important mediator in cardiovascular pathophysiology. The aim of the present study was to investigate plasma leptin levels in patient with Chagas' heart disease and their relation to different forms of the disease. We studied 52 chagasic patients and 30 controls matched for age and body mass index. All subjects underwent anthropometric, leptin and N-terminal pro-brain natriuretic peptide (NT-proBNP measurements and were evaluated by echocardiography, 12-lead electrocardiogram (ECG, and chest X-ray. All patients had fasting blood samples taken between 8:00 and 9:00 am. Chagasic patients were divided into 3 groups: group I (indeterminate form, IF group consisted of 24 subjects with 2 positive serologic reactions for Chagas' disease and no cardiac involvement as evaluated by chest X-rays, ECG and two-dimensional echocardiography; group II (showing ECG abnormalities and normal left ventricular systolic function, ECG group consisted of 14 patients; group III consisted of 14 patients with congestive heart failure (CHF group and left ventricular dysfunction. Serum leptin levels were significantly lower (P < 0.001 in the CHF group (1.4 ± 0.8 ng/mL when compared to the IF group (5.3 ± 5.3 ng/mL, ECG group (9.7 ± 10.7 ng/mL, and control group (8.1 ± 7.8 ng/mL. NT-proBNP levels were significantly higher (P < 0.001 in the CHF group (831.8 ± 800.1 pg/mL when compared to the IF group (53.2 ± 33.3 pg/mL, ECG group (83.3 ± 57.4 pg/mL, and control group (32 ± 22.7 pg/mL. Patients with Chagas' disease and an advanced stage of CHF have high levels of NT-ProBNP andlow plasma levels of leptin. One or more leptin-suppressing mechanisms may operate in chagasic patients.

  11. Regulation of chick bone growth by leptin and catecholamines.

    Science.gov (United States)

    Mauro, L J; Wenzel, S J; Sindberg, G M

    2010-04-01

    Leptin and the sympathetic nervous system have a unique role in linking nutritional status to skeletal metabolism in mammals. Such a regulatory mechanism has not been identified in birds but would be beneficial to signal information about energy reserves to an organ system essential for locomotion, reproduction, and survival. To explore this potential role of leptin and the sympathetic nervous system in birds, an ex vivo chick tibiotarsal model was used to test the effects of leptin and sympathetic activity on longitudinal bone growth and the expression of chondrocyte markers. Reverse transcription-PCR analysis revealed the expression of chicken leptin receptor mRNA as well as both alpha-adrenergic (alpha1A, alpha2A, alpha2B, alpha2C) and beta adrenergic (beta1, beta2) receptor subtype mRNA in the whole bone. Incubation with norepinephrine (NE; 0, 10, or 100 microM for 4 d) caused a significant increase in distal condyle length as compared with vehicle-treated, contralateral tibiotarsi. In contrast, no change in condyle length was detected after leptin treatment (0 or 10 nM or 1 microM for 4 d). Analysis of cell proliferation by bromodeoxyuridine incorporation revealed no increase in bromodeoxyuridine-positive cells in the condyles in response to leptin or NE treatments. Real-time PCR analysis showed that NE enhanced type X collagen mRNA expression, a marker of mature hypertrophic chondrocytes, with no effect on type II collagen mRNA, the matrix protein secreted by proliferating chondrocytes. Leptin treatment had no effect on the expression of either matrix protein. Treatment with agonists specific for alpha- or beta-adrenergic receptors indicates that the activation of alpha-adrenergic receptors is most likely responsible for the sympathetic effect on type X collagen gene expression. These results suggest that NE and other sympathetic agonists have positive effects on bone elongation and the changes in critical genes associated with this process. These

  12. Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation.

    Science.gov (United States)

    Lourenço, Elaine V; Liu, Aijing; Matarese, Giuseppe; La Cava, Antonio

    2016-09-20

    Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptin-sufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.

  13. Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes.

    Science.gov (United States)

    Stjernholm, Theresa; Ommen, Pernille; Langkilde, Ane; Johansen, Claus; Iversen, Lars; Rosada, Cecilia; Stenderup, Karin

    2017-04-01

    Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum leptin levels are elevated in obese individuals and correlate positively with body mass index (BMI). Interestingly, serum leptin levels are also elevated in patients with psoriasis and correlate positively with disease severity. Psoriasis is associated with obesity; patients with psoriasis have a higher incidence of obesity, and obese individuals have a higher risk of developing psoriasis. Additionally, obese patients with psoriasis experience a more severe degree of psoriasis. In this study, we hypothesised that leptin may link psoriasis and obesity and plays an aggravating role in psoriasis. To investigate leptin's role in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis-like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and investigated the effect on proliferation and expression of pro-inflammatory proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in dorsal skin and inflammation in ear skin, as measured by ear thickness, were attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression levels, as well as increased epidermal thickness, were significantly less induced. In vitro, the effect of leptin stimulation on human keratinocytes demonstrated increased proliferation and induced secretion of several pro-inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse model, and leptin stimulation induced a pro-inflammatory phenotype in human keratinocytes, thus, supporting an aggravating role of leptin in psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Serum Leptin Levels in Asthma, COPD and Bronchiectasis

    Directory of Open Access Journals (Sweden)

    Ercan Kurtipek

    2016-01-01

    Full Text Available Aim: The aim of the present study is to compare body mass indexes (BMI and serum leptin levels of most frequently observed three chronic airway diseases; namely, Asthma, Chronic Obstructive Pulmonary Disease (COPD and bronchiectasis. Material and Method: The study included a total of 216 people, 78 asthma, 67 COPD, and 37 bronchiectasis patients who were in stable period and 34 healthy individuals all aged above 18. Control group consisted of non-smokers and non-corticosteroid users. Of all the participants, the blood samples were taken in order to determine serum leptin levels and BMI were calculated, and pulmonary function tests measured at rest. Results: The BMI levels of all the groups was above >25 kg/m2. There were no statistical differences between the control and patient groups with regard to BMI (p>0.05. Comparing patient groups, the BMI of asthma patients was higher than those with COPD and bronchiectasis (29.84±6.46, 25.78±4.96, 27.64±5.19, p=0.0001, p=0.20. FEV1 results of COPD patients were lower than those with asthma and bronchiectasis (63.25±19.26, 76.73±20.35, 72.75±20.17 and p=0.0001, p=0.06. Serum leptin levels of asthma patients were higher than the COPD, bronchiectasis patients, as well as that of the control group (12.36±11.16 ng/ml, 3.35±4.71 ng/ml, 8.49±7.85 ng/ml and 5.21±6.83 ng/ml, p=0.0001, p=0.09 and p=0.0001, respectively. Serum leptin level of COPD patients was lower than control group, but it was not statistically significant (p=0.71. Serum leptin levels of the patients with bronchiectasis were higher than healthy control group members; yet , not statistical significant (p=0.34. However serum leptin levels of the patients with bronchiectasis were higher than the patient COPD groups and this was statisticaly significant (p=0.01. Istatistically significant different emerge on comparing serum leptin levels and BMI of the asthma, COPD and bronchiectasis patients in the Lineear regression analysis made (beta

  15. [Preliminary investigation of effect of serum leptin on nutritional state of COPD patients].

    Science.gov (United States)

    Yuan, Y; Wang, Z; Liu, C

    2000-05-01

    To explore the significance of serum leptin and TNF-alpha in malnutrition of COPD. Serum leptin and TNF-alpha concentrations were measured by radioimmunoassay. Body mass index (BMI), percent normal body weight (NW%), triceps skin-fold thickness (TSF), subscapular skin-fold thickness (SSF), mid-upper arm circumference (MAC), serum albumin (ALB) and total lymphocytes count (LYM) were determined in 31 patients with COPD and in 11 healthy controls. The correlation between leptin and nutritional parameters was analysed. (1) Serum leptin concentrations (3.0 +/- 2.5) micrograms/L in 42 subjects were significantly correlated with BMI, NW%, TSF, SSF and MAC (P leptin concentrations were significantly correlated with BMI in both malnourished patients with COPD and non-malnourished patients (P leptin level was significantly lower in malnourished group (1.3 +/- 1.0) micrograms/L than in non-malnourished group (4.5 +/- 2.6) micrograms/L, (P leptin level and BMI between non-malnourished group and healthy group were not significant. (3) Serum TNF-alpha level was significantly higher in COPD group (1.8 +/- 0.3) micrograms/L than in healthy group (1.0 +/- 0.5) microgram/L (P leptin levels didn't significantly correlate with TNF-alpha levels in COPD patients. Serum leptin levels correlate with nutritional parameters in COPD patients and leptin may contribute to the malnutrition in COPD patients.

  16. Effect of Technological Treatments on Human-Like Leptin Level in Bovine Milk for Human Consumption

    Directory of Open Access Journals (Sweden)

    Damiano Magistrelli

    2014-07-01

    Full Text Available In this experiment, raw milk and commercially available full-cream UHT milk, semi-skimmed UHT milk, skimmed UHT milk, full-cream pasteurized milk, semi-skimmed pasteurized milk and infant formulas for babies between 6 and 12 months of age were analyzed by RIA, with a method using an antibody directed against human leptin and human leptin as reference standard. Raw milk and full-cream UHT milk did not differ for human-like leptin. Leptin content of full-cream pasteurized milk was not different to that of full-cream UHT milk, but it was 14% lower (p < 0.05 than that observed in raw milk. Human-like leptin level of semi-skimmed UHT milk was not different to that of semi-skimmed pasteurized milk, but it was 30% lower (p < 0.0001 than those of full-cream UHT and full-cream pasteurized milks. In skimmed UHT milk, leptin was 40% lower (p < 0.0001 than in full-cream UHT milk. Leptin was correlated (p < 0.001 with lipid content. Leptin level of infant formulas was not different to that of skimmed milks. Results suggest that the heat treatment (pasteurization or UHT is not a modifier of human-like leptin content of edible commercial bovine milks, whereas the skimming process significantly reduces milk leptin level.

  17. Serum Leptin Concentrations during the Menstrual Cycle in Iranian Healthy Women

    Directory of Open Access Journals (Sweden)

    Nahid Einollahi

    2010-09-01

    Full Text Available "nLeptin, a circulating 16-kd polypeptide consisting of 167 amino acids, appears to be involved in the body weight homeostasis. Moreover leptin plays an important role for the reproductive system, early embryogenesis, and fat metabolism during pregnancy and puberty. Significant correlations have been found between leptin and sexual hormones, which is a cytokine and has hormonal properties. The aim of this study was to determine serum leptin levels during the menstrual cycle, and the association between serum leptin and reproductive hormones in young, healthy Iranian women. 42 healthy women volunteered for the study. They all had regular menstrual cycles, with cycle length varying between 26 and 32 days. None of them used oral contraceptives. All were of normal weight, with body mass index ( BMI < 25 Kg/m2. Fasting blood samples were collected during the follicular phase, mid cycle and luteal phase of the menstrual cycle. FSH and LH were measured with coated tube immunoradiometric assay. Estrogen and progesterone were measured using antibody -coated tubes. Serum Leptin concentration were measured by Leptin (sandwich ELISA. In menstruating women, serum leptin increased from 13.15+/-1.60 ng/ml in the early follicular phase to 16.57+/-1.68 ng/ml (P<0.01 at the luteal phase. Serum leptin concentration negatively correlated with LH and progesterone (P<0.05. Mean serum leptin levels correlated with body mass index (BMI (r =0.78, P<0.001.

  18. Effects of sex steroid hormones and menopause on serum leptin concentrations.

    Science.gov (United States)

    Di Carlo, C; Tommaselli, G A; Nappi, C

    2002-12-01

    Leptin is a protein secreted by adipocytes; its circulating levels are correlated to fat mass and it acts on the hypothalamic centers regulating body weight. Leptin may also play an important role in regulating reproductive function. Indeed, ob/ob mice, lacking leptin due to a genetic mutation, are obese and infertile; administration of recombinant leptin to these animals reduces body weight and restores fertility. A sexual dimorphism in serum leptin levels has also been observed, with higher concentrations in women. Studies in vitro seem to indicate that estrogens stimulate leptin secretion, while in vivo studies are extremely discordant. In humans, several studies showed increased, unmodified and decreased leptin levels after the menopause. Furthermore, hormonal replacement therapy (HRT) after the menopause was reported to result in unmodified, increased or decreased leptin levels. It is likely that the effects of postmenopausal hypoestrogenism on leptin levels are masked by the postmenopausal changes in body composition. Indeed, after menopause, there is an increase in body weight, body mass index (BMI) and fat mass with a centralization of fat distribution. Administration of HRT may stop these changes and even restore a premenopausal pattern, leading then to decreased leptin levels.

  19. Seminal plasma leptin and spermatozoon apoptosis in patients with varicocele and leucocytospermia.

    Science.gov (United States)

    Wang, H; Lv, Y; Hu, K; Feng, T; Jin, Y; Wang, Y; Huang, Y; Chen, B

    2015-08-01

    Excessive apoptotic spermatozoon death is associated with male infertility. Leptin regulates apoptosis in several cell types. We prospectively investigated if seminal plasma leptin mediates spermatozoon apoptosis in 74 varicocele (VC) patients and 70 leucocytospermia patients. Spermatozoa from 40 normospermic men were used as controls. Routine semen analysis, spermatozoon apoptosis rate, seminal plasma leptin, reactive oxygen species (ROS) and tumour necrosis factor-alpha (TNF-α) levels were measured. In VC and leucocytospermia patients, seminal plasma leptin levels and spermatozoon apoptosis rates were significantly higher compared with controls. In the VC group, seminal plasma ROS levels were significantly higher compared with controls; there were no significant differences in TNF-α levels. In the leucocytospermia group, both ROS and TNF-α levels were significantly higher compared with controls. In both the VC and leucocytospermia groups, there was a significant positive correlation between the spermatozoon apoptosis rate and leptin levels and ROS and leptin levels. There was a significant correlation between leptin and TNF-α levels in the leucocytospermia group. Seminal plasma leptin levels correlate significantly with spermatozoon apoptosis rate, and leptin may be a spermatozoon pro-apoptotic factors. The generation of ROS is a possible mechanism. Leptin may induce apoptosis via TNF-α in leucocytospermia patients. © 2014 Blackwell Verlag GmbH.

  20. Rhythmic leptin is required for weight gain from circadian desynchronized feeding in the mouse.

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    Deanna Marie Arble

    Full Text Available The neuroendocrine and metabolic effects of leptin have been extensively researched since the discovery, and the later identification, of the leptin gene mutated within the ob/ob mouse. Leptin is required for optimal health in a number of physiological systems (e.g. fertility, bone density, body weight regulation. Despite the extensive leptin literature and many observations of leptin's cyclical pattern over the 24-hour day, few studies have specifically examined how the circadian rhythm of leptin may be essential to leptin signaling and health. Here we present data indicating that a rhythmic leptin profile (e.g. 1 peak every 24 hours leads to excessive weight gain during desynchronized feeding whereas non-rhythmic leptin provided in a continuous manner does not lead to excessive body weight gain under similar feeding conditions. This study suggests that feeding time can interact with leptin's endogenous rhythm to influence metabolic signals, specifically leading to excessive body weight gains during 'wrongly' timed feeding.

  1. Beneficial Effect of Leptin on Spatial Learning and Memory in Streptozotocin-Induced Diabetic Rats

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    Mohsen Ghasemi

    2016-02-01

    Full Text Available Background: Diabetes mellitus is a chronic disease which may be accompanied by cognitive impairments. The expression of the obesity gene (ob is decreased in insulin-deficient diabetic animals and increased after the administration of insulin or leptin. Plasma leptin levels are reduced in the streptozotocin (STZ-induced diabetic rats. Therefore, the deleterious effects of diabetes on memory may be due to the reduction of leptin. Aims: Investigate the effect of subcutaneous injection of leptin on spatial learning and memory in STZ-induced diabetic rats. Study Design: Animal experimentation. Methods: The rats were divided into three groups: 1- control, 2- diabetic, and 3- diabetic-leptin. Diabetes was induced in groups 2 and 3 by STZ injection (55 mg/kg intraperitoneally (i.p. The animals received leptin (0.1 mg/kg or saline subcutaneously (s.c for 10 days before behavioral studies. Then, they were examined in the Morris water maze over 3 blocks after 3 days of the last injection of leptin. Results: The travelled path length and time spent to reach the platform significantly increased in the diabetic group (p<0.001 and decreased with leptin treatment (p<0.01 & p<0.001 respectively; also, a significant increase in path length and time was observed between the diabetic-leptin group and the diabetic group (p<0.01, p<0.001, respectively in the probe test. Conclusion: Leptin can exert positive effects on memory impairments in diabetic rats.

  2. Maternal leptin and body composition in the first trimester of pregnancy.

    LENUS (Irish Health Repository)

    Fattah, Chro

    2012-02-01

    BACKGROUND: Leptin is produced mainly by adipocytes. Levels are increased in women with obesity and during pregnancy. Increased levels are also associated with pregnancy complications such as, pre-eclampsia and gestational diabetes mellitus. OBJECTIVE: We studied what component of body composition correlated best with maternal leptin in the first trimester of pregnancy and, whether maternal leptin correlated better with visceral fat rather than fat distributed elsewhere. SUBJECTS AND METHODS: Women were recruited in the first trimester. Maternal adiposity was measured using body mass index and advanced bioelectrical impedance analysis. Maternal leptin was measured using an enzyme-linked immunosorbent assay technique. RESULTS: Of the 100 subjects studied, the mean leptin concentration was 37.7 ng\\/ml (range: 2.1-132.8). Leptin levels did not correlate with gestational age in the first trimester, maternal age, parity or birth weight. Serum leptin correlated positively with maternal weight and body mass index, and with the different parameters of body composition. On multiple regression analysis, serum leptin correlated with visceral fat but not fat distributed elsewhere. CONCLUSIONS: Visceral fat is the main determinant of circulating maternal leptin in the first trimester of pregnancy. This raises the possibility that maternal leptin in early pregnancy may be a marker for the development of metabolic syndrome, including diabetes mellitus.

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

    Science.gov (United States)

    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.

  4. Functional evolution of leptin of Ochotona curzoniae in adaptive thermogenesis driven by cold environmental stress.

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    Jie Yang

    Full Text Available BACKGROUND: Environmental stress can accelerate the directional selection and evolutionary rate of specific stress-response proteins to bring about new or altered functions, enhancing an organism's fitness to challenging environments. Plateau pika (Ochotona curzoniae, an endemic and keystone species on Qinghai-Tibetan Plateau, is a high hypoxia and low temperature tolerant mammal with high resting metabolic rate and non-shivering thermogenesis to cope in this harsh plateau environment. Leptin is a key hormone related to how these animals regulate energy homeostasis. Previous molecular evolutionary analysis helped to generate the hypothesis that adaptive evolution of plateau pika leptin may be driven by cold stress. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis, recombinant pika leptin was first purified. The thermogenic characteristics of C57BL/6J mice injected with pika leptin under warm (23±1°C and cold (5±1°C acclimation is investigated. Expression levels of genes regulating adaptive thermogenesis in brown adipose tissue and the hypothalamus are compared between pika leptin and human leptin treatment, suggesting that pika leptin has adaptively and functionally evolved. Our results show that pika leptin regulates energy homeostasis via reduced food intake and increased energy expenditure under both warm and cold conditions. Compared with human leptin, pika leptin demonstrates a superior induced capacity for adaptive thermogenesis, which is reflected in a more enhanced β-oxidation, mitochondrial biogenesis and heat production. Moreover, leptin treatment combined with cold stimulation has a significant synergistic effect on adaptive thermogenesis, more so than is observed with a single cold exposure or single leptin treatment. CONCLUSIONS/SIGNIFICANCE: These findings support the hypothesis that cold stress has driven the functional evolution of plateau pika leptin as an ecological adaptation to the Qinghai-Tibetan Plateau.

  5. Interleukin-17A increases leptin production in human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Noh, Minsoo

    2012-03-01

    Lineage commitment of human bone marrow mesenchymal stem cells (hBM-MSCs) to adipocytes or osteoblasts has been suggested as a model system to study the relationship between type II diabetes and abnormal bone metabolism. Leptin and IL-17A inhibit adipogenesis whereas they promote osteogenesis in MSCs. Due to pathophysiologic roles of IL-17A in human metabolic diseases and bone metabolism, it was evaluated whether IL-17A-dependent inverse regulation on adipogenesis and osteogenesis was related to endogenous leptin production in hBM-MSCs. In the analysis of adiponectin and leptin secretion profiles of hBM-MSCs in response to various combinations of differentiation inducing factors, it was found that dexamethasone, a common molecule used for both adipogenesis and osteogenesis, increased leptin production in hBM-MSCs. Importantly, the level of leptin production during osteogenesis in hBM-MSCs was higher than that during adipogenesis, implicating a significant leptin production in extra-adipose tissues. IL-17A increased leptin production in hBM-MSCs and also under the condition of osteogenesis. In spite of direct inhibition on adipogenesis, IL-17A up-regulated leptin production in hBM-MSC-derived adipocytes. Anti-leptin antibody treatment partially antagonized the IL-17A dependent inhibition of adipogenesis in hBM-MSCs, suggesting a role of leptin in mediating the inverse regulation of IL-17A on osteogenesis and adipogenesis in hBM-MSCs. Therefore, the IL-17A-induced leptin production may provide a key clue to understand a molecular mechanism on the lineage commitment of hBM-MSCs into adipocytes or osteoblasts. In addition, leptin production in extra-adipose tissues like MSCs and osteoblasts should be considered in future studies on leptin-associated human diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Evidence that plasma leptin and insulin levels are associated with body adiposity via different mechanisms.

    Science.gov (United States)

    Schwartz, M W; Prigeon, R L; Kahn, S E; Nicolson, M; Moore, J; Morawiecki, A; Boyko, E J; Porte, D

    1997-09-01

    Like insulin, the adipocyte hormone, leptin, circulates at levels proportionate to body adiposity. Because insulin may regulate leptin secretion, we sought to determine if plasma leptin levels are coupled to body adiposity via changes in circulating insulin levels or insulin sensitivity and whether leptin secretion from adipocytes is impaired in subjects with NIDDM. We used multiple linear regression to analyze relationships between BMI (a measure of body adiposity) and fasting plasma levels of leptin and insulin in 98 nondiabetic human subjects (68 men/30 women) and 38 subjects with NIDDM (27 men/11 women). The insulin sensitivity index (Si) was also determined in a subset of nondiabetic subjects (n = 38). Fasting plasma leptin concentrations were correlated to both BMI (r = 0.66, P = 0.0001) and fasting plasma insulin levels (r = 0.65, P = 0.0001) in nondiabetic men and women (r = 0.58, P = 0.0009 for BMI; r = 0.47, P = 0.01 for insulin). While the plasma leptin level was also inversely related to Si (r = -0.35; P = 0.03), this association was dependent on BMI, whereas the association between insulin and Si was not. Conversely, the relationship between plasma leptin and BMI was independent of Si, whereas that between insulin and BMI was dependent on Si. The relationship between plasma leptin levels and BMI did not differ significantly among NIDDM subjects from that observed in nondiabetic subjects. We conclude that 1) body adiposity, sex, and the fasting insulin level are independently associated with plasma leptin level; 2) because NIDDM does not influence leptin levels, obesity associated with NIDDM is unlikely to result from impaired leptin secretion; and 3) insulin sensitivity contributes to the association between body adiposity and plasma levels of insulin, but not leptin. The mechanisms underlying the association between body adiposity and circulating levels of these two hormones, therefore, appear to be different.

  7. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase

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    Stefanou Nikolaos

    2010-08-01

    Full Text Available Abstract Background Numerous epidemiological studies have documented that obesity is associated with hepatocellular carcinoma (HCC. The aim of this study was to investigate the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and human telomerase reverse transcriptase (hTERT, a known mediator of cellular immortalization. Methods We investigated the relationship between leptin, leptin receptors and hTERT mRNA expression in HCC and healthy liver tissue samples. In HepG2 cells, chromatin immunoprecipitation assay was used to study signal transducer and activator of transcription-3 (STAT3 and myc/mad/max transcription factors downstream of leptin which could be responsible for hTERT regulation. Flow cytometry was used for evaluation of cell cycle modifications and MMP1, 9 and 13 expression after treatment of HepG2 cells with leptin. Blocking of leptin's expression was achieved using siRNA against leptin and transfection with liposomes. Results We showed, for the first time, that leptin's expression is highly correlated with hTERT expression levels in HCC liver tissues. We also demonstrated in HepG2 cells that leptin-induced up-regulation of hTERT and TA was mediated through binding of STAT3 and Myc/Max/Mad network proteins on hTERT promoter. We also found that leptin could affect hepatocellular carcinoma progression and invasion through its interaction with cytokines and matrix mettaloproteinases (MMPs in the tumorigenic microenvironment. Furthermore, we showed that histone modification contributes to leptin's gene regulation in HCC. Conclusions We propose that leptin is a key regulator of the malignant properties of hepatocellular carcinoma cells through modulation of hTERT, a critical player of oncogenesis.

  8. Reference values for serum leptin in healthy non-obese children and adolescents.

    Science.gov (United States)

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Louise Hedley, Paula; Esmann Fonvig, Cilius; Stjernholm, Theresa; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian

    2016-11-01

    Adipokines are biologically active, low-molecular weight peptides, which play a major role in metabolic homeostasis in humans. Leptin has gained increasing attention in pediatrics as a biomarker for various metabolic pathologies. Yet, its usefulness is hampered by the relative lack of reference values from pediatric settings. Accordingly, this study aims to evaluate serum concentrations of leptin, soluble leptin receptor (sOB-R), and free leptin index (FLI) in healthy Danish schoolchildren aged 6-18 years and subsequently to establish reference intervals across sex and age groups. A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6-18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free leptin index were calculated using the General Additive Model for Location Scale and Shape (GAMLSS). Significant age and sex-dependent differences in circulating leptin levels were found. In boys, the median leptin concentration for all ages combined was 3.35 μg/L (95%-interval: 0.71-22.47) and in girls, it was 9.89 ng/L (95%-interval: 2.06-41.49). For SOB-R, no sex-specific difference was found, and the median sOB-R concentration was 8.24 μg/L (IQR: 3.58-23.74; range: < 1.56-744.15). We demonstrated an age-dependent correlation with both serum leptin concentration and free leptin index with a gradual and significant increase in girls throughout childhood and adolescence and a significantly higher leptin concentration and free leptin index bell-shaped peak in early adolescence in boys.

  9. Leptin differentially regulates chondrogenesis in mouse vertebral and tibial growth plates.

    Science.gov (United States)

    Yu, Bo; Jiang, Kaibiao; Chen, Bin; Wang, Hantao; Li, Xinfeng; Liu, Zude

    2017-05-31

    Leptin plays an important role in mediating chondrogenesis of limb growth plate. Previous studies suggest that bone structures and development of spine and limb are different. The expression of Ob-Rb, the gene that encodes leptin receptors, is vertebral and appendicular region-specific, suggesting the regulation of leptin on VGP and TGP chondrogenesis may be very different. The aim of the present study was to investigate the differential regulation of leptin on the chondrogenesis of vertebral growth plate (VGP) and tibial growth plate (TGP). We compared the VGP and TGP from wild type (C57BL/6) and leptin-deficient (ob/ob) mice. We then generated primary cultures of TGP and VGP chondrocytes. By treating the primary cells with different concentrations of leptin in vitro, we analyzed proliferation and apoptosis of the primary chondrocytes from TGP and VGP. We further measured expression of chondrogenic-related genes in these cells that had been incubated with different doses of leptin. Leptin-deficient mice of 8-week-old had shorter tibial and longer vertebral lengths than the wide type mice. Disturbed columnar structure was observed for TGP but not for VGP. In primary chondrocyte cultures, leptin inhibited VGP chondrocyte proliferation but promoted their apoptosis. Collagen IIA and aggrecan mRNA, and the protein levels of proliferation- and chondrogenesis-related markers, including PCNA, Sox9, and Smad4, were downregulated by leptin in a dose-dependent manner. In contrast, leptin stimulated the proliferation and chondrogenic differentiation of TGP chondrocytes at physiological levels (i.e., 10 and 50 ng/mL) but not at high levels (i.e., 100 and 1000 ng/mL). Leptin exerts a stimulatory effect on the proliferation and chondrogenic differentiation of the long bone growth plate but an inhibitory effect on the spine growth plate. The ongoing study will shed light on the regulatory mechanisms of leptin in bone development and metabolism.

  10. The molecular mechanism of leptin secretion and expression induced by aristolochic acid in kidney fibroblast.

    Directory of Open Access Journals (Sweden)

    Tsung-Chieh Lin

    Full Text Available BACKGROUND: Leptin is a peptide hormone playing pivotal role in regulating food intake and energy expenditure. Growing evidence has suggested the pro-inflammatory and fibrogenic properties of leptin. In addition, patients with renal fibrosis have higher level of plasma leptin, which was due to the increased leptin production. Aristolochic acid (AA is a botanical toxin characterized to associate with the development of renal fibrosis including tubulointerstitial fibrosis. However, whether leptin is upregulated to participate in AA-induced kidney fibrosis remain completely unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, leptin expression was increased by sublethal dose of AA in kidney fibroblast NRK49f determined by enzyme-linked immunosorbent assay and Western blot. Data from real-time reverse transcriptase-polymerase chain reaction revealed that leptin was upregulated by AA at transcriptional level. DNA binding activity of CCAAT enhancer binding protein α (C/EBP α, one of the transcription factors for leptin gene, was enhanced in DNA affinity precipitation assay and chromatin immunoprecipitation experiments. Knockdown of C/EBP α expression by small interfering RNA markedly reduced AA-induced leptin expression. Moreover, AA promoted Akt interaction with p-PDK1, and increased phosphorylated activation of Akt. Akt knockdown, and inhibition of Akt signaling by LY294002 and mTOR inhibitor rapamycin reduced leptin expression. Furthermore, treatment of LY294002 or rapamycin significantly suppressed AA-induced C/EBP α DNA-binding activity. These results suggest that Akt and C/EBP α activation were involved in AA-regulated leptin expression. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the first that AA could induce secretion and expression of fibrogenic leptin in kidney fibroblasts, which reveal potential involvement of leptin in the progression of kidney fibrosis in aristolochic acid nephropathy.

  11. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase

    International Nuclear Information System (INIS)

    Stefanou, Nikolaos; Papanikolaou, Vassilis; Furukawa, Yoichi; Nakamura, Yusuke; Tsezou, Aspasia

    2010-01-01

    Numerous epidemiological studies have documented that obesity is associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and human telomerase reverse transcriptase (hTERT), a known mediator of cellular immortalization. We investigated the relationship between leptin, leptin receptors and hTERT mRNA expression in HCC and healthy liver tissue samples. In HepG2 cells, chromatin immunoprecipitation assay was used to study signal transducer and activator of transcription-3 (STAT3) and myc/mad/max transcription factors downstream of leptin which could be responsible for hTERT regulation. Flow cytometry was used for evaluation of cell cycle modifications and MMP1, 9 and 13 expression after treatment of HepG2 cells with leptin. Blocking of leptin's expression was achieved using siRNA against leptin and transfection with liposomes. We showed, for the first time, that leptin's expression is highly correlated with hTERT expression levels in HCC liver tissues. We also demonstrated in HepG2 cells that leptin-induced up-regulation of hTERT and TA was mediated through binding of STAT3 and Myc/Max/Mad network proteins on hTERT promoter. We also found that leptin could affect hepatocellular carcinoma progression and invasion through its interaction with cytokines and matrix mettaloproteinases (MMPs) in the tumorigenic microenvironment. Furthermore, we showed that histone modification contributes to leptin's gene regulation in HCC. We propose that leptin is a key regulator of the malignant properties of hepatocellular carcinoma cells through modulation of hTERT, a critical player of oncogenesis

  12. Abalation of Ghrelin receptor in leptin-deficient mice has paradoxical effects on glucose homeostasis compared to Ghrelin-abalated Leptin-deficient mice

    Science.gov (United States)

    Ghrelin is produced predominantly in stomach and is known to be the endogenous ligand of the growth hormone secretagogue receptor (GHSR). Ghrelin is a GH stimulator and an orexigenic hormone. In contrast, leptin is an anorexic hormone, and leptin-deficient ob/ob mice are obese and diabetic. To study...

  13. The role of leptin in human lipid and glucose metabolism: the effects of acute recombinant human leptin infusion in young healthy males

    DEFF Research Database (Denmark)

    Wolsk, Emil; Mygind, Helene; Grøndahl, Thomas S

    2011-01-01

    Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents.......Obese and lean humans treated with leptin have not experienced convincing weight-loss results compared with the dramatic weight losses observed in obese rodents....

  14. Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action.

    Science.gov (United States)

    Calvino, Camila; Souza, Luana L; Costa-e-Sousa, Ricardo H; Almeida, Norma A S; Trevenzoli, Isis H; Pazos-Moura, Carmen C

    2012-10-01

    Leptin has been shown to regulate the hypothalamus-pituitary-thyroid axis, acting primarily through the STAT3 pathway triggered through the binding of leptin to the long-chain isoform of the leptin receptor, ObRb. We previously demonstrated that although hyperthyroid rats presented leptin effects on TSH secretion, those effects were abolished in hypothyroid rats. We addressed the hypothesis that changes in the STAT3 pathway might explain the lack of TSH response to leptin in hypothyroidism by evaluating the protein content of components of leptin signalling via the STAT3 pathway in the hypothalamus and pituitary of hypothyroid (0·03% methimazole in the drinking water/21 days) and hyperthyroid (thyroxine 5 μg/100 g body weight /5 days) rats. Hypothyroid rats exhibited decreased ObRb and phosphorylated STAT3 (pSTAT3) protein in the hypothalamus, and in the pituitary gland they exhibited decreased ObRb, total STAT3, pSTAT3 and SOCS3 (P<0·05). Except for a modest decrease in pituitary STAT3, no other alterations were observed in hyperthyroid rats. Moreover, unlike euthyroid rats, the hypothyroid rats did not exhibit a reduction in food ingestion after a single injection of leptin (0·5 mg/kg body weight). Therefore, hypothyroidism decreased ObRb-STAT3 signalling in the hypothalamus and pituitary gland, which likely contributes to the loss of leptin action on food intake and TSH secretion, as previously observed in hypothyroid rats.

  15. Serum Leptin Levels in Women with Immunological Recurrent Abortion

    Science.gov (United States)

    Zarei, Saeed; Soltanghoraee, Haleh; Mohammadzadeh, Afsaneh; Arefi, Soheila; Zarnani, Amir Hassan; Idali, Farah; Tavangar, Banafsheh; Savadi Shiraz, Elham; Moshref Behzad, Narges; Jeddi-Tehrani, Mahmood

    2010-01-01

    Introduction Recurrent abortion (RA) may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that autoantibodies contribute to reproductive failure. Production of such antibodies is under the control of cytokines; and leptin, besides its role in reproductive success, has a profound effect on directing the cytokine profile toward Th1 (cellular) pattern. Therefore, the present study was performed to assess serum leptin levels in women with immunological recurrent abortion. Materials and Methods In this prospective study, 250 women who attended Avicenna Infertility Clinic with RA were screened for known causes of abortion from July to December 2008 in Tehran, Iran. Eighty-one patients with normal karyotypes and hormonal profile with normal ovaries and uterus and no signs of infection were categorized as patients with immunological (IRA, n = 39) or unexplained (URA, n = 42) recurrent abortion based on presence or absence of autoantibodies. After blood sampling, levels of anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA), lupus anti-coagulant antibody (LACAb), anti-phospholipid antibody (APA), anti-cardiolipin antibody (ACA), anti-thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb) and anti-thrombin III antibody (ATIIIAb) were measured by enzyme-linked immunosorbent assay (ELISA) or chemiluminescent enzyme immunoassay (CLEIA). Results In IRA group, 9 (23.1%), 24 (61.5%), 25(64.1%) and 1 (2.6%) women were above the normal cut-off point for ANA, TgAbs, TPOAbs and AT-III Abs, respectively. IRA patients had normal values of LACAbs, APA and ACA. With normal level of fasting blood sugar (FBS), IRA and URA groups had similar serum leptin levels (23.7 ± 13.2 ng/ml vs. 22.7 ± 12.5 ng/ml, respectively). Serum leptin concentrations showed a positive correlation with weight

  16. The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

    Science.gov (United States)

    Ho, Hoang V T; Sievenpiper, John L; Zurbau, Andreea; Blanco Mejia, Sonia; Jovanovski, Elena; Au-Yeung, Fei; Jenkins, Alexandra L; Vuksan, Vladimir

    2016-10-01

    Oats are a rich source of β-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat β-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat β-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, Pcholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, PLDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat β-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

  17. Leptin as regulator of pulmonary immune responses: involvement in respiratory diseases.

    Science.gov (United States)

    Vernooy, Juanita H J; Ubags, Niki D J; Brusselle, Guy G; Tavernier, Jan; Suratt, Benjamin T; Joos, Guy F; Wouters, Emiel F M; Bracke, Ken R

    2013-08-01

    Leptin is an adipocyte-derived hormone, recognized as a critical mediator of the balance between food intake and energy expenditure by signalling through its functional receptor (Ob-Rb) in the hypothalamus. Structurally, leptin belongs to the long-chain helical cytokine family, and is now known to have pleiotropic functions in both innate and adaptive immunity. The presence of the functional leptin receptor in the lung together with evidence of increased airspace leptin levels arising during pulmonary inflammation, suggests an important role for leptin in lung development, respiratory immune responses and eventually pathogenesis of inflammatory respiratory diseases. The purpose of this article is to review our current understanding of leptin and its functional role on the different resident cell types of the lung in health as well as in the context of three major respiratory conditions being chronic obstructive pulmonary disease (COPD), asthma, and pneumonia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The clinical meanings of leptin RIA in patients with chronic renal failure

    International Nuclear Information System (INIS)

    Zhang Baoqing; Chen Yongsheng; Zhao Yuexia; Wang Yihai

    2006-01-01

    Objective: To explore the relationship between chronic renal failure and serum leptin levels in patients with chronic renal failure. Methods: Serum leptin levels (with RIA) were determined in 134 patients (male, 73, female 61) with chronic renal failure and 40 controls. Results: The serum levels of leptin in the chronic renal failure group were significantly higher than those in the controls (t=2.39, P<0.01). There were no significant differences among the leptin levels in patients with different stages of renal failure. Conclusion: There were hyper-leptinemia and leptin resistance in patients with chronic renal failure. The increase of leptin levels is thought to be harmful in patients with chronic renal failure, however, the precise mechanism remains to be studied further. (authors)

  19. Involvement of leptin in hypophagia induced by the serotonin precursor 5-hydroxytryptophan (5-HTP) in mice.

    Science.gov (United States)

    Yamada, Jun; Sugimoto, Yumi; Ujikawa, Masanori

    2006-03-01

    We previously demonstrated that a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) increases serum leptin levels in mice. It was reported that administration of 5-HTP elicits hypophagia in rodents and humans. In the present study, we examined involvement of leptin in 5-HTP-elicited decreases in the milk intake of fasted mice. Serum leptin levels increased with increases in milk intake in mice, while 5-HTP strongly decreased milk intake in fasted mice compared to that in the control group. Serum leptin levels in fasted mice treated with 5-HTP were similar to those control mice after milk intake. As leptin is a powerful anorectic signal, 5-HTP-induced anorexia may be mediated by facilitation of leptin secretion.

  20. HER2 induces expression of leptin in human breast epithelial cells

    Directory of Open Access Journals (Sweden)

    Aree Moon

    2012-12-01

    Full Text Available A close association between the obesity hormone leptin andbreast cancer progression has been suggested. The presentstudy investigated the molecular mechanism for enhancedleptin expression in breast cancer cells and its functionalsignificance in breast cancer aggressiveness. We examinedwhether leptin expression level is affected by the oncoproteinhuman epidermal growth factor receptor2 (HER2, which isoverexpressed in ∼30% of breast tumors. Here, we report, forthe first time, that HER2 induces transcriptional activation ofleptin in MCF10A human breast epithelial cells. We alsoshowed that p38 mitogen-activated protein kinase signalingwas involved in leptin expression induced by HER2. Weshowed a crucial role of leptin in the invasiveness ofHER2-MCF10A cells using an siRNA molecule targeting leptin.Taken together, the results indicate a molecular link betweenHER2 and leptin, providing supporting evidence that leptinrepresents a target for breast cancer therapy.

  1. Association of leptin with hemodialysis-related muscle cramps: a cross-sectional study.

    Science.gov (United States)

    Hung, Chung-Ying; Chen, Yung-Liang; Chen, Chiou-Shya; Yang, Chwei-Shiun; Peng, Sheng-Jeng

    2009-01-01

    The mechanism of muscle cramp in hemodialysis patients is not well understood. Leptin, a middle molecule uremic toxin, is able to affect neuronal activity. This study aimed to determine the association between leptin and hemodialysis-related muscle cramps. A total of 79 hemodialysis patients were enrolled. The episodes of hemodialysis-related muscle cramps were recorded over a 28-day period. Serum levels of leptin were measured on the 15th day, a mid-week dialysis session. Frequent hemodialysis-related cramps were associated with old age and elevated serum leptin levels. The risk of frequent hemodialysis-related cramps increased with increasing tertiles of leptin concentration. This relationship remained significant after adjustment for age, mean ultrafiltration ratio, gender, body mass index, insulin, resistin, c-reactive protein, albumin, peripheral arterial disease, electrolytes, and beta(2)-microglobulin. Leptin levels are associated with frequent hemodialysis-related cramps. Further studies are necessary to elucidate the underlying mechanisms.

  2. Leptin and insulin signaling in dopaminergic neurons: relationship between energy balance and reward system.

    Science.gov (United States)

    Khanh, Doan V; Choi, Yun-Hee; Moh, Sang Hyun; Kinyua, Ann W; Kim, Ki Woo

    2014-01-01

    The central actions of leptin and insulin are essential for the regulation of energy and glucose homeostasis. In addition to the crucial effects on the hypothalamus, emerging evidence suggests that the leptin and insulin signaling can act on other brain regions to mediate the reward value of nutrients. Recent studies have indicated the midbrain dopaminergic neurons as a potential site for leptin' and insulin's actions on mediating the feeding behaviors and therefore affecting the energy balance. Although molecular details about the integrative roles of leptin and insulin in this subset of neurons remain to be investigated, substantial body of evidence by far imply that the signaling pathways regulated by leptin and insulin may play an essential role in the regulation of energy balance through the control of food-associated reward. This review therefore describes the convergence of energy regulation and reward system, particularly focusing on leptin and insulin signaling in the midbrain dopaminergic neurons.

  3. Changes of serum leptin and c-peptide level in children with type 1 diabetic mellitus

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng; Sun Junjiang; Wang Shukui; Qi Shaokang

    2001-01-01

    To deplore the relationship between leptin and c-peptide in children with type 1 diabetic mellitus (DM). The levels of serum leptin and c-peptide (C-P) in 65 type 1 DM children (including 31 before and after insulin treatment) and 30 normal controls were measured by radioimmunoassay (RIA). The results found that there was significant differences (P < 0.01) in leptin and C-P between DM children and normal controls, also in 31 DM children before and after treatment. It showed a positive correlation between leptin and C-P. The changes of the leptin/C-P ratio in DM children compared with normal controls and that before and after treatment were also significantly different. It suggested that leptin may have close relationship in the development, progress and the occurrence of complications in children with DM and also provide a new clue for their diagnosis treatment and complication occurrence

  4. Clinical value of combined determining leptin, T and E2 in male teenager obesity patients

    International Nuclear Information System (INIS)

    Bai Zhenlian; Lv Tongqin; Wu Qiuhua

    2006-01-01

    To study clinical significance of combined detection of leptin, T and E 2 for teenager obesity patients, levels of leptin, T and E 2 in male teenagers obesity patients and male adult obesity patients were determined by RIA. The result showed that in all obesity patients, the levels of leptin and E 2 were much higher than those in normal controls and T was lower than that in normal controls. After treatment, leptin and E 2 were decreased and T was increased significantly in teenager obesity patients, but only leptin was decreased in adult obesity patients. All results indicate that combined detection of leptin, T and E 2 could find endocrine and metabolism disorder of obese teenagers at early stage, instituting prevention and treatment without delay.(authors)

  5. Leptine: an hormone secreted by adipose tissue. First study in Uruguayan population sample

    International Nuclear Information System (INIS)

    Pisabarro, Raul; Irrazabal, Ernesto; Recalde, Alicia; Barrios, Enrique; Arocena, Beatriz; Garcia Loriente, Jose Maria; Lorenzo Bonifazio, Juan

    1999-01-01

    The recent discovery of leptine, an hormone secreted by adipose tissue which modulates the energetic expenditure has signified a gigantic advance in studying obesity facts. In spite of a recent description of absence of leptine in humans, the obesity human model answers to leptine resistance. In this paper, we revise the actual concepts and show leptine values of a sample of 101 middle aged uruguayans, male and female, of normal weight and over weighted (table 1), correlated with corporal mass index (CMI) as an indirect measure of total body fat and waist diameter as an indirect measure of visceral fat, and hips (periferical fat). Bioimpedance studies were carried out to get the corporal composition. Results: good correlation between corporal fat and leptine, but fat distribution was not found representative. All in all, this data set confirms the correlation between leptine and total body fat mass

  6. Association of serum leptin with serum C-reactive protein in hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Rastegari Ebrahim

    2012-04-01

    Full Text Available Introduction: Recent investigations have shown that leptin is cleared principally by the kidney. Objectives: To examine whether and how in patients on hemodialysis the level of C-reactive protein level correlate with serum leptin. Patients and Methods: The total patients were 36. The mean patients’ age were 46 (16 years. The median length of the time patients were on hemodialysis were 19 months. Results: The mean serum C-reactive protein was 8.7 (6.6 mg/l (median: 8 mg/l. The mean serum leptin was 9.4 (14 ng/ml (median: 5.75 ng/ml. In this study we found a significant inverse correlation of serum leptin with serum C-reactive protein (r= -0.57, p= 0.041 was seen. Conclusion: Our data supports, the positive effect of leptin on nutrition and support the theory of protective effects (reverse epidemiology of leptin in hemodialysis patients.

  7. Serum leptin level and its significance in chronic renal failure hemodialysis patients

    International Nuclear Information System (INIS)

    Zhang Yong; You Yuping; Chen Weizhen; Mo Congjian

    2003-01-01

    To study serum leptin level in chronic renal failure (CRF) hemodialysis patients and the relationship between serum leptin level and residue renal function, body composition, and indices of malnutrition, 31 end-stage CRF hemodialysis patients and 38 healthy people were enrolled. Serum leptin levels were detected by radioimmunoassay. BMI, %Fat and LBM were measured by bioelectrical impedance analysis device. Alb, Chol, Hgb, BUN, SCr and Ccr of the patients were also examined. Results showed that Serum leptin level in end-stage CRF hemodialysis patients was markedly higher than that in healthy controls (P 0.05). Conclusion: Hyperleptinemia existed in end-stage CRF hemodialysis patients and might cause the loss of LBM. The leptin level was not correlated with residue renal function, but it could reflect the fat content. However, serum leptin did not play a significant role in protein malnutrition in end-stage CRF hemodialysis patients

  8. The plasma leptin concentration is closely associated with the body fat mass in nondiabetic uremic patients

    DEFF Research Database (Denmark)

    Clausen, P; Nielsen, P K; Olgaard, K

    1999-01-01

    Plasma leptin is associated with the body mass index and, more precisely, with the body fat mass. Plasma leptin has been found to be elevated in uremic patients. This study aimed at investigating the plasma leptin concentration and associations between plasma leptin, body fat mass, and glomerular...... filtration rate in nondiabetic predialysis uremic patients and in nondiabetic patients on chronic hemodialysis. Plasma leptin, body fat mass, and creatinine clearance were measured in 22 predialysis uremic patients, 18 hemodialysis patients, and 24 healthy control subjects. The logarithmically transformed...... plasma leptin concentration was closely associated with the body fat mass in all groups (r = 0.93, r = 0.83, and r = 0.72, respectively; p

  9. Study on the relationship between serum levels of leptin thyroid hormones

    International Nuclear Information System (INIS)

    Lin Pingan; Zhai Chuntao; Yuan Sufen

    2005-01-01

    Objective: To evaluate the relationship between serum levels of leptin and thyroid functional status. Methods: Serum leptin (with RIA) and pituitary-thyroid axis hormones (with CLIA) were measured in 75 euthyroid controls, 44 hyperthyroid subjects and 27 hypothyroid subjects. Results: The levels of leptin in euthyroid controls, hyperthyroid subjects and hypothyroid subjects were (5.40 ± 3.78) ng/ml, (5.99 ± 5.24) ng/ml and (5.59 ± 4.23) ng/ml respectively with no significant differences among them. The serum leptin levels were positively correlated with serum TSH levels (r=0.27, P<0.01). Conclusion: Thyroid function has no effect on serum leptin levels and TSH levels correlates closely with those of serum leptin. (authors)

  10. Common Genetic Components of Obesity Traits and Serum Leptin

    DEFF Research Database (Denmark)

    Hasselbalch, Ann L; Benyamin, Beben; Visscher, Peter M

    2008-01-01

    To estimate common and distinct genetic influences on a panel of obesity-related traits and serum leptin level in adults. In a cross-sectional study of 625 Danish, adult, healthy, monozygotic, and same-sex dizygotic twin pairs of both genders, we carried out detailed anthropometry (height, weight...... components, which suggests that it is important to distinguish between the different phenotypes in the search for genes involved in the development of obesity.Obesity (2008) doi:10.1038/oby.2008.440........ For leptin vs. the various measures of overall and local fatness the correlations ranged from 0.54 to 0.74 in men and from 0.48 to 0.75 in women. All correlations were significantly different genetic...

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

    Science.gov (United States)

    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

  12. Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1 adipocytes deprived of glucose

    Directory of Open Access Journals (Sweden)

    Tomomi Tsubai

    2016-11-01

    Conclusion: Insulin alone stimulates leptin secretion and elevates leptin mRNA levels via cAMP under the lack of glucose metabolism, while glucose is a significant and ambivalent effector on the insulin effects of leptin.

  13. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study.

    Science.gov (United States)

    Zimmet, P; Hodge, A; Nicolson, M; Staten, M; de Courten, M; Moore, J; Morawiecki, A; Lubina, J; Collier, G; Alberti, G; Dowse, G

    1996-10-19

    To measure serum leptin concentrations in the Polynesian population of Western Samoa and to examine epidemiological associations of leptin with anthropometric, demographic, behavioural, and metabolic factors in this population with a high prevalence of obesity and non-insulin dependent diabetes mellitus. Cross sectional study, leptin concentration being measured in a subgroup of a population based sample. 240 Polynesian men and women aged 28-74 years were selected to cover the full range of age, body mass index, and glucose tolerance. Serum leptin, insulin, and glucose concentrations; anthropometric measures; physical activity; and area of residence. Leptin concentrations were correlated with body mass index (r = 0.80 in men, 0.79 in women) and waist circumference (r = 0.82 in men, 0.78 in women) but less so with waist to hip ratio. At any body mass index, leptin concentration was higher in women than men (geometric mean adjusted for body mass index 15.3 v 3.6 pg/l, P < 0.001). Leptin concentration also correlated with fasting insulin concentration (r = 0.63 in men, 0.64 in women) and insulin concentration 2 hours after a glucose load (r = 0.58 in men, 0.52 in women). These associations remained significant after controlling for body mass index; effects of physical activity and of rural or urban living on leptin concentration were eliminated after adjusting for obesity, except values remained high in urban men. 78% of variance in leptin was explained by a model including fasting insulin concentration, sex, body mass index, and a body mass index by sex interaction term. Similar results were obtained if waist circumference replaced body mass index. The strong relation of leptin with obesity is consistent with leptin production being proportional of mass to adipose tissue. The relation with insulin independent of body mass index suggests a possible role for leptin in insulin resistance or hyperinsulinaemia.

  14. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study.

    OpenAIRE

    Zimmet, P.; Hodge, A.; Nicolson, M.; Staten, M.; de Courten, M.; Moore, J.; Morawiecki, A.; Lubina, J.; Collier, G.; Alberti, G.; Dowse, G.

    1996-01-01

    OBJECTIVE: To measure serum leptin concentrations in the Polynesian population of Western Samoa and to examine epidemiological associations of leptin with anthropometric, demographic, behavioural, and metabolic factors in this population with a high prevalence of obesity and non-insulin dependent diabetes mellitus. DESIGN: Cross sectional study, leptin concentration being measured in a subgroup of a population based sample. SUBJECTS: 240 Polynesian men and women aged 28-74 years were selected...

  15. Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice

    Science.gov (United States)

    Winters, B.; Mo, Z.; Brooks-Asplund, E.; Kim, S.; Shoukas, A.; Li, D.; Nyhan, D.; Berkowitz, D. E.

    2000-01-01

    Obesity is a major health care problem and is associated with significant cardiovascular morbidity. Leptin, a neuroendocrine hormone released by adipose tissue, is important in modulating obesity by signaling satiety and increasing metabolism. Moreover, leptin receptors are expressed on vascular endothelial cells (ECs) and mediate angiogenesis. We hypothesized that leptin may also play an important role in vasoregulation. We investigated vasoregulatory mechanisms in the leptin-deficient obese (ob/ob) mouse model and determined the influence of leptin replacement on endothelial-dependent vasorelaxant responses. The direct effect of leptin on EC nitric oxide (NO) production was also tested by using 4, 5-diaminofluorescein-2 diacetate staining and measurement of nitrate and nitrite concentrations. Vasoconstrictor responses to phenylephrine, norepinephrine, and U-46619 were markedly enhanced in aortic rings from ob/ob mice and were modulated by NO synthase inhibition. Vasorelaxant responses to ACh were markedly attenuated in mesenteric microvessels from ob/ob mice. Leptin replacement resulted in significant weight loss and reversal of the impaired endothelial-dependent vasorelaxant responses observed in ob/ob mice. Preincubation of ECs with leptin enhanced the release of NO production. Thus leptin-deficient ob/ob mice demonstrate marked abnormalities in vasoregulation, including impaired endothelial-dependent vasodilation, which is reversed by leptin replacement. These findings may be partially explained by the direct effect of leptin on endothelial NO production. These vascular abnormalities are similar to those observed in obese, diabetic, leptin-resistant humans. The ob/ob mouse may, therefore, be an excellent new model for the study of the cardiovascular effects of obesity.

  16. Comparitive Study of Serum Leptin Levels in Diabetic Obese Patients and Non-Diabetic Obese Individuals

    OpenAIRE

    M Afkhami-Ardakani; J Mohiti-Ardakani; H Sedghi

    2004-01-01

    Introduction: Leptin was first discovered from the "Ob Gene" by Friedwan and co-workers in 1994. It is a small peptide with 167 amino acids and molecular weight of 16 Kd . It is secreted by adipose tissues. Leptin has two type of receptors in Hypothalamus and other tissues including muscles, liver and intestines. Leptin inhibits neuropeptide Y resulting in decreased appetite and on the other hand increases the basic metabolic rate of the body resulting in homeostasis of body energy. Insulin v...

  17. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kang Nyeong [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Choi, Ho Soon, E-mail: hschoi96@hanyang.ac.kr [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Yang, Sun Young [Department of Internal Medicine, Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul (Korea, Republic of); Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo [Department of Internal Medicine, Hanyang University College of Medicine, Seoul (Korea, Republic of); Paik, Seung Sam [Pathology, Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2014-04-18

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.

  18. The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

    International Nuclear Information System (INIS)

    Lee, Kang Nyeong; Choi, Ho Soon; Yang, Sun Young; Park, Hyun Ki; Lee, Young Yiul; Lee, Oh Young; Yoon, Byung Chul; Hahm, Joon Soo; Paik, Seung Sam

    2014-01-01

    Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways

  19. Astrocytes Modulate Distribution and Neuronal Signaling of Leptin in the Hypothalamus of Obese Avy Mice

    OpenAIRE

    Pan, Weihong; Hsuchou, Hung; Xu, Changlei; Wu, Xiaojun; Bouret, Sebastien G.; Kastin, Abba J.

    2010-01-01

    We tested the hypothesis that astrocytic activity modulates neuronal uptake and signaling of leptin in the adult-onset obese agouti viable yellow (Avy) mouse. In the immunohistochemical study, Avy mice were pretreated with the astrocyte metabolic inhibitor fluorocitrate or phosphate-buffered saline (PBS) vehicle intracerebroventricularly (icv) followed 1 h later by Alexa568-leptin. Confocal microscopy showed that fluorocitrate pretreatment reduced astrocytic uptake of Alexa568-leptin 30 min a...

  20. Polymorphisms in the leptin gene promoter in Brazilian beef herds.

    Science.gov (United States)

    Guimarães, R C; Azevedo, J S N; Corrêa, S C; Campelo, J E G; Barbosa, E M; Gonçalves, E C; Silva Filho, E

    2016-12-02

    Brazil is the world's largest producer of beef cattle; however, the quality of its herds needs to be improved. The use of molecular markers as auxiliary tools in selecting animals for reproduction with high pattern for beef production would significantly improve the quality of the final beef product in Brazil. The leptin gene has been demonstrated to be an excellent candidate gene for bovine breeding. The objective of this study was to sequence and compare the leptin gene promoter of Brazil's important cattle breeds in order to identify polymorphisms in it. Blood samples of the Nellore, Guzerat, Tabapuã, and Senepol breeds were collected for genomic DNA extraction. The genomic DNA was used as a template for polymerase chain reaction (PCR) to amplify a 1575-bp fragment, which in turn was sequenced, aligned, and compared between animals of different breeds. Twenty-three single nucleotide polymorphic sites, including transitions and transversions, were detected at positions -1457, -1452, -1446, -1397, -1392, -1361, -1238, -963,-901, -578, -516, -483, -478, -470, -432, -430, -292, -282, -272, -211, -202, -170, and -147. Additionally, two insertion sites at positions -680 and -416 and two deletion sites at positions -1255 and -1059 were detected. As the promoter region of the leptin gene has been demonstrated to vary among breeds, these variations must be tested for their use as potential molecular markers for artificial selection of animals for enhanced beef production in different systems of bovine production in Brazil.

  1. Effect of Technological Treatments on Human-Like Leptin Level in Bovine Milk for Human Consumption.

    Science.gov (United States)

    Magistrelli, Damiano; Rosi, Fabia

    2014-07-23

    In this experiment, raw milk and commercially available full-cream UHT milk, semi-skimmed UHT milk, skimmed UHT milk, full-cream pasteurized milk, semi-skimmed pasteurized milk and infant formulas for babies between 6 and 12 months of age were analyzed by RIA, with a method using an antibody directed against human leptin and human leptin as reference standard. Raw milk and full-cream UHT milk did not differ for human-like leptin. Leptin content of full-cream pasteurized milk was not different to that of full-cream UHT milk, but it was 14% lower ( p raw milk. Human-like leptin level of semi-skimmed UHT milk was not different to that of semi-skimmed pasteurized milk, but it was 30% lower ( p pasteurized milks. In skimmed UHT milk, leptin was 40% lower ( p milk. Leptin was correlated ( p milks. Results suggest that the heat treatment (pasteurization or UHT) is not a modifier of human-like leptin content of edible commercial bovine milks, whereas the skimming process significantly reduces milk leptin level.

  2. Increased leptin levels in preeclampsia: associations with BMI, estrogen and SHBG levels.

    Science.gov (United States)

    Acromite, Michael; Ziotopoulou, Mary; Orlova, Christine; Mantzoros, Christos

    2004-01-01

    Leptin is secreted mainly by the white adipose tissue but is also synthesized in several non-adipose tissue organs including the placenta. Serum leptin levels are increased in normal pregnancies and are higher in preeclamptic than normal pregnant women. There is, however, a lack of empirical evidence of an independent association of serum leptin levels and preeclamsia. We have studied cross-sectionally 18 3rd trimester preeclamptic women, 28 3rd trimester and 30 2nd trimester control women to confirm the reported increase of serum leptin in preeclampsia and to assess whether elevated leptin levels in preeclampsia increase the variance explained by body mass index (BMI), androgens, estrogens and/or sex hormone binding globulin (SHBG). Anthropometric, demographic and hormonal data were analyzed using linear and logistic regression models. Leptin is significantly increased in preeclampsia by univariate analysis, but use of multivariate analysis indicates that the elevated leptin levels are not associated with preeclampsia independently from BMI, estrogens and SHBG. This study confirms that leptin levels are higher in women with preeclampsia than in controls and demonstrates that serum leptin levels do not add to the prediction of preeclampsia after accounting for BMI, estrogen and SHBG levels of preeclamptic women.

  3. Subcloning, expression, purification, and characterization of recombinant human leptin-binding domain.

    Science.gov (United States)

    Sandowski, Yael; Raver, Nina; Gussakovsky, Eugene E; Shochat, Suzan; Dym, Orly; Livnah, Oded; Rubinstein, Menachem; Krishna, Radha; Gertler, Arieh

    2002-11-29

    A subdomain of the human leptin receptor encoding part of the extracellular domain (amino acids 428 to 635) was subcloned, expressed in a prokaryotic host, and purified to homogeneity, as evidenced by SDS-PAGE, with over 95% monomeric protein. The purified leptin-binding domain (LBD) exhibited the predicted beta structure, was capable of binding human, ovine, and chicken leptins, and formed a stable 1:1 complex with all mammalian leptins. The binding kinetics, assayed by surface plasmon resonance methodology, showed respective k(on) and k(off) values (mean +/- S.E.) of 1.20 +/- 0.23 x 10(-5) mol(-1) s(-1) and 1.85 +/- 0.30 x 10(-3) s(-1) and a K(d) value of 1.54 x 10(-8) m. Similar results were achieved with conventional binding experiments. LBD blocked leptin-induced, but not interleukin-3-induced, proliferation of BAF/3 cells stably transfected with the long form of human leptin receptor. The modeled LBD structure and the known three-dimensional structure of human leptin were used to construct a model of 1:1 LBD.human leptin complex. Two main residues, Phe-500, located in loop L3, and Tyr-441, located in L1, are suggested to contribute to leptin binding.

  4. Leptin concentrations do not predict weight gain: the Mexico City Diabetes Study.

    Science.gov (United States)

    Haffner, S M; Mykkänen, L A; Gonzalez, C C; Stern, M P

    1998-07-01

    Leptin, a hormone which is produced by adipose tissue, has been shown to inhibit food intake and increase energy expenditure. In humans, leptin levels are correlated with body fat. In addition, leptin levels decline in subjects who lose weight. Yet few data exist on whether leptin levels predict weight change, except for a recent report suggesting that low leptin levels predict weight gain in very obese middle-aged Pima Indians. We have examined the association between baseline leptin levels and subsequent weight gain over 3.25 y in 180 non-diabetic participants in the Mexico City Diabetes Study. At baseline, the correlation between leptin levels and body mass index (BMI) was 0.712 in men and 0.691 in women (both P BMI (+/- 2 kg/m2) at baseline. Baseline BMI was 25.3 kg/m2 in men and 27.2 kg/m2 in women. Baseline leptin levels (ng/ml) did not predict weight gain in either men (weight gainers: 4.3; weight stable: 5.8; and weight losers: 5.2) or women (weight gainers: 17.4; weight stable: 17.7; and weight losers: 17.4). We conclude that baseline leptin levels did not predict weight change in moderately obese individuals.

  5. Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

    International Nuclear Information System (INIS)

    Nour Eldin, A.M.

    2004-01-01

    The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

  6. Effect of vanadium on insulin and leptin in Zucker diabetic fatty rats.

    Science.gov (United States)

    Wang, J; Yuen, V G; McNeill, J H

    2001-02-01

    Vanadium exhibits a variety of insulin-mimetic actions in vitro and in vivo. The mechanism(s) of the effect of vanadium on leptin in Zucker diabetic fatty (ZDF) rats, a model of Type 2 diabetes, is unclear. Since insulin is a stimulator of leptin production and secretion and vanadium is an insulin-mimetic or insulin-enhancing agent, we studied how vanadium affected plasma leptin levels in vivo and the relationship between plasma insulin, leptin and body fat in ZDF rats. Zucker lean and ZDF rats at 9-week old were chronically treated with bis(ethylmaltolato)oxovanadium(IV) (BEOV), an organic vanadium compound, by oral gavage daily for 3 weeks. At termination, the total body fat was weighed and blood was collected for insulin, leptin and glucose assay. BEOV treatment (0.1 mmol/kg/day) significantly decreased plasma glucose levels in ZDF rats and did not change food intake and body fat content either in lean or ZDF rats. Following 3-week treatment, plasma insulin and leptin levels in BEOV treated ZDF rats were significantly higher, 1.5 and 0.5 fold than untreated rats, respectively. The correlation coefficients in ZDF rats showed that plasma leptin levels were correlated to plasma insulin levels, but not to body fat. These data indicate that plasma leptin levels parallel plasma insulin levels, and the effects of vanadium on leptin appear to be mediated by insulin in ZDF rats.

  7. Expression of leptin and iNOS in oral melanomas in dogs.

    Science.gov (United States)

    Greene, V R; Wilson, H; Pfent, C; Roethele, J; Carwile, J; Qin, Y; Grimm, E; Ellerhorst, J A

    2013-01-01

    Oral melanoma (OM) in dogs is an aggressive malignancy, with clinical behavior resembling cutaneous melanomas in humans. Melanoma in humans is promoted by an inflammatory environment that is contributed to by leptin and inducible nitric oxide synthase (iNOS). To determine if the patterns of leptin and iNOS expression are similar in OM in dogs and cutaneous melanomas in humans. Twenty client-owned dogs. Retrospective case study. Immunostaining of the OM tumors from each dog was scored for percentage and intensity of leptin and iNOS expression. Mitotic index was used as an indicator of tumor aggression. Leptin was detected in ≥75% of the tumor cells in specimens from 11 dogs. One tumor expressed leptin in ≤25% of the cells. The intensity of leptin expression was variable with 6, 9, and 5 cases exhibiting low-, moderate-, and high-intensity staining, respectively. OM with the lowest percentage of iNOS positive cells displayed the highest mitotic indices (P = .006, ANOVA). The expression of leptin is a common finding in melanomas in dogs. These data suggest that the possibility of future clinical applications, such as measuring the concentrations of plasma leptin as a screening tool or leptin as a target for therapy. The relevance of iNOS is not as clear in dogs with OM, for which other directed therapeutics might be more appropriate. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  8. Leptin levels distribution and ethnic background in two populations from Chile: Caucasian and Mapuche groups.

    Science.gov (United States)

    Pérez-Bravo, F; Albala, C; Santos, J L; Yañez, M; Carrasco, E

    1998-10-01

    Leptin, the product of the human ob gene is increased in obese individuals, suggesting resistance to its effect. We examined the relationship of serum leptin levels with respect to obesity, gender and insulin levels in two populations with different ethnic compositions in Chile. Leptin and insulin levels were determined by radioimmunoassay (RIA) and correlated with body mass index (BMI), gender and ethnic background. 79 Caucasian subjects from Santiago and 65 Mapuche natives from the Araucania region, Chile, were included in this study. Leptin concentrations in obese subjects were significantly increased in both ethnic groups in relation to lean status: Caucasian and Mapuche obese 19.3 +/- 11.6 and 10.1 +/- 5.8 (P Mapuche lean 10.4 +/- 5.8 and 4.7 +/- 2.9 (P Mapuche and Caucasian groups, similar leptin levels were observed among the males of the two populations in both metabolic states (lean and obese). In contrast, the leptin level distributions between women showed a marked difference, having a minor value in the Mapuche women with a comparable value with the male group in this ethnic population. The leptin concentrations are associated with obesity in both ethnic groups in Chile. However, the leptin levels between the Mapuche natives were significantly decreased compared to the Caucasian group. The gender distribution does not seem to be important in the Mapuche natives. The ethnic composition seems to be important in the leptin distribution in the analysed populations.

  9. GLP-1/glucagon coagonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Chabenne, Joseph; Finan, Brian

    2014-01-01

    We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD......) exposure. Here we assess whether a single peptide possessing balanced coagonism at the glucagon-like peptide 1 (GLP-1) and glucagon receptors can restore leptin responsiveness in DIO mice maintained on a HFD. DIO mice were treated with PEG-GLP-1/glucagon (30 nmol/kg every fourth day) to induce an ∼15% body...

  10. [Relationship between leptin and body mass and metabolic syndrome in an adult population].

    Science.gov (United States)

    Martins, Maria do Carmo; Lima Faleiro, Luís; Fonseca, Aidil

    2012-11-01

    To analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. The study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. BMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (pcorrelations between leptin and IR, and leptin and insulinemia, were strong in both sexes. With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). Elevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  11. The relationship of human milk leptin and macronutrients with gastric emptying in term breastfed infants.

    Science.gov (United States)

    Cannon, Anna M; Gridneva, Zoya; Hepworth, Anna R; Lai, Ching T; Tie, Wan J; Khan, Sadaf; Hartmann, Peter E; Geddes, Donna T

    2017-07-01

    BackgroundInfants breastfed on demand exhibit a variety of feeding patterns and self-regulate their nutrient intake, but factors influencing their gastric emptying (GE) are poorly understood. Despite research into appetite regulation properties of leptin, there is limited information about relationships between human milk leptin and infant GE.MethodsGastric volumes were calculated from ultrasound scans of infants' stomachs (n=20) taken before and after breastfeeding, and then every 12.5 min (median; range: 3-45 min) until the next feed. Skim milk leptin and macronutrient concentrations were measured and doses were calculated.ResultsThe leptin concentration was (mean±SD) 0.51±0.16 ng/ml; the leptin dose was 45.5±20.5 ng per feed. No relationships between both concentration and dose of leptin and time between the feeds (P=0.57; P=1, respectively) or residual stomach volumes before the subsequent feed (P=0.20; P=0.050) were found. Post-feed stomach volumes (GE rate) were not associated with leptin concentration (P=0.77) or dose (P=0.85).ConclusionGE in term breastfed infants was not associated with either skim milk leptin concentration or dose. Further investigation with inclusion of whole-milk leptin and other hormones that affect gastrointestinal activity is warranted.

  12. Leptin affects prolactin action on milk protein and fat synthesis in the bovine mammary gland.

    Science.gov (United States)

    Feuermann, Y; Mabjeesh, S J; Shamay, A

    2004-09-01

    Leptin, a protein hormone produced and secreted predominantly by white adipose tissue, has a critical role in the regulation and coordination of energy metabolism. Identification of leptin in the milk of several mammals, including humans, led us to investigate its presence and regulatory effect in the cow mammary gland. The expression of leptin receptor in tissue culture of lactating mammary gland was augmented approximately 25 times by prolactin, but had no effect on virgin calf mammary tissue. Expression of leptin in tissue culture from mammary glands of lactating cows was enhanced 2.2-fold by prolactin. No effect of prolactin on leptin and leptin receptor expression was found in mammary gland tissue culture from calves. Leptin-enhanced fatty acid synthesis in the presence of prolactin, but had no effect without presence of prolactin. A similar pattern was found in the expression of alpha-casein and beta-lactoglobulin in mammary gland explants from a lactating cow. Our findings indicate that leptin plays an important role in mammary gland lactogenesis, and that the expression of leptin requires the presence of prolactin.

  13. Astrocytes modulate distribution and neuronal signaling of leptin in the hypothalamus of obese A vy mice.

    Science.gov (United States)

    Pan, Weihong; Hsuchou, Hung; Xu, Changlei; Wu, Xiaojun; Bouret, Sebastien G; Kastin, Abba J

    2011-03-01

    We tested the hypothesis that astrocytic activity modulates neuronal uptake and signaling of leptin in the adult-onset obese agouti viable yellow (A vy) mouse. In the immunohistochemical study, A vy mice were pretreated with the astrocyte metabolic inhibitor fluorocitrate or phosphate-buffered saline (PBS) vehicle intracerebroventricularly (icv) followed 1 h later by Alexa568-leptin. Confocal microscopy showed that fluorocitrate pretreatment reduced astrocytic uptake of Alexa568-leptin 30 min after icv while increasing neuronal uptake in the arcuate nucleus and dorsomedial hypothalamus. Fluorocitrate also induced mild astrogliosis and moderately increased pSTAT3 immunopositive neurons in response to Alexa568-leptin in the dorsomedial hypothalamus. In the Western blotting study, A vy mice were pretreated with either PBS or fluorocitrate, and received PBS or leptin 1 h later followed by determination of pSTAT3 and GFAP expression an additional 30 min afterward. The results show that fluorocitrate induced a mild pSTAT3 activation but attenuated leptin-induced pSTAT3 activation and decreased GFAP expression independently of leptin treatment. We conclude that inhibition of astrocytic activity resulted in enhanced neuronal leptin uptake and signaling. This suggests opposite roles of astrocytes and neurons in leptin's actions in the A vy mouse with adult-onset obesity.

  14. Leptin Antagonizes Peroxisome Proliferator-Activated Receptor-γ Signaling in Growth Plate Chondrocytes

    Directory of Open Access Journals (Sweden)

    Lai Wang

    2012-01-01

    Full Text Available Leptin is an obesity-associated cytokine-like hormone encoded by the ob gene. Recent studies reveal that leptin promotes proliferation and differentiation of chondrocytes, suggesting a peripheral role of leptin in regulating growth plate function. Peroxisome proliferator-activated receptor-γ (PPARγ is a transcriptional regulator of adipogenesis. Locally, PPARγ negatively regulates chondrogenic differentiation and terminal differentiation in the growth plate. The aim of this study was to test the hypothesis that leptin may suppress the inhibitory effects of PPARγ on growth plate chondrocytes. Chondrocytes were collected from distal femoral growth plates of newborn rats and were cultured in monolayer or cell pellets in the presence or absence of leptin and the PPARγ agonist ciglitazone. The results show that leptin attenuates the suppressive effects of PPARγ on chondrogenic differentiation and T3-mediated chondrocyte hypertrophy. Leptin treatment also leads to a mild downregulation of PPAR mRNA expression and a significant MAPK/ERK-dependent PPARγ phosphorylation at serine 112/82. Blocking MAPK/ERK function with PD98059 confirmed that leptin antagonizes PPARγ function in growth plate chondrocytes through the MAPK/ERK signaling pathway. Furthermore, leptin signaling in growth plate cells is also negatively modulated by activation of PPARγ, implying that these two signaling pathways are mutually regulated in growth plate chondrocytes.

  15. [Role of leptin and leptin resistance in non-alcoholic fatty liver disease development in persons with obesity and overweight].

    Science.gov (United States)

    Livzan, M A; Lapteva, I V; Miller, T S

    2014-01-01

    To study the impact of leptin and leptinresistance on formation of non-alcoholic fatty liver disease (NAFLD) of people with obesity and overweight. 105 patients with obesity and overweight were examined, among them 19 men and 86 women, median age 58 (50-63) years. Risk factors development NAFLD, anthropometric indices, biochemical analysis of blood, abdominal ultrasonic studies, levels leptin and its soluble receptor were estimated. examined people with NAFLD were included into 2 groups: main group (patients NAFLD, n = 77) and comparison group (n = 28). Waist volume, body mass index, blood glucose were higher in group of patients with NAFLD (p liver development (rs = (0.376), p obesity and overweight negative correlation of moderate strength (rs = (-0.370), p obesity and excess body weight, phenomenon of leptinresistance arises to patients with obesity and can be considered as predictor of the development and progression of NAFLD among this category of patients.

  16. Early childhood BMI trajectories in monogenic obesity due to leptin, leptin receptor, and melanocortin 4 receptor deficiency.

    Science.gov (United States)

    Kohlsdorf, Katja; Nunziata, Adriana; Funcke, Jan-Bernd; Brandt, Stephanie; von Schnurbein, Julia; Vollbach, Heike; Lennerz, Belinda; Fritsch, Maria; Greber-Platzer, Susanne; Fröhlich-Reiterer, Elke; Luedeke, Manuel; Borck, Guntram; Debatin, Klaus-Michael; Fischer-Posovszky, Pamela; Wabitsch, Martin

    2018-02-27

    To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes. Early childhood (0-5 years) BMI trajectories were compared between the groups at selected time points. The LEP and LEPR group showed a tremendous increase in BMI during the first 2 years of life with all patients displaying a BMI >27 kg/m 2 (27.2-38.4 kg/m 2 ) and %BMI P95 (percentage of the 95th percentile BMI for age and sex) >140% (144.8-198.6%) at the age of 2 years and a BMI > 33 kg/m 2 (33.3-45.9 kg/m 2 ) and %BMI P95  > 184% (184.1-212.6%) at the age of 5 years. The MC4R and CTRL groups had a later onset of obesity with significantly lower BMI values at both time points (p BMI trajectories in this pediatric cohort with monogenic obesity we suggest that BMI values >27.0 kg/m 2 or %BMI P95  > 140% at the age of 2 years and BMI values >33.0 kg/m 2 or %BMI P95  > 184% at the age of 5 years may be useful cut points to identify children who should undergo genetic screening for monogenic obesity due to functionally relevant mutations in the leptin gene or leptin receptor gene.

  17. Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERα pathway

    Energy Technology Data Exchange (ETDEWEB)

    Khanal, Tilak; Kim, Hyung Gyun; Do, Minh Truong; Choi, Jae Ho; Won, Seong Su [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Kang, Wonku [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-05-15

    Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells. - Highlights: • Leptin increased 4-hydroxyoestradiol in MCF-7 breast cancer cells. • Leptin activated ERK and Akt kinases related to ERα phosphorylation. • Leptin induces phosphorylation of ERα at serine residues 118 and 167. • Leptin induces ERE-luciferase activity.

  18. Plasma leptin determination in ruminants: effect of nutritional status and body fatness on plasma leptin concentration assessed by a specific RIA in sheep.

    Science.gov (United States)

    Delavaud, C; Bocquier, F; Chilliard, Y; Keisler, D H; Gertler, A; Kann, G

    2000-05-01

    A specific leptin RIA was developed to assess concentrations of leptin in ovine plasma, and was shown to be efficient with bovine and caprine plasma. A specific, high-affinity antibody was generated against recombinant ovine leptin which, when used in a competitive leptin RIA, provided valid estimates of linearity (r=+0.989-0.998), recovery (102%), repeatability (13%) and limit of sensitivity (0.83 ng/ml for 100 microl sample size). Serial dilutions of five ovine, bovine or caprine plasma samples showed good linearity and parallelism with the recombinant ovine leptin standard curve. A comparison of this RIA was made with a commercial 'multi-species' RIA kit using 56 ovine plasma samples. Major differences were found in assay sensitivity. Non-lactating, non-pregnant, ovariectomized ewes were fed a ration for 65 days which provided 90+/-9% (control; n=12) or 39+/-2% of maintenance energy requirements (underfed; n=16) in order to analyse the respective effects of body fatness (estimated by either an in vivo dilution technique or body condition scoring) and of nutritional status on plasma leptin concentration. There was a significant positive correlation between body fatness or body condition score and plasma leptin levels (r=+0.68, Pnutritional status (17%).

  19. Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production

    Directory of Open Access Journals (Sweden)

    Katriina Vuolteenaho

    2009-01-01

    Full Text Available Obesity is an important risk factor for osteoarthritis (OA in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor κB (NF-κB and mitogen-activated protein kinase (MAPK pathway c-Jun NH2-terminal kinase (JNK. Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

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

    Science.gov (United States)

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

    2014-09-09

    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.

  1. Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women.

    Science.gov (United States)

    Keim, N L; Stern, J S; Havel, P J

    1998-10-01

    On the basis of observations in rodents, leptin is thought to play a key role in the regulation of energy expenditure and food intake, but less is known of its influence on ingestive behavior and energy balance in humans. We examined the effect in women of a chronic energy deficit on plasma leptin concentrations and self-reported appetite and explored possible relations between leptin and appetite sensations. Twelve healthy women (body mass index, in kg/m2: 23-37) participated in a metabolic ward study in which 3 wk of neutral energy balance was followed by 12 wk of energy deficit (energy intake reduced by 2 MJ/d and energy expenditure increased by 0.8 MJ/d). Body weight and composition were monitored, fasting leptin concentrations were measured 4 times, and feelings of hunger, fullness, desire to eat, and prospective consumption were monitored hourly throughout the day on 7 selected days. Adiposity-adjusted leptin decreased by 54% after 1 wk of a moderate energy deficit and remained low after 6 and 12 wk. Leptin was associated with self-reported hunger, desire to eat, and prospective consumption (range of r: -0.6 to -0.7, P percentage drop in circulating leptin and the lowest final leptin concentration. The relation between leptin and hunger was not influenced by amount of weight or body fat loss. These findings support the idea that leptin is a physiologic regulator of hunger during energy deficits in humans; the role of leptin in the long-term regulation of food intake warrants further study.

  2. Relationship between serum leptin and chronic obstructive pulmonary disease in US adults: Results from NHANESIII

    Science.gov (United States)

    Sueblinvong, Viranuj; Liangpunsakul, Suthat

    2014-01-01

    Background Recent studies suggest an important role for leptin in respiratory immune responses and pathogenesis of inflammatory respiratory diseases. There has been an interest to explore if leptin plays any role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Objective We conducted the population-based study to evaluate the relationship between serum leptin and COPD in NHANES III (3rd U.S. National Health and Nutrition Examination Survey participants). Participants and Design 6,415 adults who had fasting serum leptin and underwent spirometry measurement constituted our study group. Main Outcome Measures Serum leptin levels were compared (i) between subjects with normal lung function and those with COPD and (ii) among COPD subjects with different severities. Results Among male participants, 2,257 were controls and 680 had COPD. Compared to controls, COPD subjects were older (62 vs. 43 yrs), had higher prevalence of smokers (78% vs. 58%), lower BMI (26.3 vs. 26.9), and higher serum leptin levels (6.6 vs. 5.9). For female participants, 2,918 were controls and 560 had COPD. Those with COPD were older (60 vs. 43 yrs) and lower BMI (26.9 vs. 27.7). No differences in serum leptin levels were observed. The independent predictors of COPD in both genders were age, BMI, and smoking, but not serum leptin. There were no differences in serum leptin among COPD subjects with different severities. Conclusions We did not find any significant difference in the levels of serum leptin in subjects with COPD. Our data provide indirect evidence against a major role for serum leptin in the pathogenesis of COPD in humans. PMID:25118115

  3. Discovery and characterization of the first genuine avian leptin gene in the rock dove (Columba livia).

    Science.gov (United States)

    Friedman-Einat, Miriam; Cogburn, Larry A; Yosefi, Sara; Hen, Gideon; Shinder, Dmitry; Shirak, Andrey; Seroussi, Eyal

    2014-09-01

    Leptin, the key regulator of mammalian energy balance, has been at the center of a great controversy in avian biology for the last 15 years since initial reports of a putative leptin gene (LEP) in chickens. Here, we characterize a novel LEP in rock dove (Columba livia) with low similarity of the predicted protein sequence (30% identity, 47% similarity) to the human ortholog. Searching the Sequence-Read-Archive database revealed leptin transcripts, in the dove's liver, with 2 noncoding exons preceding 2 coding exons. This unusual 4-exon structure was validated by sequencing of a GC-rich product (76% GC, 721 bp) amplified from liver RNA by RT-PCR. Sequence alignment of the dove leptin with orthologous leptins indicated that it consists of a leader peptide (21 amino acids; aa) followed by the mature protein (160 aa), which has a putative structure typical of 4-helical-bundle cytokines except that it is 12 aa longer than human leptin. Extra residues (10 aa) were located within the loop between 2 5'-helices, interrupting the amino acid motif that is conserved in tetrapods and considered essential for activation of leptin receptor (LEPR) but not for receptor binding per se. Quantitative RT-PCR of 11 tissues showed highest (P < .05) expression of LEP in the dove's liver, whereas the dove LEPR peaked (P < .01) in the pituitary. Both genes were prominently expressed in the gonads and at lower levels in tissues involved in mammalian leptin signaling (adipose; hypothalamus). A bioassay based on activation of the chicken LEPR in vitro showed leptin activity in the dove's circulation, suggesting that dove LEP encodes an active protein, despite the interrupted loop motif. Providing tools to study energy-balance control at an evolutionary perspective, our original demonstration of leptin signaling in dove predicts a more ancient role of leptin in growth and reproduction in birds, rather than appetite control.

  4. Modeling the impact of growth and leptin deficits on the neuronal regulation of blood pressure.

    Science.gov (United States)

    Steinbrekera, Baiba; Roghair, Robert

    2016-11-01

    The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency and aberration in sex hormone levels. As a neurotrophic hormone that is intimately involved in the cardiovascular regulation and whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus a therapeutic agent. As a product of maternal and late fetal adipocytes and the placenta, circulating leptin typically surges late in gestation and declines after delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish the circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation. © 2016 Society for Endocrinology.

  5. Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Zhou Zhou

    2012-12-01

    Full Text Available Abstract Background Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Methods Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells. Results We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3 Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Conclusions Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.

  6. Developmental changes in the relationship between leptin and adiposity among Tsimané children and adolescents.

    Science.gov (United States)

    Sharrock, Katherine C B; Kuzawa, Christopher W; Leonard, William R; Tanner, Susan; Reyes-García, Victoria E; Vadez, Vincent; Huanca, Tomás; McDade, Thomas W

    2008-01-01

    Leptin is thought to signal energy stores, thus helping the body balance energy intake and expenditure. However, the strong relationship between leptin and adiposity in populations with adequate nutrition or common obesity is not universal across ecologic contexts, and leptin often correlates only weakly, or not at all, with adiposity in populations of lean or marginally-nourished males. To clarify whether the relationship between adiposity and leptin changes during development, this study examines leptin and body fat among children and adolescents of lowland Bolivia. Anthropometric measures of body composition and dried blood spot samples were collected from 487 Tsimane' ranging from 2 to 15 years of age. Leptin was assayed using an enzyme immunoassay protocol validated for use with blood spot samples. In this population, leptin concentrations were among the lowest reported in a human population (mean +/- SD: 1.26 +/- 0.5 and 0.57 +/- 0.3 in females and males). In addition, the relationship between leptin and adiposity follows distinct developmental trajectories in males and females. In males, leptin is weakly correlated with most measures of body composition at all ages investigated. However, in females, the level of body fat and the strength of the correlation between body fat and leptin (a measure of its strength as a signal of energy stores) both increase markedly with age. These findings suggest a more important role of leptin as a signal of energy stores among females as they approach reproductive maturity, while raising questions about the function of this hormone in lean males. Copyright 2008 Wiley-Liss, Inc.

  7. Childhood sleep duration and quality in relation to leptin concentration in two cohort studies.

    Science.gov (United States)

    Boeke, Caroline E; Storfer-Isser, Amy; Redline, Susan; Taveras, Elsie M

    2014-03-01

    Poor sleep in childhood is associated with increased obesity risk, possibly by affecting appetite-regulating hormones such as leptin. We examined short- and long-term sleep duration and quality in relation to leptin in two US pediatric cohorts. Analysis of data from two prospective cohort studies. Population-based. Adolescent polysomnography assessments performed in a clinical research unit. Children in Project Viva (n = 655) and adolescents in the Cleveland Children's Sleep & Health Study (n = 502). N/A. In Project Viva, mothers reported average child sleep duration annually from infancy through age 7, and we measured leptin at ages 3 and 7. In the Cleveland Children's Sleep & Health Study, we collected self-reported sleep duration, polysomnography-derived measures of sleep quality, and fasting leptin at ages 16-19. In sex-stratified linear regression analyses adjusted for sociodemographic characteristics and adiposity, chronic curtailed sleep was associated with lower leptin at age 7 in girls; a one-unit decrease in sleep score was associated with a 0.08 decrease in log leptin (95% CI: 0.01,0.15). The association was stronger in girls with greater adiposity (P = 0.01). Among adolescents, shorter sleep was associated with lower leptin in males; each one-hour decrease in sleep duration was associated with a 0.06 decrease in log leptin (95% CI: 0.00, 0.11). Sleep duration was not associated with leptin at other ages. Sleep quality indices were not associated with leptin. Our results suggest possible age-specific sexual dimorphism in the influence of sleep on leptin, which may partly explain inconsistencies in the literature.

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

    Energy Technology Data Exchange (ETDEWEB)

    Das, Suvarthi [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Kumar, Ashutosh [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Seth, Ratanesh Kumar [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States); Tokar, Erik J. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Kadiiska, Maria B. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Waalkes, Michael P. [Inorganic Toxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (United States); Mason, Ronald P. [Free Radical Metabolism Group, Laboratory of Toxicology and Pharmacology, Research Triangle Park, NC 27709 (United States); Chatterjee, Saurabh, E-mail: schatt@mailbox.sc.edu [Environmental Health and Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208 (United States)

    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

  9. Leptin but not Ciliary Neurotrophic Factor (CNTF) induces Phosphotyrosine Phosphatase-1B expression in human neuronal cells (SH-SY5Y): putative explanation of CNTF efficacy in leptin-resistant state

    OpenAIRE

    Benomar, Yacir; Berthou, Flavien; Vacher, Claire-Marie; Bailleux, Virginie; Gertler, Arieh; Djiane, Jean; Taouis, Mohammed

    2009-01-01

    Growing evidences suggest that obesity is associated with hypothalamic leptin resistance, leading to the alteration of food intake control. Alternative treatment using ciliary neurotrophic factor (CNTF) has been suggested because CNTF exerts a leptin-like effect, even in leptin-resistant states, but the mechanisms by which CNTF maintains this effect are not yet understood. Both leptin and CNTF act in the hypothalamus through similar signaling pathways including janus kinase-2/signal transduce...

  10. Association of Plasma Leptin Levels With Maternal Body Weight and Body Mass Index in Premature and Term Newborns

    Directory of Open Access Journals (Sweden)

    Shih-Ping Ho

    2010-02-01

    Conclusion: Neonatal serum leptin concentrations within 24 hours of birth correlated with maternal body weight and BMI, especially in premature newborns. Premature newborns had significantly lower leptin levels than full-term newborns.

  11. Effects of dopamine on leptin release and leptin gene (OB expression in adipocytes from obese and hypertensive patients

    Directory of Open Access Journals (Sweden)

    Alvarez-Aguilar C

    2013-11-01

    Full Text Available Cleto Alvarez-Aguilar,1–3 Alfonso Rafael Alvarez-Paredes,2 Bengt Lindholm,4 Peter Stenvinkel,4 Elvia García-López,4 Oliva Mejía-Rodríguez,5 Joel Edmundo López-Meza,6 Dante Amato,7 Ramon Paniagua8 1Hospital General Regional N°1, Instituto Mexicano del Seguro Social (IMSS, Morelia, 2Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez" Universidad Michoacana de San Nicolás de Hidalgo (UMSNH, Morelia, Michoacán, 3División de Estudios Superiores, Universidad Nacional Autónoma de México (UNAM, México DF, México; 4Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; 5Coordinación Delegacional de Investigación en Salud, IMSS, Morelia, 6Centro Multidisciplinario de Estudios en Biotecnología (CMEB, UMSNH, Morelia, Michoacán, 7Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, 8Unidad de Investigación en Enfermedades Nefrológicas, Hospital de Especialidades, CMN Siglo XXI, IMSS, México DF, México Background: A reduction of dopaminergic (DAergic activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE, and prolactin on leptin release and leptin gene (OB expression in adipocytes from obese and hypertensive patients. Methods: Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 µmol/L, NE (1.0 µmol/L, insulin (0.1 µmol/L, and prolactin (1.0 µmol/L, and from five nonobese and normotensive controls treated with DA (1 µmol/L, NE (1 µmol/L, insulin (0.1 µmol/L, and prolactin (1.0 µmol/L. Results: A dose-related reduction of leptin release and OB

  12. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen

    Science.gov (United States)

    Shi, Zhigang; Brooks, Virginia L

    2015-01-01

    Key points Leptin increases sympathetic nerve activity (SNA) in males, which contributes to obesity-induced hypertension; however, whether leptin is equally effective in females is unknown. We report that leptin does increase SNA and heart rate in female rats; however, for lumbar and renal SNA, this action is only evident in pro-oestrus and in oestrogen-treated ovariectomized rats, but not in ovariectomized or dioestrus rats. Leptin increases SNA and heart rate similarly in male and pro-oestrus female rats; however, leptin increases arterial pressure only in males. Blockade of MC3/4 receptors in the paraventricular nucleus (PVN) with SHU9119 decreases SNA in leptin-treated pro-oestrus rats, suggesting that leptin increases SNA in part by increasing α-melanocyte-stimulating hormone drive of PVN presympathetic neurons. Our data establish sex differences in leptin's effects to increase SNA and arterial pressure, which emphasizes the need for enhanced recognition and investigation of sex differences in obesity-induced sympathoexcitation and hypertension. Abstract Obesity and hypertension are commonly associated, and activation of the sympathetic nervous system is considered to be a major contributor, at least in part due to the central actions of leptin. However, while leptin increases sympathetic nerve activity (SNA) in males, whether leptin is equally effective in females is unknown. Here, we show that intracerebroventricular (i.c.v.) leptin increases lumbar (LSNA) and renal (RSNA) SNA and baroreflex control of LSNA and RSNA in α-chloralose anaesthetized female rats, but only during pro-oestrus. In contrast, i.c.v. leptin increased basal and baroreflex control of splanchnic SNA (SSNA) and heart rate (HR) in rats in both the pro-oestrus and dioestrus states. The effects of leptin on basal LSNA, RSNA, SSNA and HR were similar in males and pro-oestrus females; however, i.c.v. leptin increased mean arterial pressure (MAP) only in males. Leptin did not alter LSNA or HR

  13. The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus

    Directory of Open Access Journals (Sweden)

    Huixian Zhang

    2016-10-01

    Full Text Available Leptin is an essential hormone for the regulation of energy metabolism and food intake in vertebrate animals. To better understand the physiological roles of leptin in nutrient regulation in paternal ovoviviparous fish (family Syngnathidae, the present study cloned the full-length of leptin-a and leptin receptor (lepr genes in lined seahorse (Hippocampus erectus. Results showed that there was a 576-bp intron between two exons in leptin-a gene but no leptin-b gene in seahorse. Although the primary amino acid sequence conservation of seahorse leptin-a was very low, the 3-D structure modeling of seahorse leptin-a revealed strong conservation of tertiary structure with other vertebrates. Seahorse leptin-a mRNA was highly expressed in brain, whereas lepr mRNA was mainly expressed in ovary and gill. Interestingly, both leptin-a and lepr mRNA were expressed in the brood pouch of male seahorse, suggesting the leptin system plays a role during the male pregnancy. Physiological experiments showed that the expression of hepatic leptin-a and lepr mRNA in unfed seahorses was significantly higher than that in those fed 100%, as well as 60%, of their food during the fasting stage, showing that seahorse might initiate the leptin system to regulate its energy metabolism while starving. Moreover, the expression of leptin-a in the brood pouch of pregnant seahorse was significantly upregulated compared with non-pregnant seahorse, whereas the expression of lepr was downregulated, suggesting that the leptin system might be involved in the male pregnancy. In conclusion, the leptin system plays a role in the energy metabolism and food intake, and might provide new insights into molecular regulation of male pregnancy in seahorse.

  14. Association between plasma leptin and blood pressure in two population-based samples of children and adolescents

    DEFF Research Database (Denmark)

    Grøntved, Anders; Steene-Johannessen, Jostein; Kynde, Iben

    2011-01-01

    In this study we examined the association between leptin and blood pressure in a population-based study of Danish and Norwegian children and adolescents. Because of the putative bidirectional relationship between leptin and adiposity we formally tested (i) the mediating effect of body mass index...... in the association between leptin and blood pressure, and (ii) the mediating effect of leptin in the association between body mass index and blood pressure....

  15. The Beneficial Effects of Leptin on REM Sleep Deprivation-Induced Cognitive Deficits in Mice

    Science.gov (United States)

    Chang, Hsiao-Fu; Su, Chun-Lin; Chang, Chih-Hua; Chen, Yu-Wen; Gean, Po-Wu

    2013-01-01

    Leptin, a 167 amino acid peptide, is synthesized predominantly in the adipose tissues and plays a key role in the regulation of food intake and body weight. Recent studies indicate that leptin receptor is expressed with high levels in many brain regions that may regulate synaptic plasticity. Here we show that deprivation of rapid eye movement…

  16. Mechanism of protein tyrosine phosphatase 1B-mediated inhibition of leptin signalling

    DEFF Research Database (Denmark)

    Lund, I K; Hansen, J A; Andersen, H S

    2005-01-01

    Upon leptin binding, the leptin receptor is activated, leading to stimulation of the JAK/STAT signal transduction cascade. The transient character of the tyrosine phosphorylation of JAK2 and STAT3 suggests the involvement of protein tyrosine phosphatases (PTPs) as negative regulators of this sign...

  17. Leptin, abdominal obesity, and onset of depression in older men and women

    NARCIS (Netherlands)

    Milaneschi, Y.; Simonsick, E.M.; Vogelzangs, N.; Strotmeyer, E.S.; Yaffe, K.; Harris, T.B.; Tolea, M.I.; Ferrucci, L.; Penninx, B.W.J.H.

    2012-01-01

    Objective: The mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the "leptin hypothesis" of depression suggests that leptin resistance may be involved in mood regulation. We tested whether high circulatory concentration of

  18. Positive association of plasma leptin with sleep quality in obese type 2 diabetes patients.

    Science.gov (United States)

    Hirota, Tomoe; Morioka, Tomoaki; Yoda, Koichiro; Toi, Norikazu; Hayashi, Noriyuki; Maruo, Saori; Yamazaki, Yuko; Kurajoh, Masafumi; Motoyama, Koka; Yamada, Shinsuke; Shoji, Tetsuo; Emoto, Masanori; Inaba, Masaaki

    2018-02-26

    Poor sleep quality is associated with obesity and diabetes. The adipocyte-derived hormone, leptin, was recently shown to underlie the link between abnormal sleep and obesity. We aimed to investigate the association between leptin and sleep quality in type 2 diabetes patients. In the present cross-sectional study, we studied 182 type 2 diabetes patients, among whom 113 were diagnosed with obesity (body mass index ≥25 kg/m 2 ). Fasting plasma leptin levels were measured, and sleep architecture was assessed using single-channel electroencephalography. Using unadjusted analyses, the obese type 2 diabetes patients, but not their non-obese counterparts, showed a positive correlation between plasma leptin levels and a parameter for deep sleep assessed by delta power during the first sleep cycle. Multivariate analysis showed that plasma leptin levels were positively associated with delta power, but not with the total sleep time, after adjusting for potential confounders including age, body mass index and the apnea-hypopnea index, in the obesity group. However, neither delta power nor total sleep time was associated with leptin in the non-obesity group. Plasma leptin levels are independently associated with sleep quality in obese, but not in non-obese, type 2 diabetes patients. The present study indicates a favorable relationship between leptin and sleep quality in obese type 2 diabetes patients. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  19. Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity

    DEFF Research Database (Denmark)

    Verdich, C; Toubro, S; Buemann, B

    2001-01-01

    To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate...... oxidations, and SPA as predictive markers of success during a standardized weight loss intervention....

  20. Study on the relationship between serum leptin level and ischemic cerebrovascular disease (ICVD)

    International Nuclear Information System (INIS)

    Luo Nanping; Hu Chengjing; Wang Ruishan; Yin Qiuxia; Niu Aijun; Xue Lian; Xue Shenwu; Chen Qing

    2004-01-01

    Objective: To investigate the inter-relationship among serum leptin insulin resistance and blood lipids, and to explore the role of leptin in the pathogenesis of ischemic cerebrovascular diseases (ICVD). Methods: Levels of serum leptin, insulin and blood lipids were determined with RIA in 131 patients with different types of ICVD and 36 controls. Results: The levels of serum leptin in ICVD patients were significantly higher than those in the controls (P<0.01). Changes of blood lipids and insulin paralleled those of leptin (cxcept with HDL-C). The serum leptin were positively correlated to cholesterol, TG and insulin levels (r=0.45, P<0.05; r=0.31, P<0.05, r=0.55, P<0.01), but negatively correlated to HDL-C (r=-0.88, P<0.05). Conclusion: The high expression of leptin in ICVD patients is associated with high lipid and insulin levels. The close relationship among them indicates that high leptin levels play an important role in the pathogenesis of metabolic syndrome as well as atheromatous cerebrovascular diseases. (authors)

  1. Purifying selection on leptin genes in teleosts may be due to ...

    Indian Academy of Sciences (India)

    Table 1. Organisms and accession numbers of the Leptin cDNA sequences used in this paper. Species. Gene. Accession. Leptin. NM_001095714.1. Amphibian. Xenopus tropicalis. Mammal. Felis catus. Rattus norvegicus. Homo sapiens. Mus musculus. Oryctolagus cuniculus. Sus scrofa. Macaca mulatta. Canis lupus ...

  2. Leptin levels are associated with fat oxidation and dietary-induced weight loss in obesity

    DEFF Research Database (Denmark)

    Verdich, C; Toubro, S; Buemann, B

    2001-01-01

    To examine the relationship between fasting plasma leptin and 24-hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate ox...... oxidations, and SPA as predictive markers of success during a standardized weight loss intervention....

  3. Reference values for serum leptin in healthy non-obese children and adolescents

    DEFF Research Database (Denmark)

    Lausten-Thomsen, Ulrik; Christiansen, Michael; Hedley, Paula Louise

    2016-01-01

    . Methods: A total of 1193 healthy, non-obese Danish schoolchildren (730 girls, 463 boys) aged 6–18 years (median 11.9) were examined by trained medical staff. Serum leptin and sOB-R concentrations in venous fasting blood samples were quantitated by immunoassay. Percentile curves of leptin, sOB-R, and free...

  4. Mechanism for leptin's acute insulin-independent effect to reverse diabetic ketoacidosis.

    Science.gov (United States)

    Perry, Rachel J; Peng, Liang; Abulizi, Abudukadier; Kennedy, Lynn; Cline, Gary W; Shulman, Gerald I

    2017-02-01

    The mechanism by which leptin reverses diabetic ketoacidosis (DKA) is unknown. We examined the acute insulin-independent effects of leptin replacement therapy in a streptozotocin-induced rat model of DKA. Leptin infusion reduced rates of lipolysis, hepatic glucose production (HGP), and hepatic ketogenesis by 50% within 6 hours and were independent of any changes in plasma glucagon concentrations; these effects were abrogated by coinfusion of corticosterone. Treating leptin- and corticosterone-infused rats with an adipose triglyceride lipase inhibitor blocked corticosterone-induced increases in plasma glucose concentrations and rates of HGP and ketogenesis. Similarly, adrenalectomized type 1 diabetic (T1D) rats exhibited decreased rates of lipolysis, HGP, and ketogenesis; these effects were reversed by corticosterone infusion. Leptin-induced decreases in lipolysis, HGP, and ketogenesis in DKA were also nullified by relatively small increases (15 to 70 pM) in plasma insulin concentrations. In contrast, the chronic glucose-lowering effect of leptin in a STZ-induced mouse model of poorly controlled T1D was associated with decreased food intake, reduced plasma glucagon and corticosterone concentrations, and decreased ectopic lipid (triacylglycerol/diacylglycerol) content in liver and muscle. Collectively, these studies demonstrate marked differences in the acute insulin-independent effects by which leptin reverses fasting hyperglycemia and ketoacidosis in a rodent model of DKA versus the chronic pleotropic effects by which leptin reverses hyperglycemia in a non-DKA rodent model of T1D.

  5. What fans the fire: insights into mechanisms of leptin in metabolic syndrome-associated heart diseases.

    Science.gov (United States)

    Dong, Maolong; Ren, Jun

    2014-01-01

    Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.

  6. Effects of weight loss on leptin, sex hormones, and measures of adiposity in obese children.

    Science.gov (United States)

    Sudi, K M; Gallistl, S; Borkenstein, M H; Payerl, D; Aigner, R; Möller, R; Tafeit, E

    2001-04-01

    Adipose tissue influences steroid conversion by paracrine and autocrine mechanisms. Leptin is secreted by adipocytes and influenced by sex hormones and adiposity. Short-term weight loss in the treatment of childhood obesity reduces leptin and adipose tissue. We therefore asked, Do alterations in sex hormones occur owing to weight loss? and can these alterations be explained by changes in fat mass or sc fat and are alterations in sex hormones directly related to the fall in leptin? Twenty obese boys and 40 obese girls were studied before and after 3 wk of low-calorie diet and physical activity. The weight loss program significantly lowered fat mass, abdominal fat distribution, sc fat (all p testosterone. Changes in leptin were related to changes in body mass and to changes in fat mass in boys. In girls, changes in leptin were related to changes in sc fatness and also to changes in insulin. In boys, the reduction in sc fat was positively correlated to changes in testosterone (r = 0.54; p testosterone (r = 0.33; p fat depots in boys whereas in girls changes in insulin might participate in changes in sex hormones. A greater fall in leptin owing to short-term weight loss is not associated with greater alterations in sex hormones and initial leptin is the best determinant to explain the variability in changes in leptin. The possibility of sex differences in changes in sex hormones secondary to the reduction in fatness warrants further study.

  7. Leptin as a Marker of Body Fat and Hyperinsulinemia in College Students

    Science.gov (United States)

    Kempf, Angela M.; Strother, Myra L.; Li, Chaoyang; Kaur, Harsohena; Huang, Terry T-K.

    2006-01-01

    Little is known about obesity and insulin resistance in college students. Leptin is a hormone secreted by fat cells and has been shown to strongly correlate with both obesity and insulin resistance in children and adults. We investigated associations of leptin with insulin secretion and action in 119 normal-weight students aged 18-24 years. Leptin…

  8. Measurement of serum leptin levels in polycystic ovary syndrome with hyperandrogenemia and its significance

    International Nuclear Information System (INIS)

    Wang Yande; Zhang Zhiping; Lu Gen; Luo Beilei

    2002-01-01

    Objective: To investigate the serum leptin concentration in polycystic ovary syndrome (PCOS) with hyperandrogenemia (HA) and its relationship with testosterone (T) level and body mass index (BMI). Methods: Serum leptin levels were measured by radioimmunoassay in 53 patients with PCOS, in which 36 cases were of the in non-obesity group and 17 cases in obese group. 30 non-obese cases and 20 obese cases without PCOS served as controls. Results: The levels of leptin in PCOS with HA in obese and non-obese group were significantly higher than those in control group (all p < 0.01). There was a positive correlation between serum leptin levels and testosterone levels in both groups (r = 0.51, p < 0.01 and r = 0.58, p < 0.01). No correlation existed between serum leptin levels and body mass index (BMI) in PCOS patients of non-obese group but there was positive correlation in obesity group (r = 0.56, p < 0.01). Conclusion: High serum leptin levels is one of the characteristic in PCOS patients. The HA in PCOS patients is related to serum leptin levels and heavyweight or obese patients have the phenomenon of leptin resistance

  9. Energy budget, behavior and leptin in striped hamsters subjected to food restriction and refeeding.

    Directory of Open Access Journals (Sweden)

    Zhi-Jun Zhao

    Full Text Available Food restriction induces a loss of body mass that is often followed by rapid regaining of the lost weight when the restriction ends, consequently increasing a risk of development of obesity. To determine the physiological and behavioral mechanisms underlining the regaining, striped hamsters were restricted to 85% of initial food intake for 4 weeks and refed ad libitum for another 4 weeks. Changes in body mass, energy budget, activity, body composition and serum leptin level were measured. Body mass, body fat mass and serum leptin level significantly decreased in food-restricted hamsters, and increased when the restriction ended, showing a short "compensatory growth" rather than over-weight or obesity compared with ad libitum controls. During restriction, the time spent on activity increased significantly, which was opposite to the changes in serum leptin level. Food intake increased shortly during refeeding, which perhaps contributed to the rapid regaining of body mass. No correlation was observed between serum leptin and energy intake, while negative correlations were found in hamsters that were refed for 7 and 28 days. Exogenous leptin significantly decreased the time spent on activity during food restriction and attenuated the increase in food intake during refeeding. This suggests that low leptin in restricted animals may function as a starvation signal to induce an increase in activity behavior, and high leptin likely serves as a satiety signal to prevent activity during refeeding. Leptin may play a crucial role in controlling food intake when the restriction ends, and consequently preventing overweight.

  10. Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

    DEFF Research Database (Denmark)

    Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I.

    2016-01-01

    In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic ...

  11. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

    DEFF Research Database (Denmark)

    Donahue, R P; Prineas, R J; Donahue, R D

    1999-01-01

    Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic m...

  12. An age-dependent interaction with leptin unmasks ghrelin's bone-protective effects

    Science.gov (United States)

    The mutual interplay between energy homeostasis and bone metabolism is an important emerging concept. Ghrelin and leptin antagonize each other in regulating energy balance, but the role of this interaction in bone metabolism is unknown. Using ghrelin receptor and leptin-deficient mice, we show that ...

  13. Low Leptin Availability as a Risk Factor for Dementia in Chilean Older People

    Directory of Open Access Journals (Sweden)

    Cecilia Albala

    2016-07-01

    Full Text Available Objective: The aim was to study the role of leptin in the development of dementia. Methods: Follow-up of the ALEXANDROS cohorts, with baseline measurements in 2000. From 1,136 available subjects free of dementia at baseline, 667 subjects had frozen baseline blood samples for measuring leptin and soluble leptin receptor (sOB-R. The free leptin index (FLI was calculated as the ratio of leptin to sOB-R. Dementia was defined as an MMSE score 5 in the Pfeffer Activities Questionnaire. Results: After 15 years of follow-up, 42 incident cases of dementia were identified. No difference in serum leptin was observed between people with and without dementia, but sOB-R was higher in demented than in nondemented subjects (sOB-R: 44.94 ± 23.97 vs. 33.73 ± 21.13 ng/ml. The adjusted risk for dementia increased, the higher the log sOB (hazard ratio = 3.58; 95% CI 1.72-7.45, p = 0.001. Conclusion: Lower availability of free leptin was found in demented than in nondemented people, suggesting a role of leptin in cognition.

  14. Interrelationships of Maternal Serum Leptin, Body Mass Index and Gestational Age

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    Ming-Jie Yang

    2005-10-01

    Conclusion: Maternal serum leptin concentration was significantly related to gestational age (except in the first trimester and BMI in the 3 trimesters and throughout pregnancy. Serum leptin concentration peaked during the early third trimester and declined significantly thereafter. Maternal BMI was related to gestational age in the second trimester and the whole pregnancy.

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

    Science.gov (United States)

    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…

  16. Leptin and regulatory T-lymphocytes in idiopathic pulmonary arterial hypertension.

    Science.gov (United States)

    Huertas, Alice; Tu, Ly; Gambaryan, Natalia; Girerd, Barbara; Perros, Frédéric; Montani, David; Fabre, Dominique; Fadel, Elie; Eddahibi, Saadia; Cohen-Kaminsky, Sylvia; Guignabert, Christophe; Humbert, Marc

    2012-10-01

    Immune mechanisms and autoimmunity seem to play a significant role in idiopathic pulmonary arterial hypertension (IPAH) pathogenesis and/or progression, but the pathophysiology is still unclear. Recent evidence has demonstrated a detrimental involvement of leptin in promoting various autoimmune diseases by controlling regulatory T-lymphocytes. Despite this knowledge, the role of leptin in IPAH is currently unknown. We hypothesised that leptin, synthesised by dysfunctional pulmonary endothelium, might play a role in the immunopathogenesis of IPAH by regulating circulating regulatory T-lymphocytes function. First, we collected serum and regulatory T-lymphocytes from controls, and IPAH and scleroderma-associated pulmonary arterial hypertension (SSc-PAH) patients; secondly, we recovered tissue samples and cultured endothelial cells after either surgery or transplantation in controls and IPAH patients, respectively. Our findings indicate that serum leptin was higher in IPAH and SSc-PAH patients than controls. Circulating regulatory T-lymphocyte numbers were comparable in all groups, and the percentage of those expressing leptin receptor was higher in IPAH and SSc-PAH compared with controls, whereas their function was reduced in IPAH and SSc-PAH patients compared with controls, in a leptin-dependent manner. Furthermore, endothelial cells from IPAH patients synthesised more leptin than controls. Our data suggest that endothelial-derived leptin may play a role in the immunopathogenesis of IPAH.

  17. Neuroprotective effects of leptin in the context of obesity and metabolic disorders.

    Science.gov (United States)

    Davis, Cecilia; Mudd, Jeremy; Hawkins, Meredith

    2014-12-01

    As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. NPY-leptin : opposing effects on appetitive and consummatory ingestive behavior and sexual behavior

    NARCIS (Netherlands)

    Ammar, AA; Sederholm, F; Saito, TR; Scheurink, AJW; Johnson, AE; Södersten, P.

    Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 mu g) stimulated and leptin (10 mu g) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a

  19. Metabolic Risk Susceptibility in Men Is Partially Related to Adiponectin/Leptin Ratio

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    Gloria Lena Vega

    2013-01-01

    Full Text Available Background. High adiponectin/leptin ratio may be protective from metabolic risks imparted by high triglyceride, low HDL, and insulin resistance. Methods. This cross-sectional study examines plasma adipokine levels in 428 adult men who were subgrouped according to low (<6.5 μg/mLand high (≥6.5 μg/mLadiponectin levels or a low or high ratio of adiponectin/leptin. Results. Men with high adiponectin/leptin ratio had lower plasma triglyceride and higher HDL cholesterol than those with low ratio. Similarly, those with high adiponectin/leptin ratio had lower TG/HDL cholesterol ratio and HOMA2-IR than those with low ratio. In contrast, levels of adiponectin or the ratio of adiponectin/leptin did not associate with systolic blood pressure. But the ratio of adiponectin/leptin decreased progressively with the increase in the number of risk factors for metabolic syndrome. Conclusion. Adipokine levels may reflect adipose tissue triglyceride storage capacity and insulin sensitivity. Leptin is an index of fat mass, and adiponectin is a biomarker of triglyceride metabolism and insulin sensitivity. Men with high adiponectin/leptin ratios have better triglyceride profile and insulin sensitivity than men with a low ratio regardless of waist girth.

  20. Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study

    DEFF Research Database (Denmark)

    Donahue, R P; Prineas, R J; Donahue, R D

    1999-01-01

    Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men...

  1. Feeding and temperature responses to intravenous leptin infusion are differential predictors of obesity in rats

    NARCIS (Netherlands)

    Ruffin, M.; Adage, T; Kuipers, F; Strubbe, J H; Scheurink, A J W; van Dijk, G; Ruffin, Marie-Pierre

    2004-01-01

    Obesity is frequently associated with leptin resistance. The present study investigated whether leptin resistance in rats is present before obesity develops, and thus could underlie obesity induced by 16 wk exposure to a liquid, palatable, high-energy diet (HED). Before HED exposure, male Wistar

  2. Leptin hormone in obese and non-obese stable and exacerbated cases of chronic obstructive pulmonary disease

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    Ahmad Elsayed Mahmoud

    2015-07-01

    Conclusion: Serum leptin hormone level (ng/ml was significantly higher in obese COPD cases than in controls and non-obese cases and during exacerbation than in stability which indicates that leptin plays a role in the systemic inflammatory process. Serum leptin hormone level positively correlated with BMI (kg/m2.

  3. Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study

    NARCIS (Netherlands)

    Ruige, J B; Dekker, J M; Blum, W F; Stehouwer, C D; Nijpels, G; Mooy, J; Kostense, P J; Bouter, L M; Heine, R J

    OBJECTIVE: Leptin is thought to play a key role in the control of body weight. There is a complex interrelationship between leptin and insulin or insulin resistance, but it is unknown how leptin is regulated. We therefore explored, in a large population-based study of 2,484 Caucasian subjects aged

  4. Increased leptin expression in common Carp (Cyprinus carpio) after food intake but not after fasting or feeding to satiation

    NARCIS (Netherlands)

    Huising, M.O.; Geven, E.J.W.; Kruiswijk, C.P.; Nabuurs, S.B.; Stolte, E.H.; Spanings, F.A.T.; Verburg-van Kemenade, B.M.L.; Flik, G.

    2006-01-01

    Leptin is a key factor in the regulation of food intake and is an important factor in the pathophysiology of obesity. However, more than a decade after the discovery of leptin in mouse, information regarding leptin in any nonmammalian species is still scant. We report the identification of duplicate

  5. Increased leptin expression in common carp (Cyprinus carpio) after food intake but not after fasting or feeding to satiation

    NARCIS (Netherlands)

    Huising, M.O.; Geven, E.J.; Kruiswijk, C.P.; Nabuurs, S.B.; Stolte, H.H.; Spanings, F.A.; Verburg-van Kemenade, B.M.L.; Flik, G.

    2006-01-01

    Leptin is a key factor in the regulation of food intake and is an important factor in the pathophysiology of obesity. However, more than a decade after the discovery of leptin in mouse, information regarding leptin in any nonmammalian species is still scant. We report the identification of duplicate

  6. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

    Directory of Open Access Journals (Sweden)

    Lerario D.D.G.

    2001-01-01

    Full Text Available The adipocyte hormone leptin is thought to serve as a signal to the central nervous system reflecting the status of fat stores. Serum leptin levels and adipocyte leptin messenger RNA levels are clearly increased in obesity. Nevertheless, the factors regulating leptin production are not fully understood. The aim of this study was to determine the effects of in vivo administration of the synthetic glucocorticoid dexamethasone and weight loss on serum leptin levels in two independent protocols. Twenty-five obese subjects were studied (18 women and 7 men, mean age 26.6 ± 6 years, BMI 31.1 ± 2.5 kg/m², %fat 40.3 ± 8.3 and compared at baseline to 22 healthy individuals. Serum levels of leptin, insulin, proinsulin and glucose were assessed at baseline and after ingestion of dexamethasone, 4 mg per day (2 mg, twice daily for two consecutive days. To study the effects of weight loss on serum leptin, 17 of the obese subjects were submitted to a low-calorie dietary intervention trial for 8 weeks and again blood samples were collected. Serum leptin levels were significantly higher in the obese group compared to the control group and a high positive correlation between leptinemia and the magnitude of fat mass was found (r = 0.88, P<0.0001. After dexamethasone, there was a significant increase in serum leptin levels (22.9 ± 12.3 vs 51.4 ± 23.3 ng/ml, P<0.05. Weight loss (86.1 ± 15.1 vs 80.6 ± 14.2 kg, P<0.05 led to a reduction in leptin levels (25.13 ± 12.8 vs 15.9 ± 9.1 ng/ml, P<0.05. We conclude that serum leptin levels are primordially dependent on fat mass magnitude. Glucocorticoids at supraphysiologic levels are potent secretagogues of leptin in obese subjects and a mild fat mass reduction leads to a disproportionate decrease in serum leptin levels. This suggests that, in addition to the changes in fat mass, complex nutritional and hormonal interactions may also play an important role in the regulation of leptin levels.

  7. Gender differences of cannabis smoking on serum leptin levels: population-based study

    Directory of Open Access Journals (Sweden)

    Fernanda P. Moreira

    2018-02-01

    Full Text Available Objective: To evaluate the serum leptin levels in cannabis smokers. Methods: This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Results: Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008. When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039. Conclusion: Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.

  8. Gender differences of cannabis smoking on serum leptin levels: population-based study.

    Science.gov (United States)

    Moreira, Fernanda P; Wiener, Carolina D; Oliveira, Jacqueline F de; Souza, Luciano D M; da Silva, Ricardo A; Portela, Luis V; Lara, Diogo R; Jansen, Karen; Oses, Jean Pierre

    2018-02-01

    To evaluate the serum leptin levels in cannabis smokers. This was a cross-sectional population-based study of participants between the ages of 18 and 35 years. The data were collected through a self-administered questionnaire covering sociodemographic data and the use of psychoactive substances. Leptin levels were measured using a commercial ELISA kit. Of the 911 participants, 6.7% were identified as cannabis smokers and had significantly lower leptin levels (p = 0.008). When stratified by gender, there was a significant decrease in leptin levels among male smokers (p = 0.039). Cannabis smoking was linked to leptin levels in men, suggesting that the response to biological signals may be different between men and women.

  9. Serum Leptin Concentrations during the Menstrual Cycle in Iranian Healthy Women

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    Nahid Einollahi

    2010-10-01

    Full Text Available Leptin, a circulating 16-kd polypeptide consisting of 167 amino acids, appears to be involved in the body weight homeostasis. Moreover leptin plays an important role for the reproductive system, early embryogenesis, and fat metabolism during pregnancy and puberty. Significant correlations have been found between leptin and sexual hormones, which is a cytokine and has hormonal properties. The aim of this study was to determine serum leptin levels during the menstrual cycle, and the association between serum leptin and reproductive hormones in young, healthy Iranian women. 42 healthy women volunteered for the study. They all had regular menstrual cycles, with cycle length varying between 26 and 32 days. None of them used oral contraceptives. All were of normal weight, with body mass index ( BMI

  10. Psychobiology of purging disorder: reduction in circulating leptin levels in purging disorder in comparison with controls.

    Science.gov (United States)

    Jimerson, David C; Wolfe, Barbara E; Carroll, Devon P; Keel, Pamela K

    2010-11-01

    Purging disorder (PD), a recently recognized eating disorder syndrome, is differentiated from bulimia nervosa (BN) based on the absence of objectively large binge episodes. BN has been associated with low serum leptin levels. This study examined whether PD is also characterized by low serum leptin. Participants included women with PD (n = 20) or BN (n = 37), and non-eating disorder controls (n = 33). Blood samples for measurement of leptin and total ghrelin were obtained after overnight fast. In comparison with control values, leptin levels were significantly decreased in PD (p < .01), as well as in BN (p < .02). Plasma ghrelin levels did not differ significantly across groups. These results provide the first evidence that PD is associated with alteration in a neurobiological pathway influencing eating patterns and body weight. Further research is needed to assess whether low leptin levels in PD and BN are associated with restrained eating and weight suppression. © 2009 by Wiley Periodicals, Inc.

  11. Detection of leptin in serum from patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chu Yongli; Sun Yongyu; Qiu Hongyu

    2002-01-01

    Objective: To investigate the relationship between leptin and insulin resistance in polycystic ovary syndrome (PCOS). Methods: Blood samples for leptin, LH/FSH, fasting insulin and glucose measurement from 17 patients with PCOS and 20 cases as control group were analyzed by radioimmunoassay or oxidase test. Results: It showed that leptin, LH/FSH levels of serum, insulin resistant index (IRI) and body mass index (BMI) in patients with PCOS were significantly higher than that in the control group (P<0.05). Leptin level was positively related with IRI and LH/FSH and BMI (P<0.01, P<0.05, P<0.01). Conclusion: It was suspected that leptin accelerate insulin resistance, the interaction of two factors aggravate the change of pathophysiology in PCOS

  12. Leptin Involvement in Primary Brain and Pituitary Tumors: Therapeutic Potential, Prognostic Value, and Proposed Diagnostic Application.

    Science.gov (United States)

    Bikis, Christos; Tzanavari, Theodora; Alexandraki, Krystallenia I; Theocharis, Stamatios

    2018-02-20

    Brain tumors are associated with increased mortality and morbidity and are the most common cancer type in children and young adults. The present review focuses on the interplay between leptin, the most extensively studied adipokine, and the onset, development, and treatment of primary brain and intracranial tumors. The two main mechanisms for increased leptin levels in intracranial tumor survivors, leptin resistance caused by hypothalamic damage, or secondary to obesity, are discussed. The contradicting mechanistic observations on leptin being able to both promote tumorinogenesis (e.g., in gliomas) as well as inhibit it (e.g., in adenomas) are also reported. Additionally, the relevant current and future clinical applications, including most notably the proposed use of serum leptin measurements for non-invasive brain tumor diagnostics, are also reported.

  13. Effects of Metformin on Serum Levels of Secreted Klotho and Leptin in PCOS Women

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    Savadali Saifi Novashnag

    2016-07-01

    Patients’ weights showed some decline. Fasting plasma glucose levels and insulin resistance decreased significantly (p<0.01. Hormonal assays indicated significant decrease in leptin and insulin levels and rise in Klotho levels. BMIs did not change meaningfully. Measurements of leptin and klotho levels showed a decrease in mean leptin levels from 34.74 to 28.41 ng/l and the level of klotho increased from 4.01 to 5.43 ng/l. Conclusion: This study showed that metformin treatment can cause a rise in klotho and a decrease in leptin levels without considerable effects on the weights of women with PCOS. Probably, leptin exerts its physiological effects in low concentrations while klotho in contrast acts physiologically in higher concentrations.

  14. SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

    Science.gov (United States)

    Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

    2016-01-01

    Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

  15. Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin

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    Ji Chen

    2018-03-01

    Full Text Available Growth and reproduction are closely related. Growth hormone (GH-transgenic common carp exhibit accelerated growth and delayed reproductive development, which provides an amenable model to study hormone cross talk between the growth and reproductive axes. We analyzed the energy status and reproductive development in GH-transgenic common carp by using multi-tissue RNA sequencing, real-time-PCR, Western blotting, ELISA, immunofluorescence, and in vitro incubation. The expression of gys (glycogen synthase and igfbp1 (insulin-like growth factor binding protein as well as blood glucose concentrations are lower in GH-transgenic carp. Agrp1 (agouti-related protein 1 and sla (somatolactin a, which are related to appetite and lipid catabolism, are significantly higher in GH-transgenic carp. Low glucose content and increased appetite indicate disrupted metabolic and energy deprivation status in GH-transgenic carp. Meanwhile, the expression of genes, such as gnrhr2 (gonadotropin-releasing hormone receptor 2, gthα (gonadotropin hormone, alpha polypeptide, fshβ (follicle stimulating hormone, beta polypeptide, lhβ [luteinizing hormone, beta polypeptide] in the pituitary, cyp19a1a (aromatase A in the gonad, and cyp19a1b (aromatase B in the hypothalamus, are decreased in GH-transgenic carp. In contrast, pituitary gnih (gonadotropin inhibitory hormone, drd1 (dopamine receptor D1, drd3 (dopamine receptor D3, and drd4 (dopamine receptor D4 exhibit increased expression, which were associated with the retarded reproductive development. Leptin receptor mRNA was detected by fluorescence in situ hybridization in the pituitary including the pars intermedia and proximal pars distalis, suggesting a direct effect of leptin on LH. Recombinant carp Leptin protein was shown to stimulate pituitary gthα, fshβ, lhβ expression, and ovarian germinal vesicle breakdown in vitro. In addition to neuroendocrine factors, we suggest that reduced hepatic leptin signaling to the

  16. Leptin receptor expressing neurons express phosphodiesterase-3B (PDE3B) and leptin induces STAT3 activation in PDE3B neurons in the mouse hypothalamus.

    Science.gov (United States)

    Sahu, Maitrayee; Sahu, Abhiram

    2015-11-01

    Leptin signaling in the hypothalamus is critical for normal food intake and body weight regulation. Cumulative evidence suggests that besides the signal transducer and activator of transcription-3 (STAT3) pathway, several non-STAT3 pathways including the phosphodiesterase-3B (PDE3B) pathway mediate leptin signaling in the hypothalamus. We have shown that PDE3B is localized in various hypothalamic sites implicated in the regulation of energy homeostasis and that the anorectic and body weight reducing effects of leptin are mediated by the activation of PDE3B. It is still unknown if PDE3B is expressed in the long form of the leptin-receptor (ObRb)-expressing neurons in the hypothalamus and whether leptin induces STAT3 activation in PDE3B-expressing neurons. In this study, we examined co-localization of PDE3B with ObRb neurons in various hypothalamic nuclei in ObRb-GFP mice that were treated with leptin (5mg/kg, ip) for 2h. Results showed that most of the ObRb neurons in the arcuate nucleus (ARC, 93%), ventromedial nucleus (VMN, 94%), dorsomedial nucleus (DMN, 95%), ventral premammillary nucleus (PMv, 97%) and lateral hypothalamus (LH, 97%) co-expressed PDE3B. We next examined co-localization of p-STAT3 and PDE3B in the hypothalamus in C57BL6 mice that were treated with leptin (5mg/kg, ip) for 1h. The results showed that almost all p-STAT3 positive neurons in different hypothalamic nuclei including ARC, VMN, DMN, LH and PMv areas expressed PDE3B. These results suggest the possibility for a direct role for the PDE3B pathway in mediating leptin action in the hypothalamus. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. ¿La Apoteosis de Heracles o una escena de Apobates? A propósito de una cratera de campana procedente de La Loma del Escorial de Los Nietos (Cartagena, Murcia

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    Rodríguez Pérez, Diana

    2014-12-01

    Full Text Available The aim of this article is to assess the traditional iconographic identification of the obverse of a 4th century Greek bell crater from the Iberian site of La Loma del Escorial de Los Nietos (Cartagena, Murcia. The scene has been identified as an apotheosis of Heracles. Nevertheless, a detailed analysis of its iconography and of a feature neglected in the previous study of the vase by its excavators —the remains of a shield— make it possible to argue in favor of an apobates race instead —the only scene of this type attested in the Iberian Peninsula. I present here an analysis of both iconographic motifs —the apotheosis of Heracles and the apobates race— that will reveal interesting findings on the ways in which images and iconographic types acquire meaning. It also sheds light on the kind of images favored by the receptors of these vases in the Peninsula — the Iberians. An up-to-date catalogue of Attic vases depicting each theme is included.En el presente artículo se revisa la identificación iconográ- fica de la cara A de una cratera griega fragmentaria del siglo IV a.C. procedente del yacimiento ibérico de La Loma del Escorial de Los Nietos (Cartagena, Murcia. La escena se ha identificado tradicionalmente como la apoteosis de Heracles, no obstante, tras un análisis detallado de la misma, en particular del resto de un escudo previamente inadvertido que porta el personaje principal, creemos que la iconografía se corresponde con la del apobates victorioso, un unicum en la Península Ibérica. Presentamos un análisis de ambos motivos iconográficos que revelará interesantes conclusiones sobre el funcionamiento de los tipos iconográficos y mecanismos de creación de significado en la pintura de vasos de la época, así como sobre el tipo de imágenes estimadas por los receptores de esas piezas en la Península Ibérica, los íberos. Se incluye también un catálogo actualizado de los vasos áticos que portan ambos temas.

  18. Central injection of a synthetic chicken partial leptin peptide does not affect food intake in chicks.

    Science.gov (United States)

    Sims, Wil; Yi, Jiaqing; Cline, Mark A; Gilbert, Elizabeth R

    2017-08-24

    Leptin is an adipose tissue-derived hormone in mammals that plays an important role in whole body energy balance via its inhibitory effects on food intake mediated through the hypothalamus. Chicken leptin has a low sequence homology to mammalian leptin and its role in appetite regulation is not reported; hence the objective of this study was to determine effects of central injection of chicken leptin on food and water intake and associated behaviors in chicks. Chicks were intracerebroventricularly injected with 0 (vehicle), 0.3, 1.0, or 3.0 nmol of a synthetic chicken leptin partial peptide and food and water intake were monitored. There were no effects observed and a second experiment was conducted to evaluate food and water intake at higher doses; after injection of 0, 2.5, 5.0, or 10.0 nmol leptin. Again, there were no effects on food or water intake. In the third experiment, behaviors were analyzed during the first 30 min post-injection of vehicle or 10 nmol leptin. At 5 min post-injection, vehicle-injected chicks spent more time sitting than leptin-injected chicks. A wide dose range was evaluated however, the absence of an effect on food intake or behavior suggests that the chicken leptin peptide that was tested does not mediate effects on appetite in the brain and that chicken leptin likely has a different physiological role in birds than in mammals. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Leptin in the hindbrain facilitates phosphorylation of STAT3 in the hypothalamus.

    Science.gov (United States)

    Desai, Bhavna N; Harris, Ruth B S

    2015-03-01

    Leptin receptors (ObRs) in the forebrain and hindbrain have been independently recognized as important mediators of leptin responses. We recently used low-dose leptin infusions to show that chronic activation of both hypothalamic and hindbrain ObRs is required to reduce body fat. The objective of the present study was to identify the brain nuclei that are selectively activated in rats that received chronic infusion of leptin in both the forebrain and hindbrain. Either saline or leptin was infused into third and fourth ventricles (0.1 μg/24 h in the third ventricle and 0.6 μg/24 h in the fourth ventricle) of male Sprague-Dawley rats for 6 days using Alzet pumps. Rats infused with leptin into both ventricles (LL rats) showed a significant increase in phosphorylated (p)STAT3 immunoreactivity in the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and posterior hypothalamus compared with other groups. No differences in pSTAT3 immunoreactivity were observed in midbrain or hindbrain nuclei despite a sixfold higher infusion of leptin into the fourth ventricle than the third ventricle. ΔFosB immunoreactivity, a marker of chronic neuronal activation, showed that multiple brain nuclei were chronically activated due to the process of infusion, but only the arcuate nucleus, ventromedial hypothalamus, dorsomedial hypothalamus, and ventral tuberomamillary nucleus showed a significant increase in LL rats compared with other groups. These data demonstrate that low-dose leptin in the hindbrain increases pSTAT3 in areas of the hypothalamus known to respond to leptin, supporting the hypothesis that leptin-induced weight loss requires an integrated response from both the hindbrain and forebrain. Copyright © 2015 the American Physiological Society.

  20. Serum leptin and its relationship with metabolic variables in Arabs with type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Al-Shoumer, Kamal A.; Doi, Suhail A.; Vasanthy, Bagavathy A.; Al-Asousi, Adnan A.

    2008-01-01

    Most studies on serum leptin in type 2 diabetes mellitus have focused on white populations. We studied serum leptin concentrations and parameters related to glycemic control and the association between leptin levels and anthropometric and metabolic factors in Arab patients with type 2 diabetes and in Arab control subjects. Ninety-two patients (65 females and 27 males) with type 2 diabetes and 69 matched normal and control subjects (48 females and 21 males) were included. Anthropometric measures (including body mass index (BMI) and waist: hip ratio) were assessed in all subjects. After an overnight fast, blood was collected for serum leptin assay. Other metabolic parameters include glucose, insulin, C-peptide, intact proinsulin, insulin resistance index (HOMA-IR), insulin-like growth factor 1 (IGF-1), lipids and hemoglobin A 1c (HbA) were determined. Fasting serum leptin levels, IGF-1 and high-density lipoprotein (HDL) cholesterol were similar in patients with type 2 diabetes and control subjects. When obese subjects (BMI>-30kg/m2) were analyzed separately, serum levels of leptin were significantly lower in patients compared to controls. In contrast, patients had higher fasting glucose, insulin, C-peptide, intact proinsulin, insulin resistance, total cholesterol, triglycerides, HbA, and a larger waist circumference and waist-to-hip ratio than controls. Serum leptin correlated positively with BM, negatively with waist-to-hip ratio, and demonstrated no relationship to other parameters. Patients with type 2 diabetes in an Arab ethnic population showed evidence of an unfavorable metabolic profile despite having leptin levels similar to controls. Obesity influences serum leptin levels more significantly in type 2 diabetes, in which leptin levels tends to be low. (author)

  1. Bone mass acquisition in female rhythmic gymnasts during puberty: no direct role for leptin.

    Science.gov (United States)

    Maïmoun, Laurent; Coste, Olivier; Jaussent, Audrey; Mariano-Goulart, Denis; Sultan, Charles; Paris, Françoise

    2010-05-01

    Although hypoleptinaemia has been reported in female peripubertal athletes, data are lacking on leptin and bone mass variations in puberty and the effects of leptin on bone mineralization during this period. This study therefore investigated the variations in leptin level and bone mineral density (BMD) in young elite female rhythmic gymnasts (FRG) according to pubertal stage. The effects of leptin, IGF-1 and sex hormones on bone mineral acquisition were also evaluated. Plasma leptin levels were analysed in 43 elite FRG (mean age: 13.3 +/- 1.8 years range: 10.6-17.2, body mass index: 17.52 +/- 1.85 kg/m(2), training status: 17.9-23.8 h/week) according to their pubertal stage (Tanner I, n = 7; II, n = 10; III, n = 9; IV, n = 8; V, n = 9). IGF-1, IGFBP-3 and sex hormones were also evaluated. BMD was measured by dual-energy X-ray absorptiometry at various bone sites. Plasma leptin increased throughout pubertal growth and the values measured in Tanner stages IV-V were significantly higher than in stages I-II. Gains in BMD were measured throughout puberty at all bone sites, particularly between Tanner stages II and IV. In simple correlation analysis, BMD at all bone sites was positively correlated with plasma leptin, age, bone age, BMI, oestrogen, testosterone, IGF-1 and IGFBP-3. However, multivariate analysis using a linear regression model by block (including bone age, anthropometric data and biological parameters) was then performed to determine the factors independently associated with each BMD site, and only bone age, fat-free soft tissue and BMI remained independent predictors. In FRG characterized by high training volume and low fat mass, plasma leptin levels increased throughout puberty and were partially related to body composition changes. Despite the simultaneous increases in plasma leptin and BMD during pubertal growth, it was not possible to differentiate the leptin impact on bone independently from anthropometric parameters.

  2. Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

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    E. Erhardt

    2006-12-01

    Full Text Available The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 µg/kg or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina but receiving recombinant leptin (rLeptin or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68 = 7.834, P = 0.007. There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34 = 3.751, P = 0.020 and exploration (F(3,34 = 3.581, P = 0.024. These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

  3. Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis

    International Nuclear Information System (INIS)

    Fiorio, Elena; Bonetti, Franco; Giordano, Antonio; Cetto, Gian Luigi; Surmacz, Eva; Mercanti, Anna; Terrasi, Marianna; Micciolo, Rocco; Remo, Andrea; Auriemma, Alessandra; Molino, Annamaria; Parolin, Veronica; Di Stefano, Bruno

    2008-01-01

    Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Expression of ObR, HER2, phospo-HER2 was assessed by immonoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments

  4. An assessment of serum leptin levels in patients with chronic viral hepatitis: a prospective study

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    Katsanika Aggeliki

    2007-05-01

    Full Text Available Abstract Background The role of leptin in the course of liver disease due to chronic viral hepatitis (CVH remains controversial. Our aims were to investigate the relationship between serum leptin concentrations and the severity of liver disease in a cohort of subjects with HBeAg negative chronic hepatitis B (CHB and C (CHC and to analyze the effect of body composition, the leptin system and insulin resistance together with viral factors on virologic response to antiviral treatment. Methods We studied 50 (36 men consecutive patients suffering from biopsy-proven CVH due to HBV (n = 25 or HCV (n = 25 infection. Thirty-two (17 men healthy volunteers served as controls. Levels of serum leptin and insulin were determined by immunoassays at baseline and at the end of the treatment. Results A significant association between serum leptin levels and the stage of hepatic fibrosis was noted; patients with cirrhosis presented higher serum leptin levels compared to those with lower fibrosis stage [CHB patients (17436 pg/ml vs 6028.5 pg/ml, p = 0.03, CHC patients (18014 pg/ml vs 4385 pg/ml, p = 0.05]. An inverse correlation between lower leptin levels and response to lamivudine monotherapy was noted in patients with CHB; those with a virologic response presented lower serum leptin levels (5334 vs 13111.5 pg/ml; p-value = 0.003 than non-responders. In genotype 1 CHC patients, insulin resistance played a significant role in the response to antiviral therapy. Conclusion Our data clearly suggest that cirrhosis due to CHB or CHC is associated with higher leptin levels. Increased serum leptin levels represent a negative prognostic factor for response to lamivudine monotherapy in patients with CHB. In CHC patients insulin resistance strongly influences the response to antiviral treatment in patients infected with genotype 1.

  5. Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

    Science.gov (United States)

    Hoang, Don; Broer, Niclas; Sosa, Julie A; Abitbol, Nathalie; Yao, Xiaopan; Li, Fangyong; Rivera-Molina, Felix; Toomre, Derek K; Roman, Sanziana A; Sue, Gloria; Kim, Samuel; Li, Alexander Y; Callender, Glenda G; Simpson, Christine; Narayan, Deepak

    2017-12-01

    We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

  6. Endogenous leptin contributes to baroreflex suppression within the solitary tract nucleus of aged rats.

    Science.gov (United States)

    Arnold, Amy C; Diz, Debra I

    2014-12-01

    The decline in cardiovagal baroreflex function that occurs with aging is accompanied by an increase in circulating leptin levels. Our previous studies showed that exogenous leptin impairs the baroreflex sensitivity for control of heart rate in younger rats, but the contribution of this hormone to baroreflex dysfunction during aging is unknown. Thus we assessed the effect of bilateral leptin microinjection (500 fmol/60 nl) within the solitary tract nucleus (NTS) on the baroreflex sensitivity in older (66 ± 2 wk of age) urethane/chloralose anesthetized Sprague-Dawley rats with elevated circulating leptin levels. In contrast to the 63% reduction observed in younger rats, leptin did not alter the baroreflex sensitivity for bradycardia evoked by phenylephrine in older rats (0.76 ± 0.19 baseline vs. 0.71 ± 0.15 ms/mmHg after leptin; P = 0.806). We hypothesized that this loss of sensitivity reflected endogenous suppression of the baroreflex by elevated leptin, rather than cardiovascular resistance to the peptide. Indeed, NTS administration of a leptin receptor antagonist (75 pmol/120 nl) improved the baroreflex sensitivity for bradycardia in older rats (0.73 ± 0.13 baseline vs. 1.19 ± 0.26 at 10 min vs. 1.87 ± 0.32 at 60 min vs. 1.22 ± 0.54 ms/mmHg at 120 min; P = 0.002), with no effect in younger rats. There was no effect of the leptin antagonist on the baroreflex sensitivity for tachycardia, responses to cardiac vagal chemosensitive fiber activation, or resting hemodynamics in older rats. These findings suggest that the actions of endogenous leptin within the NTS, either produced locally or derived from the circulation, contribute to baroreflex suppression during aging. Copyright © 2014 the American Physiological Society.

  7. Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

    Science.gov (United States)

    Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2012-05-15

    The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body

  8. Liraglutide, leptin and their combined effects on feeding: additive intake reduction through common intracellular signalling mechanisms.

    Science.gov (United States)

    Kanoski, S E; Ong, Z Y; Fortin, S M; Schlessinger, E S; Grill, H J

    2015-03-01

    To investigate the behavioural and intracellular mechanisms by which the glucagon like peptide-1 (GLP-1) receptor agonist, liraglutide, and leptin in combination enhance the food intake inhibitory and weight loss effects of either treatment alone. We examined the effects of liraglutide (a long-acting GLP-1 analogue) and leptin co-treatment, delivered in low or moderate doses subcutaneously (s.c.) or to the third ventricle, respectively, on cumulative intake, meal patterns and hypothalamic expression of intracellular signalling proteins [phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein tyrosine phosphatase-1B (PTP1B)] in lean rats. A low-dose combination of liraglutide (25 µg/kg) and leptin (0.75 µg) additively reduced cumulative food intake and body weight, a result mediated predominantly through a significant reduction in meal frequency that was not present with either drug alone. Liraglutide treatment alone also reduced meal size; an effect not enhanced with leptin co-administration. Moderate doses of liraglutide (75 µg/kg) and leptin (4 µg), examined separately, each reduced meal frequency, cumulative food intake and body weight; only liraglutide reduced meal size. In combination these doses did not further enhance the anorexigenic effects of either treatment alone. Ex vivo immunoblot analysis showed elevated pSTAT3 in the hypothalamic tissue after liraglutide-leptin co-treatment, an effect which was greater than that of leptin treatment alone. In addition, s.c. liraglutide reduced the expression of PTP1B (a negative regulator of leptin receptor signalling), revealing a potential mechanism for the enhanced pSTAT3 response after liraglutide-leptin co-administration. Collectively, these results show novel behavioural and molecular mechanisms underlying the additive reduction in food intake and body weight after liraglutide-leptin combination treatment. © 2014 John Wiley & Sons Ltd.

  9. Association of single nucleotide polymorphisms in the bovine leptin and leptin receptor genes with growth and ultrasound carcass traits in Nellore cattle.

    Science.gov (United States)

    da Silva, R C G; Ferraz, J B S; Meirelles, F V; Eler, J P; Balieiro, J C C; Cucco, D C; Mattos, E C; Rezende, F M; Silva, S L

    2012-10-11

    Given the important role of leptin in metabolism, we looked for a possible association of leptin and leptin receptor polymorphisms with carcass and growth traits in Nellore cattle. We examined associations of leptin and leptin receptor SNPs with ultrasound carcass (longissimus dorsi muscle area (ribeye area), backfat thickness and rump fat thickness and growth traits (weaning weight adjusted to 210 days of age, yearling weight adjusted to 550 days of age, weight gain of weaning to yearling and scrotal circumference adjusted to 550 days of age) of 2162 Bos primigenius indicus (Nellore) animals. Allele and genotypic frequencies were calculated for each marker. Allele substitution, additive and dominance effects of the polymorphisms were also evaluated. Some alleles of the molecular markers had low frequencies, lower than 1%, in the sample analyzed, although the same polymorphisms described for B. p. taurus cattle were found. Due to very low allelic frequencies, the E2JW, A59V and UASMS2 markers were not included in the analysis, because they were almost fixed. E2FB was found to be significantly associated with weight gain, ribeye area and backfat thickness. The promoter region markers, C963T and UASMS1, were also found to be significantly associated with ribeye area. T945M was significantly associated with weight gain. We conclude that the leptin and receptor gene markers would be useful for marker-assisted selection.

  10. Serum Concentration of Leptin in Pregnant Adolescents Correlated with Gestational Weight Gain, Postpartum Weight Retention and Newborn Weight/Length

    Science.gov (United States)

    Sámano, Reyna; Martínez-Rojano, Hugo; Godínez-Martínez, Estela; Sánchez-Jiménez, Bernarda; Montiel-Ojeda, Diana; Tolentino, Maricruz

    2017-01-01

    Introduction: Gestational weight gain is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Leptin is normally correlated with adiposity and is also known to increase throughout pregnancy, as the placenta becomes a source of leptin synthesis. Several studies have reported positive correlations between cord blood leptin level and either birthweight or size for gestational age, as well as body mass index (BMI). Objective: To determine the correlation of prenatal leptin concentration in pregnant adolescents with their gestational weight gain, postpartum weight retention, and weight/length of their newborn. Methods: A cohort study was conducted on pregnant Mexican adolescents from Gestational Week 26–28 to three months postpartum (n = 168 mother–child dyads). An anthropometric assessment was made of each pregnant adolescent, and the serum level of leptin and the intake of energy were determined. The newborn was evaluated each month during postpartum. Clinical records were reviewed to obtain sociodemographic data. Bivariate correlations, tests for repeating measurements and logistic regression models were performed. Results: Leptin concentration gradually increased during the third trimester of pregnancy. At Gestation Week 36, leptin level correlated with gestational weight gain. When comparing adolescents that had the lowest and highest concentration of leptin, the former presented a mean of 6 kg less in gestational weight gain (inter-subject leptin concentration, p = 0.001; inter-subject energy intake, p = 0.497). Leptin concentration and gestational weight gain exerted an effect on the weight of the newborn (inter-subject leptin concentration for Week 32, p = 0.024; inter-subject gestational weight gain, p = 0.011). Newborn length was associated with leptin concentration at Week 28 (leptin effect, p = 0.003; effect of gestational weight gain, p = 0.722). Conclusions: Pregnant adolescents with leptin

  11. Serum Leptin Measured in Early Pregnancy Is Higher in Women With Preeclampsia Compared With Normotensive Pregnant Women

    DEFF Research Database (Denmark)

    Taylor, Brandie; Ness, Roberta B; Olsen, Jørn

    2015-01-01

    Leptin, an adipocyte-derived hormone, plays an important role in reproduction and angiogenesis. Studies examining leptin in preeclampsia are inconsistent, possibly because of small sample sizes and variability in sampling and outcome. We conducted a nested case-control study to examine associations...... between serum leptin (measured: 9-26 weeks gestation) and preeclampsia among 430 primiparous preeclamptic women and 316 primiparous normotensive controls from the Danish National Birth Cohort. Median (interquartile range) leptin concentrations were calculated. Associations between leptin and preeclampsia...... (blood pressure ≥140/90 mm Hg), term preeclampsia (preeclampsia and delivery ≥37 weeks gestation), or preterm preeclampsia (preeclampsia and delivery

  12. Dietary intake and ghrelin and leptin changes after sleeve gastrectomy.

    Science.gov (United States)

    Bužga, Marek; Zavadilová, Vladislava; Holéczy, Pavol; Švagera, Zdeněk; Švorc, Pavol; Foltys, Aleš; Zonča, Pavel

    2014-12-01

    Surgical intervention in obesity is today the most effective treatment method in high level obesity management. Bariatric interventions not only ensure body weight reduction, but may influence dietary habits. To assess changes in adipose hormones and dietary habits in obese patients after sleeve gastrectomy. The study set comprised 37 subjects (29 females and 8 males) 24 to 68 years old with body mass index 43.0 ±4.9 kg/m(2). Pre-operative examination included baseline measurements of body composition. Dietary habits and intake frequency were monitored by a questionnaire method. Follow-up examinations were carried out in a scope identical to the pre-operative examination, 6 and 12 months after surgery, respectively. The average patient weight loss 12 months after surgery was 31.7 kg. Excess weight loss was 55.2 ±20.6%. Patients reported reduced appetite (p meal portions per day (p = 0.003) and a decrease in consuming the largest portions during the afternoon and evening (p = 0.030). Plasma levels of fasting glucose, leptin and ghrelin significantly decreased (p = 0.006; p = 0.0.043); in contrast, the level of adiponectin significantly increased (p weight reduction within 1 year after surgery. An improvement of certain dietary habits in patients was registered. At 12 months after surgery, there were no statistically significant differences in decreases in ghrelin and leptin concentrations between patients without changed appetite and those reporting decreased appetite.

  13. Obesity, diabetes and leptin: lessons learned from obese hyperglycemic mice

    Directory of Open Access Journals (Sweden)

    Meftun Ahmed

    2008-07-01

    Full Text Available The recent epidemic nature of obesity and association of obesity with the development of type 2 diabetes demands dissection of the pathophysiology of this morbid disorder which is essential for better understanding of the process of evolution of insulin resistance. Different animal models have been used to explore the mechanism linking obesity to insulin resistance and type 2 diabetes. The discovery of ob gene and its product, leptin, has revealed the signaling system regulating energy balance in rodents. The mice lacking this ob gene, ob/ob mice, display obesity, hyperglycemia and hyperinsulinemia and has been extensively used for the study of type 2 diabetes and for potential drug development. In this review, the features and development of obese hyperglycemic syndrome, the role of leptin in the pathogenesis of the syndrome and finally the applicability of the findings in rodents to body weight regulation and pathogenesis of insulin resistance in humans have been summarized. Ibrahim Med. Coll. J. 2008; 2(2: 72-84

  14. Differential Effects of Leptin and Adiponectin in Endothelial Angiogenesis

    Directory of Open Access Journals (Sweden)

    Raghu Adya

    2015-01-01

    Full Text Available Obesity is a major health burden with an increased risk of cardiovascular morbidity and mortality. Endothelial dysfunction is pivotal to the development of cardiovascular disease (CVD. In relation to this, adipose tissue secreted factors termed “adipokines” have been reported to modulate endothelial dysfunction. In this review, we focus on two of the most abundant circulating adipokines, that is, leptin and adiponectin, in the development of endothelial dysfunction. Leptin has been documented to influence a multitude of organ systems, that is, central nervous system (appetite regulation, satiety factor and cardiovascular system (endothelial dysfunction leading to atherosclerosis. Adiponectin, circulating at a much higher concentration, exists in different molecular weight forms, essentially made up of the collagenous fraction and a globular domain, the latter being investigated minimally for its involvement in proinflammatory processes including activation of NF-κβ and endothelial adhesion molecules. The opposing actions of the two forms of adiponectin in endothelial cells have been recently demonstrated. Additionally, a local and systemic change to multimeric forms of adiponectin has gained importance. Thus detailed investigations on the potential interplay between these adipokines would likely result in better understanding of the missing links connecting CVD, adipokines, and obesity.

  15. Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice.

    Science.gov (United States)

    Niki, Mayu; Jyotaki, Masafumi; Yoshida, Ryusuke; Yasumatsu, Keiko; Shigemura, Noriatsu; DiPatrizio, Nicholas V; Piomelli, Daniele; Ninomiya, Yuzo

    2015-06-01

    Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor deficient (db/db) and diet-induced obese (DIO) mice. Chorda tympani (CT) nerve responses of lean mice to sweet compounds were increased after administration of leptin antagonist (LA) but not affected by administration of cannabinoid receptor antagonist (AM251). db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid levels in the taste organ, and enhanced expression of a biosynthesizing enzyme of endocannabinoids in taste cells. The effect of LA was gradually decreased and that of AM251 was increased during the course of obesity in DIO mice. These findings suggest that circulating leptin, but not local endocannabinoids, is a dominant modulator for sweet taste in lean mice and endocannabinoids become more effective modulators of sweet taste under conditions of deficient leptin signalling. Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob-Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob-Rb: L39A/D40A/F41A (LA), CB1 : AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet-induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA

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

    Science.gov (United States)

    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

  17. 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.

    Science.gov (United States)

    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

  18. Daily rhythms of plasma melatonin, but not plasma leptin or leptin mRNA, vary between lean, obese and type 2 diabetic men.

    Directory of Open Access Journals (Sweden)

    Simone Mäntele

    Full Text Available Melatonin and leptin exhibit daily rhythms that may contribute towards changes in metabolic physiology. It remains unclear, however, whether this rhythmicity is altered in obesity or type 2 diabetes (T2DM. We tested the hypothesis that 24-hour profiles of melatonin, leptin and leptin mRNA are altered by metabolic status in laboratory conditions. Men between 45-65 years old were recruited into lean, obese-non-diabetic or obese-T2DM groups. Volunteers followed strict sleep-wake and dietary regimes for 1 week before the laboratory study. They were then maintained in controlled light-dark conditions, semi-recumbent posture and fed hourly iso-energetic drinks during wake periods. Hourly blood samples were collected for hormone analysis. Subcutaneous adipose biopsies were collected 6-hourly for gene expression analysis. Although there was no effect of subject group on the timing of dim light melatonin onset (DLMO, nocturnal plasma melatonin concentration was significantly higher in obese-non-diabetic subjects compared to weight-matched T2DM subjects (p<0.01 and lean controls (p<0.05. Two T2DM subjects failed to produce any detectable melatonin, although did exhibit plasma cortisol rhythms comparable to others in the group. Consistent with the literature, there was a significant (p<0.001 effect of subject group on absolute plasma leptin concentration and, when expressed relative to an individual's 24-hour mean, plasma leptin showed significant (p<0.001 diurnal variation. However, there was no difference in amplitude or timing of leptin rhythms between experimental groups. There was also no significant effect of time on leptin mRNA expression. Despite an overall effect (p<0.05 of experimental group, post-hoc analysis revealed no significant pair-wise effects of group on leptin mRNA expression. Altered plasma melatonin rhythms in weight-matched T2DM and non-diabetic individuals supports a possible role of melatonin in T2DM aetiology. However, neither

  19. Leptin but not ciliary neurotrophic factor (CNTF) induces phosphotyrosine phosphatase-1B expression in human neuronal cells (SH-SY5Y): putative explanation of CNTF efficacy in leptin-resistant state.

    Science.gov (United States)

    Benomar, Yacir; Berthou, Flavien; Vacher, Claire-Marie; Bailleux, Virginie; Gertler, Arieh; Djiane, Jean; Taouis, Mohammed

    2009-03-01

    Growing evidences suggest that obesity is associated with hypothalamic leptin resistance, leading to the alteration of food intake control. Alternative treatment using ciliary neurotrophic factor (CNTF) has been suggested because CNTF exerts a leptin-like effect, even in leptin-resistant states, but the mechanisms by which CNTF maintains this effect are not yet understood. Both leptin and CNTF act in the hypothalamus through similar signaling pathways including janus kinase-2/signal transducer and activator of transcription (STAT)-3 pathway. To explore the differences and interactions between leptin and CNTF signaling pathways, differentiated human neuroblastoma cells (SH-SY5Y) were exposed to either leptin or CNTF and then challenged for each cytokine. Leptin pretreatment completely abolished leptin-dependent STAT-3 and ERK 1/2 phosphorylations without affecting CNTF action. The lack of cross-desensitization between leptin and CNTF signaling pathways occurred despite the induction of suppressor of cytokine signaling-3 in response to both cytokines. Interestingly, leptin as well as insulin induced the expression of phosphotyrosine phosphatase (PTP)-1B, whereas CNTF treatment did not affect its expression. In addition, acute leptin treatment but not CNTF induced PTP-1B expression in mouse hypothalamic arcuate nucleus. Furthermore, the overexpression of human PTP-1B in SH-SY5Y cells completely abolished leptin- and insulin-dependent janus kinase-2, STAT-3, and ERK 1/2 phosphorylations, but CNTF action was not altered. Collectively, our results suggest that PTP-1B constitutes a key divergent element between leptin/insulin and CNTF signaling pathways at the neuronal level, which may constitute a possible mechanism that explains the efficacy of CNTF in leptin-resistant states.

  20. Leptin levels and luteinizing hormone pulsatility in normal cycling women and their relationship to daily changes in metabolic rate.

    Science.gov (United States)

    Fenichel, Rebecca M; Dominguez, Jennifer E; Mayer, Laurel; Walsh, B Timothy; Boozer, Carol; Warren, Michelle P

    2008-10-01

    To determine whether leptin and LH secretion in normal women is related to changes in metabolic rate. Academic medical center. PATIENT(S) AND DESIGN: Ten young women with normal weight and menses were studied during the early follicular phase. Leptin and LH levels were sampled every 15 minutes over a 24-hour period. Metabolic rate was frequently sampled using indirect calorimetry. Luteinizing hormone pulsatility was analyzed using a Cluster Program analysis. None. Leptin, LH, and metabolic rate levels. All subjects demonstrated a diurnal leptin curve. Luteinizing hormone pulses were increased in amplitude and slower after the leptin peak. The average (+/-SE) number of LH pulses per 6 hours slowed from 4.30 +/- 0.42 to 3.00 +/- 0.42 pulses after the leptin peak, whereas pulse amplitude increased from 1.64 +/- 0.26 to 2.51 +/- 0.42 mIU/mL after the leptin peak. The LH interpulse interval increased from 85.1 +/- 3.64 minutes to 108.8 +/- 10.26 minutes after the leptin peak. Metabolic rate began to drop approximately 4-6 hours before leptin levels peaked, going from 1.66 +/- 0.24 to 1.15 +/- 0.04 kcal/min after the leptin peak. There is a significant association between the timing of the leptin peak, the nightly slowing of LH pulses, and the fall in metabolic rate, suggesting a metabolic cycle in normal individuals.

  1. Studies on the relationship between leptin secretion and several pregnancy-related hormones during pregnancy in the golden hamster

    International Nuclear Information System (INIS)

    Wang Chen; Yang Liguo; Gen Watanabe; Kazuyoshi Taya

    2003-01-01

    Objective: To determine the relationships between leptin secretion and several pregnancy related hormones, the body weight as well as food intaken in the golden hamster during pregnancy and early lactation. Methods: 100 golden hamsters were mated and divided into 16 groups. Blood specimens were taken at 11:00 daily and were determined for plasma leptin, growth hormone (GH), follicular stimulating hormone (FSH), luteinizing hormone (LH), progesterone estradiol and inhibin with RIA. Relationships between leptin level and food intake as well as material body weight were also noted. Results: A plasma leptin peak level occurred on day 12 of the pregnancy. Leptin levels were significantly correlated with levels of gonadal hormones but not with pituitary hormones. Food intake and material total body weight (including the fetus) bore no significant correlationship with plasma leptin throughout the whole pregnancy stage. However, if the fetus weight was subtracted, the net maternal body weight would be significantly correlated with the leptin concentration. Conclusion: These results suggest that leptin-resistance may exits in the golden hamster during pregnancy. Some pregnancy-related hormones, especially gonadal hormones, have regulatory effect on the secretion of leptin. Positive correlation between leptin and net maternal body weight suggests that leptin is still a signal of the body weight to the central nerves system during pregnancy

  2. The correlation between serum leptin and blood pressure after exposure to noise at work

    Directory of Open Access Journals (Sweden)

    Muayad S Rahma

    2013-01-01

    Full Text Available Several epidemiologic studies have reported that exposure to noise is associated with cardiovascular disease. The increased body weight is often associated with metabolic as well as increased blood pressure. The aim of this study is to investigate the correlation between the elevation of blood pressure and serum leptin hormones due to the effects of noise in the work place. A total of 80 volunteer males where included in this study with an age range between of 20 and 45 years, they were divided in two groups equally, the 1 st group were exposed to noise in the workplace while the 2 nd group were not. The individual noise exposure was determined by using a sound level meter. The range of noise was 80-100 dBA. Body Mass Index was also taken for each individual by a standard measure, blood pressure was measured by OMRON sphygmomanometer and serum leptin was measured through venous blood sample analysis enzyme linked immunosorbent assay. Spearman rank order correlation was used to examine the correlations between Blood pressure value (Systolic, Diastolic and Leptin. All the relationships between parameters showed a positive correlation. Systolic and diastolic blood pressure values had a significant correlation to leptin hormone level in comparison to the control. There was a significant relation between leptin and blood pressure. leptin effects on the sympathetic nervous system may provide a partial explanation. Therefore, Leptin might have diverse cardiovascular actions.

  3. The role of leptin as a biomarker in the relationship between periodontitis and chronic migraine.

    Science.gov (United States)

    Leira, Yago; Ameijeira, Pablo; Domínguez, Clara; Leira, Rogelio; Blanco, Juan

    2017-12-01

    To evaluate the prevalence of periodontitis (CP) and its contribution to serum leptin levels in chronic migraine (CM). In this case-control study, we included 150 subjects divided into healthy controls (n = 58) and CM patients (n = 92). Demographic, neurological, clinical data as well as full-mouth periodontal records were obtained. Serum leptin levels were measured by ELISA technique. Both the prevalence of CP and mean serum leptin levels were significantly higher in patients with CM in comparison with controls (57.6% versus 36.2%, p = .01 and 16.4 versus 7.2 ng/ml, p < .0001, respectively). Patients from the CM group who had CP showed significantly higher leptin concentrations than CM patients without CP (19.8 versus 11.8 ng/ml, p < .0001). Multivariable linear regression analysis showed that CP was an independent contributor to raised leptin levels in CM patients (R 2  = 0.270, p = 0.013). CP is prevalent in CM patients and when present it contributes to elevated serum leptin levels, independently of other confounding factors. Therefore, it seems that CP via leptin could be involved in the process of migraine chronification. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. The role of adiposity in the relationship between serum leptin and severe major depressive episode.

    Science.gov (United States)

    Ubani, Chinedu C; Zhang, Jian

    2015-08-30

    To assess the role that adiposity plays in the association between leptin and major depressive episode (MDE), we analyzed the data of 1046 men and 1359 women aged 20-39 years, who completed an interview and had blood collected as a part of the National Health and Nutrition Examination Survey (NHANES) between 1991 and 1994. Waist-hip ratio (WHR) was used as an indicator of adiposity. MDE was assessed with the Diagnostic Interview Schedule. For normal-WHR women, the prevalence of MDE was reversely associated with leptin levels, 13.7(4.4)%, 12.2(4.0)% and 2.3(1.8)% respectively for lower, interquartile, and upper quartile. For abnormal-WHR women, the prevalence of MDE was positively associated with leptin, 6.1(2.3)%, 9.1(2.4)% and 20.0 (3.8) respectively for the three leptin levels. Compared to women with lower quartile of leptin, the odds ratio of MDE for women with upper quartile was 0.09 (0.01-0.98) for normal-WHR women but 4.35 (1.55-12.2) for abnormal-WHR women. No moderating effects were observed among men. Using BMI in place of WHR revealed similar findings. The association between MDE and leptin is moderated by adiposity. High leptin levels are associated with low odds of MDE among women with normal adiposity but high odds among women with abnormal adiposity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Teasaponin improves leptin sensitivity in the prefrontal cortex of obese mice.

    Science.gov (United States)

    Yu, Yinghua; Wu, Yizhen; Szabo, Alexander; Wang, Sen; Yu, Shijia; Wang, Qing; Huang, Xu-Feng

    2015-12-01

    Obesity impairs cognition, and the leptin-induced increase of brain-derived neurotrophic factor (BDNF) and neurogenesis. Tea consumption improves cognition and increases brain activation in the prefrontal cortex. This study examined whether teasaponin, an active ingredient in tea, could improve memory and central leptin effects on neurogenesis in the prefrontal cortex of obese mice, and in vitro in cultured prefrontal cortical neurons. Teasaponin (10 mg/kg, intraperitoneal) for 21 days improved downstream leptin signaling (JAK2 and STAT3), and leptin's effect on BDNF, in the prefrontal cortex of high-fat diet (HFD) fed mice. Prefrontal cortical neurons were cultured with teasaponin and palmitic acid (the most abundant dietary saturated fatty acid) to examine their effects on neurogenesis and BDNF expression in response to leptin. Palmitic acid decreased leptin's effect on neurite outgrowth, postsynaptic density protein 95, and BDNF expression in cultured cortical neurons, which was reversed by teasaponin. Teasaponin improved the leptin sensitivity of prefrontal cortical neurons in obese mice or when treated by palmitic acid. This in turn increased BDNF expression and neurite growth. Therefore, teasaponin supplementation may be used to prevent obesity-associated neurodegeneration and improve cognitive function. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa.

    Science.gov (United States)

    Exner, C; Hebebrand, J; Remschmidt, H; Wewetzer, C; Ziegler, A; Herpertz, S; Schweiger, U; Blum, W F; Preibisch, G; Heldmaier, G; Klingenspor, M

    2000-09-01

    Semi-starvation induced hyperactivity (SIH) occurs in rodents upon caloric restriction. We hypothesized that SIH is triggered by the decline in leptin secretion associated with food restriction. To test this hypothesis, rats, which had established a stable level of activity, were treated with leptin or vehicle via implanted minipumps concomitantly to initiation of food restriction for 7 days. In a second experiment treatment was initiated after SIH had already set in. In contrast to the vehicle-treated rats, which increased their baseline activity level by 300%, the development of SIH was suppressed by leptin. Furthermore, leptin was able to stop SIH, after it had set in. These results underscore the assumed major role of leptin in the adaptation to semi-starvation. Because SIH has been viewed as a model for anorexia nervosa, we also assessed subjective ratings of motor restlessness in 30 patients with this eating disorder in the emaciated state associated with hypoleptinemia and after increments in leptin secretion brought upon by therapeutically induced weight gain. Hypoleptinemic patients ranked their motor restlessness higher than upon attainment of their maximal leptin level during inpatient treatment. Thus, hypoleptinemia might also contribute to the hyperactivity frequently associated with anorexia nervosa.

  7. Comparative acute effects of leptin and insulin on gluconeogenesis and ketogenesis in perfused rat liver.

    Science.gov (United States)

    Borba-Murad, Glaucia Regina; Mario, Erica Guilhen; Bassoli, Bruna Kempfer; Bazotte, Roberto Barbosa; de Souza, Helenir Medri

    2005-01-01

    The acute effects of physiological levels of leptin (10 ng ml(-1)) and insulin (20 microU ml(-1)) on hepatic gluconeogenesis and ketogenesis were compared. Leptin or insulin alone decreased (p<0.05) the activation of hepatic glucose, L-lactate and urea production from L-alanine. However, the hepatic glucose production was not modified if leptin was combined with insulin. These results indicated that both, i.e. leptin and insulin, could promote a non-additive reduction in the rate of catabolism of L-alanine. However, in contrast with insulin (p<0.05), leptin did not inhibit the activation of hepatic glucose production from pyruvate or glycerol. On the other hand, activation of hepatic production of acetoacetate and beta-hydroxybutyrate from octanoate was not affected by leptin or insulin. Thus, our data demonstrate that the acute effect of leptin on hepatic metabolism was partially similar to insulin (activation of glucose production from L-alanine and activation of acetoacetate or beta-hydroxybutyrate production from octanoate) and partially different from insulin (activation of glucose production from pyruvate or glycerol). Copyright (c) 2004 John Wiley & Sons, Ltd.

  8. Central exercise action increases the AMPK and mTOR response to leptin.

    Directory of Open Access Journals (Sweden)

    Eduardo R Ropelle

    Full Text Available AMP-activated protein kinase (AMPK and mammalian Target of Rapamycin (mTOR are key regulators of cellular energy balance and of the effects of leptin on food intake. Acute exercise is associated with increased sensitivity to the effects of leptin on food intake in an IL-6-dependent manner. To determine whether exercise ameliorates the AMPK and mTOR response to leptin in the hypothalamus in an IL-6-dependent manner, rats performed two 3-h exercise bouts, separated by one 45-min rest period. Intracerebroventricular IL-6 infusion reduced food intake and pretreatment with AMPK activators and mTOR inhibitor prevented IL-6-induced anorexia. Activators of AMPK and fasting increased food intake in control rats to a greater extent than that observed in exercised ones, whereas inhibitor of AMPK had the opposite effect. Furthermore, the reduction of AMPK and ACC phosphorylation and increase in phosphorylation of proteins involved in mTOR signal transduction, observed in the hypothalamus after leptin infusion, were more pronounced in both lean and diet-induced obesity rats after acute exercise. Treatment with leptin reduced food intake in exercised rats that were pretreated with vehicle, although no increase in responsiveness to leptin-induced anorexia after pretreatment with anti-IL6 antibody, AICAR or Rapamycin was detected. Thus, the effects of leptin on the AMPK/mTOR pathway, potentiated by acute exercise, may contribute to appetite suppressive actions in the hypothalamus.

  9. Leptin Downregulates LPS-Induced Lung Injury: Role of Corticosterone and Insulin

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    Maristella A. Landgraf

    2014-03-01

    Full Text Available Background/Aims: We investigated the effects of leptin in the development of lipopolysaccharide (LPS-induced acute lung inflammation (ALI in lean mice. Methods: Mice were administered leptin (1.0µg/g or leptin (1.0µg/g followed by LPS (1.5µg/g intranasally. Additionally, some animals were given LPS (1.5µg/g or saline intranasally alone, as a control. Tissue samples and fluids were collected six hours after instillation. Results: We demonstrated that leptin alone did not induce any injury. Local LPS exposure resulted in significant acute lung inflammation, characterized by a substantial increase in total cells, mainly neutrophils, in bronchoalveolar lavages (BAL. We also observed a significant lymphocyte influx into the lungs associated with enhanced lung expression of chemokines and cytokines (KC, RANTES, TNF-α, IFN-γ, GM-CSF and VEGF. LPS-induced ALI was characterized by the enhanced expression of ICAM-1 and iNOS in the lungs. Mice that received LPS showed an increase in insulin levels. Leptin, when administered prior to LPS instillation, abolished all of these effects. LPS induced an increase in corticosterone levels, and leptin potentiated this event. Conclusion: These data suggest that exogenous leptin may promote protection during sepsis, and downregulation of the insulin levels and upregulation of corticosterone may be important mechanisms in the amelioration of LPS-induced ALI.

  10. The correlation between serum leptin and blood pressure after exposure to noise at work.

    Science.gov (United States)

    Rahma, Muayad S; Mustafa, Bassma Ezzat; Razali, Ailin; Shamsuddin, Niza; Althunibat, Osama Y

    2013-01-01

    Several epidemiologic studies have reported that exposure to noise is associated with cardiovascular disease. The increased body weight is often associated with metabolic as well as increased blood pressure. The aim of this study is to investigate the correlation between the elevation of blood pressure and serum leptin hormones due to the effects of noise in the work place. A total of 80 volunteer males where included in this study with an age range between of 20 and 45 years, they were divided in two groups equally, the 1 st group were exposed to noise in the workplace while the 2 nd group were not. The individual noise exposure was determined by using a sound level meter. The range of noise was 80-100 dBA. Body Mass Index was also taken for each individual by a standard measure, blood pressure was measured by OMRON sphygmomanometer and serum leptin was measured through venous blood sample analysis enzyme linked immunosorbent assay. Spearman rank order correlation was used to examine the correlations between Blood pressure value (Systolic, Diastolic) and Leptin. All the relationships between parameters showed a positive correlation. Systolic and diastolic blood pressure values had a significant correlation to leptin hormone level in comparison to the control. There was a significant relation between leptin and blood pressure. leptin effects on the sympathetic nervous system may provide a partial explanation. Therefore, Leptin might have diverse cardiovascular actions.

  11. A Hypothalamic Leptin-Glutamate Interaction in the Regulation of Sympathetic Nerve Activity

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2017-01-01

    Full Text Available Accumulated evidence indicates that obesity-induced type 2 diabetes (T2D is associated with enhanced sympathetic activation. The present study was conducted to investigate the role for leptin-glutamate signaling within the hypothalamus in regulating sympathetic nerve activity. In anesthetized rats, microinjections of leptin (5 ng ~ 100 ng into the arcuate nucleus (ARCN and paraventricular nucleus (PVN induced increases in renal sympathetic nerve activity (RSNA, blood pressure (BP, and heart rate (HR. Prior microinjections of NMDA receptor antagonist AP5 (16 pmol into the ARCN or PVN reduced leptin-induced increases in RSNA, BP, and HR in both ARCN and PVN. Knockdown of a leptin receptor with siRNA inhibited NMDA-induced increases in RSNA, BP, and HR in the ARCN but not in the PVN. Confocal calcium imaging in the neuronal NG108 and astrocytic C6 cells demonstrated that preincubation with leptin induced an increase in intracellular calcium green fluorescence when the cells were challenged with glutamate. In high-fat diet and low-dose streptozotocin-induced T2D rats, we found that leptin receptor and NMDA NR1 receptor expressions in the ARCN and PVN were significantly increased. In conclusion, these studies provide evidence that within the hypothalamic nuclei, leptin-glutamate signaling regulates the sympathetic activation. This may contribute to the sympathoexcitation commonly observed in obesity-related T2D.

  12. Development of a radioimmunoassay for the measurement of human leptin in serum

    International Nuclear Information System (INIS)

    Lagarde, A. R.; Nagy, K.; Forgach, T.; Janoki, G. A.

    2003-01-01

    Leptin is a 16 kDa polypeptide hormone encoded by the obese gene (ob) and secreted by adipose tissue. This hormone plays a major role in energy homeostasis and regulation of food intake and body weight. It also affects the metabolic, neuroendocrine and reproductive systems. Labelling of recombinant human leptin with 125I was best performed by the Chloramine-T method. New Zealand white rabbits were immunised with recombinant human leptin, cross-reaction of obtained antisera was analyzed with 10 different antigens. The separation of bound and free fractions was performed using the second antibody - PEG method. The obtained tracer had specific activities of 2.8-3.3 kBq/μg and had a stability of 5 weeks. A highly specific polyclonal antibody was obtained without measurable cross-reaction against the analysed antigens. Concentrations of human leptin were measured by a single overnight incubation assay with a sensitivity of 0.5 ng/ml and a measuring range of 0.5-100 ng/ml. The intra-assay and inter-assay coefficient of variation was under 6% and 8%, respectively. Recovery ranged from 88% to 106%. Serum human leptin concentrations can be accurately and precisely measured by this new radioimmunoassay. Preliminary results obtained from the measurement of serum leptin in lean, overweight and obese patients are presented. Serum leptin concentrations correlated with body mass index and were significantly higher in women than in men, except for obese patients. (author)

  13. Relationships between changes in leptin and insulin resistance levels in obese individuals following weight loss

    Directory of Open Access Journals (Sweden)

    Tsu-Nai Wang

    2013-08-01

    Full Text Available Obesity can augment insulin resistance (IR, leading to increased risk of diabetes and heart disease. Leptin, ghrelin, and various fatty acids present in the cell membrane may modulate IR. In this study, we aimed to investigate the impact of weight loss on IR, serum leptin/ghrelin levels, and erythrocyte fatty acids, and studied the associations between changes in these variables. A total of 35 obese (body mass index ≥ 27 adults participated in a weight loss program for 3 months. IR was assessed using homeostasis model assessment for insulin resistance (HOMA-IR. The obese participants had a mean weight loss of 5.6 ± 3.8 kg followed by a 16.7% and 23.3% reduction in HOMA-IR and leptin (p  0.05 levels. After adjusting for age, gender, changes in ghrelin, and body fat, we found a significant correlation between decreases in leptin and less risk of no improvement in HOMA-IR levels [odds ratio (OR = 0.69, p = 0.039]. In conclusion, a moderate weight reduction in obese participants over a short period significantly improved IR. This weight reduction concomitantly decreased serum leptin, increased ghrelin, and elevated some erythrocyte unsaturates. Only leptin correlated independently with IR improvement upon multivariable logistic regression analysis, which indicates that leptin may play a role in the modulation of IR following weight loss.

  14. Hormonal and adiposity state of women with polycystic ovary syndrome: implication of adiponectin and leptin

    Directory of Open Access Journals (Sweden)

    Aleksandra Atanasova Boshku

    2016-12-01

    Full Text Available Obesity and insulin resistance are frequently seen comorbidities in patients with polycystic ovary syndrome (PCOS, affecting the already disturbed metabolism of these patients. Disturbed secretion of adiponectin and leptin could be one of the contributing factors of obesity and insulin resistance in patients with PCOS. The aim of this study was to determine the levels of adiponectin and leptin in PCOS patients, as well as their association with other components of the syndrome. This cross-sectional study determined clinical, hormonal, and biochemical markers in 61 women with PCOS and 56 controls. There was a statistically significant difference in adiponectin and leptin between the groups (p>0.001. There was a significant negative correlation between adiponectin, body mass index (BMI, and waist circumference (r= -0.478; -0.452, p<0.001 and a negative correlation with testosterone, free androgen index (FAI, insulin, and the homeostasis model assessment for insulin resistance (HOMA-IR. A positive correlation between adiponectin, sex hormone binding globulin (SHGB, and fasting glucose levels was present. Correlation analysis of leptin with other metabolic parameters showed a positive correlation with BMI, waist circumference, insulin, and HOMA-IR. A significant inverse correlation was present between leptin and SHGB. In conclusion, adiponectin and leptin may serve as potential biomarkers of insulin resistance. Determining levels of adiponectin and leptin in the early course of this syndrome may enable earlier diagnosis of insulin resistance, or even early prevention in PCOS patients.

  15. Thermogenic response and leptin levels rise after recovery of the euthyroid state.

    Science.gov (United States)

    Saraç, F; Ozgen, A Gökhan; Celebi, G; Pehlivan, M; Uluer, H; Yilmaz, C

    2010-04-01

    The aims of the study were to compare: a) the thermogenic responses in subclinical hypothyroidism (SH) and euthyroid state; b) the relationship between thermogenic response and leptin level. Thirty women diagnosed with SH (mean age 39.9+/-4.1 yr; body mass index 23.2+/-2.5 kg/m(2)) were enrolled in the study. Thyroid function tests, leptin, and lipid profiles were measured during SH and after stable euthyroidism was recovered. Thermogenic response was measured by Water Immersion Calorimetry during SH and after the euthyroid state was attained. The mean level of thermogenic response was found to be 1.45+/-0.43 kcal/kg*h in women with SH. It changed to 1.54+/-0.77 kcal/kg*h (p=0.01) in the euthyroid state; the change was statistically significant. Mean level of leptin was found to be 7.22+/-2.6 ng/ml in SH; and 15.8+/-8.0 ng/ml in the euthyroid state. There was a positive correlation between leptin and free T(3) (r=0.460, p=0.009) levels in SH. There were positive correlations between leptin level and fat mass in SH (r=0.820, p=0.01) and in the euthyroid state (r=0.700, p=0.03). No correlations were found between thermogenic response and leptin levels in SH and in the euthyroid state. Thermogenic response and leptin levels rose after the euthyroid state was recovered.

  16. Metabolic state defines the response of rabbit ovarian cells to leptin

    DEFF Research Database (Denmark)

    Harrath, Abdel Halim; Østrup, Olga; Rafay, Jan

    2017-01-01

    and cyclin B1), apoptosis (bax), MAP/ERK1,2 kinase (MAPK), protein kinase A (PKA), and IGF-I. In addition, the release of IGF-I and estradiol (E2) by cells cultured with and without leptin (1, 10, 100, 1000, or 10,000ng/ml) was assessed by radioimmunoassay (RIA). In the granulosa cells of control animals......, leptin promoted cyclin B1, MAPK, and PKA accumulation, but not that of PCNA, and reduced bax and IGF-I accumulation. These cells responded to leptin by increased IGF-I, but not E2 release. In cells of CR animals, leptin increased cyclin B1 accumulation, but decreased PCNA, MAPK, and IGF-I expression. Bax...... and PKA were not affected. Leptin resulted in a decrease in IGF-I release. CR modulated the influence of leptin on E2 release dose dependently, i.e., E2 increased at 10 and decreased at 10,000ng/ml. Therefore, CR modified the influence of leptin on PCNA, E2, bax, PKA, MAPK, and IGF-I release, but it did...

  17. Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.

    Science.gov (United States)

    Kanoski, Scott E; Hayes, Matthew R; Greenwald, Holly S; Fortin, Samantha M; Gianessi, Carol A; Gilbert, Jennifer R; Grill, Harvey J

    2011-08-01

    The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

  18. Serum leptin levels correlation with high blood pressure in adult females

    International Nuclear Information System (INIS)

    Haque, Z.; Shahid, K.U.; Mazahir, I.; Lakho, G.R.; Nafees, M.

    2006-01-01

    To measure serum leptin levels and compare them in lean and obese subjects and to identify correlation between serum leptin levels, heart rate and hypertension in lean and obese subjects among adult females. Seventy female subjects with different body mass indices were selected from OPD of Jinnah Medical and Dental College Hospital (OPD), Karachi. Heart rate was counted manually; blood pressure was measured by mercury sphygmomanometer while serum leptin was measured using enzyme-linked immunoassay. The outcomes hypertension and heart rate were correlated to risk factor leptin. Mean heart rate, systolic and diastolic blood pressure and serum leptin levels of obese people were 90+-1, 142+-2, 89+-1 and 24.13+-1.7 respectively, which were significantly higher as compared to lean subjects (p<0.05). All the parameters correlated positively and significantly with increasing BMI. There was a relationship of tachycardia and hypertension with high serum leptin levels in obesity. Serum leptin levels increase with the level of obesity. Hyper-leptinemia is associated with tachycardia and increases in both systolic and diastolic blood pressure in obesity via complex mechanisms. (author)

  19. Role of Leptin in the Pathogenesis of Reproductive Disorders in Adolescent Girls with Anorexia Nervosa

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    V. O. Andreyeva

    2007-01-01

    Full Text Available Objective: to study a role of leptin in the pathogenesis of reproductive disorders in adolescent girls with anorexia nervosa (AN.Subjects: Two groups of patients the common symptoms of whom were underweight, amenorrhea, the absence of chromosomal or monogenic abnormality. Group 1 consisted of 48 adolescent girls diagnosed as having anorexia nervosa; Group 2 included 41 patients without eating behavioral disorders. A control group comprised 24 patients with a body mass index (BMI of 20.3 (18.5; 24.9 without eating behavioral disorders and with a normal menstrual cycle. Methods: anthropometry, enzyme immunoassay of plasma leptin and neuropeptide Y levels. The statistical validity of group differences was estimated by the Mann-Whitney U-test.Results. There were reductions in the serum content of leptin in patients at an anorectic stage, its hyperproduction at the stage of AN reduction, and no relationship of the leptin concentration to BMI. Hypoleptinemia at the anorectic stage was accompanied by low neuropeptide Y levels. This suggests that resistance to low leptin levels develops, which may be caused by both impaired leptin transport across the blood-brain barrier and hypoinsulinemia.Conclusion. The low levels of leptin and neuropeptide Y at the anorectic stage may be considered to be an adaptive reaction that delays insulin effects in the presence of malnutrition and creates a vicious circle in the regulation of the lipostat system and vicious circle-associated reproductive disorders. 

  20. Leptin-like immunoreactivity in the central nervous system, digestive organs, and gonads of the giant freshwater prawn, Macrobrachium rosenbergii.

    Science.gov (United States)

    Poljaroen, Jaruwan; Tinikul, Yotsawan; Tinikul, Ruchanok; Anurucpreeda, Panat; Sobhon, Prasert

    2017-06-01

    Leptin, a highly conserved adipocyte-derived hormone, plays important roles in a variety of physiological processes, including the control of fat storage and metabolic status which are linked to food intake, energy homeostasis, and reproduction in all vertebrates. In the present study, we hypothesize that leptin is also present in various organs of the fresh water prawns, Macrobrachium rosenbergii. The existence and distribution of a leptin-like peptide in prawn tissues were verified by using Western blotting (WB) and immunohistochemical detection (ID) using primary antibody against human leptin. With WB, a leptin-like peptide, having a molecular weight of 15kDa, was detected in the brain, thoracic ganglia, abdominal ganglia, parts of the gastro-intestinal tract, hepatopancreas, adipocytes and gonads. By ID, leptin immunoreactivity (leptin-ir) was detected in the brain, thoracic ganglia and intersegmental commissural nerve fibers of abdominal ganglia. In the gastrointestinal tract, there was intense leptin-ir in the apical part of the epithelial cells of the cardiac and pyloric parts of the stomach. In the midgut and hindgut, the leptin-ir was detected in epithelial cells and basal cells located near the basal lamina of the epithelium. In addition, there was leptin-ir in the Restzellen cells in the hepatopancreas which produce digestive enzymes. In the ovary, the strong intensity of a leptin-ir was detected in the cytoplasm of middle to late stage oocytes, whereas no positive staining was detected in follicular cells. An intense leptin-ir was detected in spermatocytes and sustentacular cells in the seminiferous tubules in the testes of small and orange claw males. Taken together, the detection of the leptin-ir in several organs implicates the existence of a leptin-like peptide in various organs of the freshwater prawn; and like in vertebrates this peptide may be an important hormonal factor in controlling feeding and reproductive process. Copyright © 2017 Elsevier

  1. Impaired clearance of influenza A virus in obese, leptin receptor deficient mice is independent of leptin signaling in the lung epithelium and macrophages.

    Directory of Open Access Journals (Sweden)

    Kathryn A Radigan

    Full Text Available During the recent H1N1 outbreak, obese patients had worsened lung injury and increased mortality. We used a murine model of influenza A pneumonia to test the hypothesis that leptin receptor deficiency might explain the enhanced mortality in obese patients.We infected wild-type, obese mice globally deficient in the leptin receptor (db/db and non-obese mice with tissue specific deletion of the leptin receptor in the lung epithelium (SPC-Cre/LepR fl/fl or macrophages and alveolar type II cells (LysM-Cre/Lepr fl/fl with influenza A virus (A/WSN/33 [H1N1] (500 and 1500 pfu/mouse and measured mortality, viral clearance and several markers of lung injury severity.The clearance of influenza A virus from the lungs of mice was impaired in obese mice globally deficient in the leptin receptor (db/db compared to normal weight wild-type mice. In contrast, non-obese, SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl had improved viral clearance after influenza A infection. In obese mice, mortality was increased compared with wild-type mice, while the SP-C-Cre+/+/LepR fl/fl and LysM-Cre+/+/LepR fl/fl mice exhibited improved survival.Global loss of the leptin receptor results in reduced viral clearance and worse outcomes following influenza A infection. These findings are not the result of the loss of leptin signaling in lung epithelial cells or macrophages. Our results suggest that factors associated with obesity or with leptin signaling in non-myeloid populations such as natural killer and T cells may be associated with worsened outcomes following influenza A infection.

  2. [Circulating leptin and ghrelin in patients with chronic obstructive pulmonary disease].

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    Peng, Min; Cai, Bai-qiang; Ma, Yi; Zhu, Hui-juan; Sun, Qi; Song, Ai-ling

    2007-03-01

    To investigate the potential roles of leptin and ghrelin in malnutrition in patients with chronic obstructive pulmonary disease (COPD). Plasma leptin, total ghrelin and active ghrelin, TNF-alpha and IL-6 levels were determined in 53 patients with COPD and 26 control subjects. Body compositions were assessed by bioelectrical impedance analysis. Plasma leptin levels were significantly lower in underweight patients than those in normal weight patients and in healthy controls [2.6 (2.0 - 4.4) vs. 6.1 (5.1 - 7.8) vs. 4.8 (3.3 - 6.1) ng/L]. The leptin level was associated positively with fat mass (r = 0.662, P = 0.000) and TNF-alpha (r = 0.431, P = 0.001) in the patients. By a stepwise multiple regression analysis, fat mass, TNF-alpha, presence of COPD, smoking and sex were found to affect leptin level (R(2) = 0.635). Both plasma total ghrelin levels and active ghrelin levels were significantly higher in underweight patients than those in normal weight patients and in healthy controls [total ghrelin: 1090 (860 - 2838) vs. 765 (651 - 941) vs. 844 (676 - 1045) ng/L; active ghrelin: 63 (50 - 97) vs. 47 (41 - 56) vs. 54 (41 - 60) ng/L]. Plasma total ghrelin and active ghrelin were associated negatively with BMI respectively (total ghrelin: r = -0.517, P = 0.000; active ghrelin: r = -0.417, P = 0.002). Plasma leptin levels were decreased, while plasma total ghrelin and active ghrelin levels were elevated in underweight patients with COPD, and the levels were associated with nutritional parameters. The plasma levels of leptin and ghrelin may be a compensatory mechanism in malnutritional status of COPD. After adjustment for nutritional parameters, leptin levels were elevated in COPD patients and correlated to TNF-alpha. The result suggests that leptin may play a role in systemic inflammation of COPD.

  3. Leptin, abdominal obesity and onset of depression in older men and women

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    Milaneschi, Yuri; Simonsick, Eleanor M; Vogelzangs, Nicole; Strotmeyer, Elsa S; Yaffe, Kristine; Harris, Tamara B; Tolea, Magdalena I; Ferrucci, Luigi; Penninx, Brenda W

    2012-01-01

    Objective The mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the “leptin hypothesis” of depression suggests that leptin resistance may be involved in mood regulation. We tested whether high circulatory concentration of leptin, alone and in combination with visceral adiposity, is associated with onset of depression in a sample of older persons. Method Participants were 1220 men and 1282 women aged 70–79 years, enrolled in the Health, Aging and Body Composition study. Plasma concentration of leptin and abdominal visceral fat ascertained by computed tomography were assessed at baseline (April 1997 – June 1998). Onset of depression was defined as a Center for Epidemiological Studies-Depression Scale 10-item score ≥ 10 and/or new antidepressant medication use at any annual visit over a 5-year follow-up. Results Higher leptin was associated with the risk of depression onset in men with high visceral fat (HR=1.25,95%CI=1.06–1.46, p=0.01) but not in those with normal visceral fat (HR=0.98,95%CI=0.80–1.19, p=0.80) (leptin*visceral fat p=0.04). No interaction between leptin and visceral fat was detected in the analysis focusing on women (p=0.90). Conclusion In older men, high leptin was associated with an increased onset of depressive symptoms especially in the presence of abdominal obesity, suggesting that underlying leptin resistance may play a role in this link. Differences in visceral fat levels and metabolic consequences may explain the absence of this association in women. These findings suggest a potential biological link between depression, obesity and their joint association with negative health outcomes. PMID:22687702

  4. Leptin, abdominal obesity, and onset of depression in older men and women.

    Science.gov (United States)

    Milaneschi, Yuri; Simonsick, Eleanor M; Vogelzangs, Nicole; Strotmeyer, Elsa S; Yaffe, Kristine; Harris, Tamara B; Tolea, Magdalena I; Ferrucci, Luigi; Penninx, Brenda W J H

    2012-09-01

    The mechanisms that underlie the association between abdominal obesity and depression risk in older persons are not well known, but the "leptin hypothesis" of depression suggests that leptin resistance may be involved in mood regulation. We tested whether high circulatory concentration of leptin, alone and in combination with visceral adiposity, is associated with onset of depression in a sample of older persons. Participants were 1,220 men and 1,282 women aged 70-79 years and enrolled in the Health, Aging, and Body Composition study. Serum concentration of leptin and abdominal visceral fat, ascertained by computed tomography, were assessed at baseline (April 1997-June 1998). Onset of depression, the primary outcome measure, was defined as a Center for Epidemiologic Studies-depression scale 10-item score ≥ 10 and/or new antidepressant medication use at any annual visit over a 5-year follow-up. Higher leptin level was associated with the risk of depression onset in men with high levels of visceral fat (hazard ratio [HR] = 1.25; 95% CI, 1.06-1.46; P = .01) but not in those with normal visceral fat (HR = 0.98; 95% CI, 0.80-1.19; P = .80) (leptin-by-visceral fat, P = .04). No interaction between leptin and visceral fat was detected in the analysis focusing on women (P = .90). In older men, high leptin level was associated with an increased onset of depressive symptoms, especially in the presence of abdominal obesity, suggesting that underlying leptin resistance may play a role in this link. Differences in visceral fat levels and metabolic consequences may explain the absence of this association in women. These findings suggest a potential biological link between depression, obesity, and their joint association with negative health outcomes. © Copyright 2012 Physicians Postgraduate Press, Inc.

  5. In vivo regulation of intestinal absorption of amino acids by leptin.

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    Fanjul, Carmen; Barrenetxe, Jaione; De Pablo-Maiso, Lorena; Lostao, María Pilar

    2015-01-01

    Leptin is secreted by the gastric mucosa and is able to reach the intestinal lumen and bind to its receptors located in the apical membranes of enterocytes. We have previously demonstrated that apical leptin inhibits uptake of amino acids in rat intestine in vitro and in Caco-2 cells. The aim of the present work was to investigate the effect of leptin on absorption of amino acids using in vivo techniques, which generate situations closer to physiological conditions. In vivo intestinal absorption of amino acids in rats was measured by isolating a jejunal loop and using the single-pass perfusion system. Disappearance of glutamine (Gln), proline (Pro), and β-alanine (β-Ala) from the perfusate, in the absence or presence of leptin, was measured using a radioactivity method. Luminal leptin (25 nM) inhibited the absorption of 2 mM Pro, 5 mM β-Ala, and 5 mM Gln by approximately 45% after 5-15 min; the effect remained constant until the end of the experiment (80 min) and was rapidly and completely reversed when leptin was removed from the perfusion medium. Moreover, leptin was able to regulate the absorption of galactose and Gln in the same animal, indicating a direct action of the hormone on the specific transporters implicated in the uptake of each nutrient. The results of the present work indicate that luminal leptin decreases absorption of amino acids in vivo in a short-term manner and in a reversible way. These results, together with our previous findings, make it evident that leptin can be considered as a hormone which provides the intestine with a control mechanism to handle absorption of nutrients. © 2015 Society for Endocrinology.

  6. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

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    Mokadem, Mohamad; Zechner, Juliet F; Uchida, Aki; Aguirre, Vincent

    2015-01-01

    Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB) induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB. To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet. RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  7. Leptin Is Required for Glucose Homeostasis after Roux-en-Y Gastric Bypass in Mice.

    Directory of Open Access Journals (Sweden)

    Mohamad Mokadem

    Full Text Available Leptin, the protein product of the ob gene, increases energy expenditure and reduces food intake, thereby promoting weight reduction. Leptin also regulates glucose homeostasis and hepatic insulin sensitivity via hypothalamic proopiomelanocortin neurons in mice. Roux-en-Y gastric bypass (RYGB induces weight loss that is substantial and sustained despite reducing plasma leptin levels. In addition, patients who fail to undergo diabetes remission after RYGB are hypoletinemic compared to those who do and to lean controls. We have previously demonstrated that the beneficial effects of RYGB in mice require the melanocortin-4 receptor, a downstream effector of leptin action. Based on these observations, we hypothesized that leptin is required for sustained weight reduction and improved glucose homeostasis observed after RYGB.To investigate this hypothesis, we performed RYGB or sham operations on leptin-deficient ob/ob mice maintained on regular chow. To investigate whether leptin is involved in post-RYGB weight maintenance, we challenged post-surgical mice with high fat diet.RYGB reduced total body weight, fat and lean mass and caused reduction in calorie intake in ob/ob mice. However, it failed to improve glucose tolerance, glucose-stimulated plasma insulin, insulin tolerance, and fasting plasma insulin. High fat diet eliminated the reduction in calorie intake observed after RYGB in ob/ob mice and promoted weight regain, although not to the same extent as in sham-operated mice. We conclude that leptin is required for the effects of RYGB on glucose homeostasis but not body weight or composition in mice. Our data also suggest that leptin may play a role in post-RYGB weight maintenance.

  8. Association between Nitrogen Stable Isotope Ratios in Human Hair and Serum Levels of Leptin.

    Science.gov (United States)

    Ahn, Song Vogue; Koh, Sang-Baek; Lee, Kwang-Sik; Bong, Yeon-Sik; Park, Jong-Ku

    2017-10-01

    Stable isotope ratios have been reported to be potential biomarkers of dietary intake and nutritional status. High serum levels of leptin, a hormone which regulates energy metabolism and food intake, are associated with insulin resistance and metabolic syndrome. However, little is known about the association between stable isotope ratios and the metabolic risk in humans. We investigated whether the carbon and nitrogen stable isotope ratios in hair are associated with serum leptin levels. Hair samples were collected from 399 healthy adults (233 men and 166 women) aged 40 to 70 years of a community-based cohort in Korea and the bulk stable isotope ratios of carbon (δ 13 C) and nitrogen (δ 15 N) were measured for all hair samples. Serum leptin levels were analyzed by radioimmunoassay. δ 15 N showed positive correlations with serum leptin levels. In multivariate models, increasing δ 15 N were associated with elevated serum leptin levels (defined as ≥ the median values), whereas δ 13 C were not significantly associated with serum leptin levels. The odds ratio (95% confidence interval) per 1‰ increase in δ 15 N for an elevated serum leptin level was 1.58 (1.11-2.26). In participants with high body mass index, δ 15 N showed positive associations with serum leptin levels, whereas these associations were not seen in participants with low body mass index. The nitrogen stable isotopic ratio in hair is positively associated with serum leptin levels. The hair δ 15 N could be used as a clinical marker to estimate metabolic risk.

  9. Leptin affects life history decisions in a passerine bird: a field experiment.

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    Mare Lõhmus

    Full Text Available BACKGROUND: Organisms face trade-offs regarding their life-history strategies, such as decisions of single or multiple broods within a year. In passerines displaying facultative multiple breeding, the probability of laying a second clutch is influenced by several life-history factors. However, information about the mechanistic background of these trade-offs is largely lacking. Leptin is a protein hormone produced by white fat cells, and acts as a signal between peripheral energy depots and the central nervous system. In addition, leptin affects cells at all levels of the reproductive axis and plays a critical role in regulating the allocation of metabolic energy to reproduction. As such, it is possible that leptin levels influence the decision of whether or not to invest time and energy into a second clutch. Accordingly, we expect a treatment with exogenous leptin to result in an increased number of second broods. METHODOLOGY/PRINCIPAL FINDINGS: At a later stage during the first brood, female great tits were treated either with long-term leptin-filled cholesterol pellets (the experimental birds or with pellets containing only cholesterol (the control birds. We found that leptin-treated females were significantly more likely to have a second brood and that the earlier females were more likely to lay a second clutch than the late females. CONCLUSIONS/SIGNIFICANCE: As both timing of first brood and treatment with leptin were important in the decision of having multiple broods, the trade-offs involved in the breeding strategy most likely depend on multiple factors. Presumably leptin has evolved as a signal of energy supply status to regulate the release of reproductive hormones so that reproduction is coordinated with periods of sufficient nutrients. This study investigated the role of leptin as a mediator between energy resources and reproductive output, providing a fundamentally new insight into how trade-offs work on a functional basis.

  10. Nutrient and food intake in relation to serum leptin concentration among young Japanese women.

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    Murakami, Kentaro; Sasaki, Satoshi; Takahashi, Yoshiko; Uenishi, Kazuhiro; Yamasaki, Mitsuyo; Hayabuchi, Hitomi; Goda, Toshinao; Oka, Jun; Baba, Keiko; Ohki, Kazuko; Watanabe, Reiko; Sugiyama, Yoshiko

    2007-06-01

    Little is known about the relation of modifiable dietary factors to circulating leptin concentrations, particularly in young adults and non-Western populations. We examined cross-sectional associations between nutrient and food intake and serum leptin concentration in young Japanese women. Subjects were 424 female Japanese dietetic students 18-22 y of age. Intake of macronutrients (protein, total fat; saturated, monounsaturated, and polyunsaturated fatty acids; and carbohydrate), dietary fiber, and 12 food groups was assessed with a validated, self-administered, comprehensive, diet history questionnaire. Fasting blood samples were collected, and serum leptin concentrations were measured by radioimmunoassay. For nutrients, only dietary fiber was a significant determinant of serum leptin concentration. Increasing dietary fiber intake was associated with lower serum leptin concentration independent of potential confounding factors, including body mass index (mean serum leptin concentrations in the lowest and highest quintiles of dietary fiber intake were 8.6 and 7.5 ng/mL, respectively; P for trend = 0.026). Vegetables and pulses were the only foods significantly associated with serum leptin concentration, with higher intakes independently associated with lower concentrations (mean serum leptin concentrations in the lowest and highest quintiles of intake were 8.1 and 7.0 ng/mL, P for trend = 0.007, for vegetables and 8.8 and 7.6 ng/mL, P for trend = 0.019, for pulses, respectively). Intake of dietary fiber, vegetables, and pulses showed an independent inverse association with serum leptin concentration in a group of young Japanese women.

  11. Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows.

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    Ehrhardt, Richard A; Foskolos, Andreas; Giesy, Sarah L; Wesolowski, Stephanie R; Krumm, Christopher S; Butler, W Ronald; Quirk, Susan M; Waldron, Matthew R; Boisclair, Yves R

    2016-05-01

    Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic efficiency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T4 and T3 by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-deficient dairy cow. © 2016 Society for Endocrinology.

  12. Insulin and Leptin Signaling Interact in the Mouse Kiss1 Neuron during the Peripubertal Period.

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    Xiaoliang Qiu

    Full Text Available Reproduction requires adequate energy stores for parents and offspring to survive. Kiss1 neurons, which are essential for fertility, have the potential to serve as the central sensors of metabolic factors that signal to the reproductive axis the presence of stored calories. Paradoxically, obesity is often accompanied by infertility. Despite excess circulating levels of insulin and leptin, obese individuals exhibit resistance to both metabolic factors in many neuron types. Thus, resistance to insulin or leptin in Kiss1 neurons could lead to infertility. Single deletion of the receptors for either insulin or the adipokine leptin from Kiss1 neurons does not impair adult reproductive dysfunction. However, insulin and leptin signaling pathways may interact in such a way as to obscure their individual functions. We hypothesized that in the presence of genetic or obesity-induced concurrent insulin and leptin resistance, Kiss1 neurons would be unable to maintain reproductive function. We therefore induced a chronic hyperinsulinemic and hyperleptinemic state in mice lacking insulin receptors in Kiss1 neurons through high fat feeding and examined the impact on fertility. In an additional, genetic model, we ablated both leptin and insulin signaling in Kiss1 neurons (IR/LepRKiss mice. Counter to our hypothesis, we found that the addition of leptin insensitivity did not alter the reproductive phenotype of IRKiss mice. We also found that weight gain, body composition, glucose and insulin tolerance were normal in mice of both genders. Nonetheless, leptin and insulin receptor deletion altered pubertal timing as well as LH and FSH levels in mid-puberty in a reciprocal manner. Our results confirm that Kiss1 neurons do not directly mediate the critical role that insulin and leptin play in reproduction. However, during puberty kisspeptin neurons may experience a critical window of susceptibility to the influence of metabolic factors that can modify the onset of

  13. Leptin and TNF-alpha levels in patients with chronic obstructive pulmonary disease and their relationship to nutritional parameters.

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    Calikoglu, Mukadder; Sahin, Gulsah; Unlu, Ali; Ozturk, Candan; Tamer, Lülüfer; Ercan, Bahadir; Kanik, Arzu; Atik, Uğur

    2004-01-01

    Leptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. In humans, there was a strong correlation between leptin and nutritional parameters, such as body mass index (BMI) and fat mass (FM). Administration of recombinant leptin to OB/OB mice, which have a genetic defect in leptin production, reduces food intake, increases energy expenditure, and decreases body weight. It is suggested that increased levels of circulating leptin levels may contribute to anorexia and weight loss in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as TNF-alpha. This study aimed to detect serum leptin and TNF-alpha levels in COPD patients without weight loss during stable disease and acute exacerbation, and to investigate relationships between leptin, TNF-alpha and nutritional parameters at different stages of the disease. 26 stable COPD patients, 16 COPD patients with acute exacerbation and 15 control subjects participated in this study. To eliminate the effects of sex differences, all patients and controls were male. BMI, percent ideal body weight, percent FM, sum of skinfold thickness and serum leptin and TNF-alpha levels were measured in all participants. Leptin and TNF-alpha levels were measured by ELISA. Serum leptin and TNF-alpha levels were significantly higher in the patients experiencing exacerbation than in the stable patients and controls. Although leptin levels were lower and TNF-alpha levels were higher in the stable patient group than in the controls, these differences were not statistically different. Leptin levels were significantly correlated with the nutritional parameters in both control and stable groups. However, in patients with acute exacerbation, a correlation between leptin and nutritional parameters was not found. There was no significant relationship between TNF

  14. Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP signaling to inhibit steroidogenesis in human granulosa cells

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    HoYuen Basil

    2009-10-01

    Full Text Available Abstract Background Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells. Methods The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG cells was examined by Enzyme linked immunosorbent assay (ELISA. The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner. Results and Conclusion In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059 and p38 (SB203580 inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone

  15. INFLUENCE OF DIETARY FAT ON LEPTIN AND INSULIN IN MALE ALBINO RATS

    International Nuclear Information System (INIS)

    KASSAB, F.M.A.; ABDEL-KHALEK, L.G.; KAMAL, A.M.

    2008-01-01

    Sixty male albino rats were arranged into 5 equal groups which were used in this study to investigate the relation between leptin and insulin hormones under high fat intake and to assess the role of fresh vegetable intake on minimizing dyslipidemia.The results denoted that dietary fat caused significant increase in the levels of blood glucose and leptin hormone with significant decrease in insulin concentration and with prolonged high fat intake, insulin level was increased. However, the increased leptin and glucose indicated that prolonged fatty diet may cause insulin resistance. Addition of green vegetables to the diet normalized to a great extent the level of cholesterol, triglycerides, VLDL, glucose and insulin

  16. Increased circulating leptin in alcoholic cirrhosis: relation to release and disposal

    DEFF Research Database (Denmark)

    Holst, JJ; Henriksen, Jens Henrik Sahl; Møller, Søren

    1999-01-01

    ). The spillover rates of leptin in cirrhotic patients may be even higher than estimated from the increased systemic veno-arterial gradients. In conclusion, the elevated circulating leptin in patients with cirrhosis is most likely caused by a combination of decreased renal extraction and increased release from...... subcutaneous abdominal, femoral, gluteal, retroperitoneal pelvic, and upper limb fat tissue areas. The hepatosplanchnic bed drained through hepatic veins could not be identified as a source of increased circulating leptin in cirrhosis, but a contribution by the portosystemic collateral flow cannot be excluded....

  17. Weight Perturbation Alters Leptin Signal Transduction in a Region-Specific Manner throughout the Brain

    OpenAIRE

    Morabito, Michael V.; Ravussin, Yann; Mueller, Bridget R.; Skowronski, Alicja A.; Watanabe, Kazuhisa; Foo, Kylie S.; Lee, Samuel X.; Lehmann, Anders; Hjorth, Stephan; Zeltser, Lori M.; LeDuc, Charles A.; Leibel, Rudolph L.

    2017-01-01

    Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minu...

  18. Mitofusin 2 in POMC neurons connects ER stress with leptin resistance and energy imbalance

    DEFF Research Database (Denmark)

    Schneeberger, Marc; Dietrich, Marcelo O; Sebastián, David

    2013-01-01

    Mitofusin 2 (MFN2) plays critical roles in both mitochondrial fusion and the establishment of mitochondria-endoplasmic reticulum (ER) interactions. Hypothalamic ER stress has emerged as a causative factor for the development of leptin resistance, but the underlying mechanisms are largely unknown....... This previously unrecognized role for MFN2 argues for a crucial involvement in mediating ER stress-induced leptin resistance........ Here, we show that mitochondria-ER contacts in anorexigenic pro-opiomelanocortin (POMC) neurons in the hypothalamus are decreased in diet-induced obesity. POMC-specific ablation of Mfn2 resulted in loss of mitochondria-ER contacts, defective POMC processing, ER stress-induced leptin resistance...

  19. Adiponectin and leptin as first trimester markers for gestational diabetes mellitus

    DEFF Research Database (Denmark)

    Thagaard, Ida Näslund; Krebs, Lone; Holm, Jens Christian

    2017-01-01

    Background: Gestational diabetes mellitus (GDM) is increasing partly due to the obesity epidemic. Adipocytokines have thus been suggested as first trimester screening markers for GDM. In this study we explore the associations between body mass index (BMI) and serum concentrations of adiponectin......, leptin, and the adiponectin/leptin ratio. Furthermore, we investigate whether these markers can improve the ability to screen for GDM in the first trimester. Methods: A cohort study in which serum adiponectin and leptin were measured between gestational weeks 6+0 and 14+0 in 2590 pregnant women...

  20. The association of asthma, nasal allergies, and positive skin prick tests with obesity, leptin, and adiponectin

    DEFF Research Database (Denmark)

    Newson, R. B.; Jones, M.; Forsberg, B.

    2014-01-01

    measures of fatness including body mass index and waist/hip ratio, current asthma, and specific skin prick and IgE sensitisation. We used inverse sampling-probability-weighted rank and regression statistics to measure population associations of disease outcomes with adipokines in males and females......, adjusting for confounders (area, age, smoking history, and number of elder siblings) and also mutually adjusting associations with adipokines and fatness measures. ResultsOne thousand nine hundred and fifty-five subjects aged 16-77years had information on leptin or adiponectin levels. Leptin and leptin...

  1. Human breast milk and adipokines--A potential role for the soluble leptin receptor (sOb-R) in the regulation of infant energy intake and development.

    Science.gov (United States)

    Zepf, F D; Rao, P; Moore, J; Stewart, R; Ladino, Yuli Martinez; Hartmann, B T

    2016-01-01

    Concentrations of different adipokines in human breast milk are thought to be able to affect energy intake of the infant. Leptin is a hormone synthesized by adipose tissue and the human placenta and favors satiety. The availability of leptin in breast milk is influenced by epithelial cells of the mammary gland that are known to be able to produce leptin, as well as leptin from maternal circulation that is transported to the breast milk, and which can thus in turn reach neonatal blood after absorption. Research so far as mainly focused on leptin concentrations in breast milk. However, evidence suggests that in addition to leptin concentrations levels of the so-called soluble leptin receptor (sOb-R), the main high-affinity binding protein for leptin in humans, are necessary in order to calculate the free leptin index (FLI) and to assess function of the leptin axis. FLI is calculated from the ratio of leptin to the sOb-R, and serves as the main parameter for assessing function of the leptin axis throughout maturation and development. Here we propose that assessing sOb-R levels in addition to leptin concentrations in breast milk could serve as a valuable tool to investigate effects of the leptin axis in breast milk because sOb-R concentrations can impact available leptin levels, and which in turn can have significant implications for infant energy intake and related development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Age-related changes in acute central leptin effects on energy balance are promoted by obesity.

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    Rostás, I; Tenk, J; Mikó, A; Füredi, N; Soós, S; Solymár, M; Lengyel, A; Székely, M; Gaszner, B; Feller, D; Pétervári, E; Balaskó, M

    2016-12-01

    Leptin is a key catabolic regulator of food intake (FI) and energy expenditure. Both aging and obesity have been shown to induce leptin-resistance. The present study aimed to analyze age-related changes in the anorexigenic and hypermetabolic responsiveness to acute intracerebroventricular leptin administration in different age-groups of normally fed male Wistar rats (adult and old rats from 3 to 24months of age, NF3 to NF24, respectively). The expressions of the long form of the leptin receptor (Ob-Rb) and inhibitory SOCS3 genes were also assessed by quantitative RT-PCR in the arcuate nucleus (ARC). The influence of high-fat diet-induced obesity (HF) on the anorexigenic leptin effects were also tested in younger and older middle-aged groups (HF6 and HF12). Leptin-induced anorexia varied with age: leptin suppressed re-feeding FI (following 48-h fasting) strongly in young adult (NF3), but not in younger or older middle-aged (NF6 or NF12) or in aging (NF18) rats. However, anorexigenic leptin effects reached statistical significance again in old NF24 rats. Leptin-induced hypermetabolism, on the other hand, showed monotonous age-related decline and disappeared by old age. Ob-Rb expression declined until 12months of age followed by a partial recovery in NF18 and NF24 groups. On the other hand, SOCS3 expression was high in NF6 and NF18 and to some extent in NF24 rats. Age-related alterations of Ob-Rb and SOCS3 expression in the ARC may partly contribute to the explanation of age-related variations in anorexigenic but not hypermetabolic leptin effects. High-fat diet-induced obesity was associated with resistance to leptin-induced anorexia in HF6, similar to that seen in NF6. However, instead of the expected leptin-resistance in HF12, a strong leptin-induced suppression of re-feeding was detected in these obese middle-aged rats. Our results suggest that acute central effects of leptin on anorexia and hypermetabolism change in disparate ways during aging, implying separate

  3. Role of leptin during perinatal metabolic programming and obesity.

    Science.gov (United States)

    Djiane, J; Attig, L

    2008-08-01

    The incidence of obesity is rapidly increasing all over the world in epidemic proportions.The epidemia now affects young children and accumulative evidences suggest that the origin of the disease may occur during foetal development and early life. This has introduced the concept of "developmental programming" supported by experimental studies in animal models and numerous epidemiological data. This concept supports the idea that nutritional and hormonal status during pregnancy and early life could interfere irreversibly on the development of the organs involved in the control of food intake and metabolism and particularly the hypothalamic structures responsible of the establishment of the ingestive behaviour and regulation of energy expenditure. The mechanisms responsible of this developmental programming remain poorly documented. However, recent research indicate that the adipokine leptin plays a critical role in this programming.

  4. Placental leptin gene methylation and macrosomia during normal pregnancy.

    Science.gov (United States)

    Xu, Xinyun; Yang, Xinjun; Liu, Ziwei; Wu, Kele; Liu, Zheng; Lin, Chong; Wang, Yuhuan; Yan, Hongtao

    2014-03-01

    The present study examined the placental leptin (LEP) DNA methylation and mRNA levels in macrosomic infants from normal pregnancies. In total, 49 neonates with macrosomia, i.e., high birth weights of ≥ 4,000 g, and 52 neonates with normal birth weights between 2,500 g and 4,000 g were recruited from The Second Affiliated Hospital of Wenzhou Medical University (Wenzhou, Zhejiang) in China. Placental LEP promoter methylation and LEP transcript levels were determined by Sequenom MassARRAY and quantitative PCR, respectively. LEP promoter methylation and mRNA levels were not significantly different between the individuals with macrosomia and the controls. However, stratification revealed that individual CpG dinucleotides were hypermethylated in macrosomia (Pmacrosomia following a normal pregnancy and under certain conditions. However, placental LEP expression was not affected.

  5. Leptin Enhances NR2B-mediated NMDA Responses Via a MAPK-dependent Process in Cerebellar Granule Cells.

    Science.gov (United States)

    Irving, A. J.; Wallace, L; Durakoglugil, D; Harvey, J.

    2006-01-01

    It is well documented that the hormone leptin regulates energy balance via its actions in the hypothalamus. However, evidence is accumulating that leptin plays a key role in numerous CNS functions. Indeed, leptin receptors are expressed in many extrahypothalamic brain regions, with high levels found in the hippocampus and cerebellum. In the hippocampus, leptin has been shown to facilitate NMDA receptor function and modulate synaptic plasticity. A role for leptin in cerebellar function is also indicated as leptin-deficient rodents display reduced mobility that is unrelated to obesity. Here we show that leptin receptor immunolabeling can be detected in cultured cerebellar granule cells, being expressed at the somatic plasma membrane and also concentrated at synapses. Furthermore, leptin facilitated NR2B NMDA receptor-mediated Ca2+ influx in cerebellar granule cells via a mitogen-activated protein kinase-dependent pathway. These findings provide the first direct evidence for a cellular action of leptin in cerebellar neurons. In addition, given that NMDA receptor activity in the cerebellum is crucial for normal locomotor function, these data also have important implications for the potential role of leptin in the control of movement. PMID:16413128

  6. Leptin Boosts Cellular Metabolism by Activating AMPK and the Sirtuins to Reduce Tau Phosphorylation and β-Amyloid in Neurons

    Science.gov (United States)

    Greco, Steven J.; Hamzelou, Ashkan; Johnston, Jane M.; Smith, Mark A.; Ashford, J. Wesson; Tezapsidis, Nikolaos

    2011-01-01

    Leptin is a pleiotropic hormone primarily secreted by adipocytes. A high density of functional Leptin receptors has been reported to be expressed in the hippocampus and other cortical regions of the brain, the physiological significance of which has not been explored extensively. Alzheimer’s disease (AD) is marked by impaired brain metabolism with decreased glucose utilization in those regions which often precede pathological changes. Recent epidemiological studies suggest that plasma Leptin is protective against AD. Specifically, elderly with plasma Leptin levels in the lowest quartile were found to be four times more likely to develop AD than those in the highest quartile. We have previously reported that Leptin modulates AD pathological pathways in vitro through a mechanism involving the energy sensor, AMP-activated protein kinase (AMPK). To this end, we investigated the extent to which activation of AMPK as well as another class of sensors linking energy availability to cellular metabolism, the sirtuins (SIRT), mediate Leptin’s biological activity. Leptin directly activated neuronal AMPK and SIRT in cell lines. Additionally, the ability of Leptin to reduce tau phosphorylation and β-amyloid production was sensitive to the AMPK and sirtuin inhibitors, compound C and nicotinamide, respectively. These findings implicate that Leptin normally acts as a signal for energy homeostasis in neurons. Perhaps Leptin deficiency in AD contributes to a neuronal imbalance in handling energy requirements, leading to higher Aβ and phospho-tau, which can be restored by replenishing low Leptin levels. This may also be a legitimate strategy for therapy. PMID:21945934

  7. The immunohistochemical peptidergic expression of leptin is associated with recurrence of malignancy in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gallina, S; Sireci, F; Lorusso, F; DI Benedetto, D V; Speciale, R; Marchese, D; Costantino, C; Napoli, G; Tessitore, V; Cucco, D; Leone, A; Bonaventura, G; Uzzo, M L; Spatola, G F

    2015-02-01

    Leptin is a peptide that plays a key role in the control of satiety, energy expenditure, food intake and various reproductive processes. In the last years, the expression of leptin had been found in malignant cells of various origins. The aim of this study is to evaluate leptin expression in human laryngeal squamous cell carcinoma (SCC) and to investigate its possible role in predicting prognosis. Leptin expression was determined by immunohistochemistry in pathological and healthy tissue specimens from 24 patients with laryngeal SCC. Specimens were stained with an anti-leptin antibody. All measurements were performed using a computer-based image analysis system and scale of staining intensity was determined. All tumoural specimens showed significant immunoreactivity for leptin compared to healthy tissues (p ≤ 0.05), but showed different immunoreactivity that was related to clinicopathological features. High leptin expression was not significantly related with TNM, histological grading (HG) or advanced (III and IV) clinical stage (p > 0.05). Recurrence of malignancy was found to be significantly related with high expression of leptin by Spearman's rank correlation test (r = 0.59; p = 0.002), Fisher's test (p = 0.017) and Kaplan- Meier product-limit estimate (Log-rank test, p ≤ 0.05). In particular, multivariate logistic regression analysis showed that recurrences were significantly related with nodal involvement, HG and leptin expression (p ≤ 0.05). These preliminary results suggest that leptin may be a valuable parameter for predicting prognosis in laryngeal SCC.

  8. Integral Role of PTP1B in Adiponectin-Mediated Inhibition of Oncogenic Actions of Leptin in Breast Carcinogenesis

    Directory of Open Access Journals (Sweden)

    LaTonia Taliaferro-Smith

    2013-01-01

    Full Text Available The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a “guardian angel adipocytokine” for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B, which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast

  9. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis.

    Science.gov (United States)

    Taliaferro-Smith, LaTonia; Nagalingam, Arumugam; Knight, Brandi Brandon; Oberlick, Elaine; Saxena, Neeraj K; Sharma, Dipali

    2013-01-01

    The molecular effects of obesity are mediated by alterations in the levels of adipocytokines. High leptin level associated with obese state is a major cause of breast cancer progression and metastasis, whereas adiponectin is considered a "guardian angel adipocytokine" for its protective role against various obesity-related pathogenesis including breast cancer. In the present study, investigating the role of adiponectin as a potential inhibitor of leptin, we show that adiponectin treatment inhibits leptin-induced clonogenicity and anchorage-independent growth. Leptin-stimulated migration and invasion of breast cancer cells is also effectively inhibited by adiponectin. Analyses of the underlying molecular mechanisms reveal that adiponectin suppresses activation of two canonical signaling molecules of leptin signaling axis: extracellular signal-regulated kinase (ERK) and Akt. Pretreatment of breast cancer cells with adiponectin protects against leptin-induced activation of ERK and Akt. Adiponectin increases expression and activity of the physiological inhibitor of leptin signaling, protein tyrosine phosphatase 1B (PTP1B), which is found to be integral to leptin-antagonist function of adiponectin. Inhibition of PTP1B blocks adiponectin-mediated inhibition of leptin-induced breast cancer growth. Our in vivo studies show that adenovirus-mediated adiponectin treatment substantially reduces leptin-induced mammary tumorigenesis in nude mice. Exploring therapeutic strategies, we demonstrate that treatment of breast cancer cells with rosiglitazone results in increased adiponectin expression and inhibition of migration and invasion. Rosiglitazone treatment also inhibits leptin-induced growth of breast cancer cells. Taken together, these data show that adiponectin treatment can inhibit the oncogenic actions of leptin through blocking its downstream signaling molecules and raising adiponectin levels could be a rational therapeutic strategy for breast carcinoma in obese patients

  10. Maternal characteristics associated with milk leptin content in a sample of Filipino women and associations with infant weight for age.

    Science.gov (United States)

    Quinn, Elizabeth A; Largado, Fe; Borja, Judith B; Kuzawa, Christopher W

    2015-05-01

    Human milk contains many metabolic hormones that may influence infant growth. Milk leptin is positively associated with maternal adiposity and inversely associated with infant growth. Most research has been conducted in populations with higher leptin levels; it is not well understood how milk leptin may vary in lean populations or the associations that reduced leptin may have with infant size for age. It is also largely unknown if associations between maternal body composition and milk leptin persist past 1 year of age. We investigated the association between maternal body composition and milk leptin content in a sample of lean Filipino women and the association between milk leptin content and infant size for age. Milk samples were collected at in-home visits from 113 mothers from Cebu, Philippines. Milk leptin content was measured using EIA techniques; anthropometric data, dietary recalls, and household information were also collected. Mean ± standard deviation (SD) milk leptin in this sample was 300.7 ± 293.6 pg/mL, among the lowest previously reported. Mean ± SD maternal percentage body fat was 24.8% ± 3.5%. Mean ± SD infant age was 9.9 ± 7.0 months, and mean ± SD weight for age z-score was -0.98 ± 1.06. Maternal percentage body fat was a significant, positive predictor of milk leptin content. Milk leptin was a significant, inverse predictor of infant weight and body mass index z-scores in infants 1 year old or younger. The association between maternal body composition, milk leptin, and infant growth persists in mothers with lean body composition. Milk leptin is not associated with growth in older infants. © The Author(s) 2014.

  11. Elevated serum leptin levels are associated with good nutritional status in non-obese chronic hemodialysis patients.

    Science.gov (United States)

    Kara, Ekrem; Ahbap, Elbis; Sahutoglu, Tuncay; Sakaci, Tamer; Basturk, Taner; Koc, Yener; Sevinc, Mustafa; Akgol, Cuneyt; Ucar, Zuhal Atan; Kayalar, Arzu Ozdemir; Bayraktar, Feyza; Unsal, Abdulkadir

    2015-03-01

    Leptin is a hormone and a proinflammatory cytokine secreted from adipocytes, which functions to suppress appetite in healthy persons. Serum leptin levels are significantly elevat