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Growth factor deficiency in adulthood constitutes a distinct clinical syndrome with significant morbidities including abnormal body composition, reduced energy, affective disturbances, dyslipidemia, and increased cardiovascular risk. Protein replacement therapies using recombinant proteins or enzymes represent the only approved treatment. Combinatorial antibodies have shown great promise as a new class of therapeutic molecules because they act as “mechanism‐based antibodies” with both agonist and antagonist activities. Using leptin, a key hormone in energy metabolism, as an example, a function‐guided approach is developed to select combinatorial antibodies with high potency and full agonist activity that substitute natural growth factors in vivo. The identified antibody shows identical biochemical properties and cellular profiles as leptin, and rescues leptin‐deficiency in ob/ob mice. Remarkably, the antibody activates leptin receptors that are otherwise nonfunctional because of mutations (L372A and A409E). Combinatorial antibodies have significant advantages over recombinant proteins for chronical usage in terms of immunological tolerance and biological stability., A full agonist antibody against leptin receptor is discovered using a function‐guided approach from a combinatorial antibody library. It shows identical biochemical properties and functional profiles as leptin both in vitro and in vivo. Furthermore, it activates several leptin receptor mutants which cannot be activated by leptin, indicating promising therapeutic applications. The selection strategy can be applied to other cellular targets.

The aim of this study was to investigate the effect of serum leptin in rats performing various duration swimming exercises. In the study, 30 healthy albino wistar male rats with an average weight of 180-220 grams were divided into 5 groups including; control, water exercises, 15, 30 and 60 minutes swimming groups. Animals were swim-exercised for 90 days. At the end of 90 days, after performed urethane anesthesia, blood samples were taken by intracardiac way. Collected blood was analysed according to procedures. Data were analyzed by using SPSS 15. One-way anova and tukey multiple comparison test were performed in the study. The homogeneity of the variances was examined by Levene's statistic. Results showed that the leptin levels were as follows: control (1480,00 pg/ml), water exercise (705,83 pg/ml), 15 (602,33 pg/ml), 30 (396,67 pg/ml) and 60 (435,83 pg/ml). Statistically significant difference was found between control and 30 minutes swimming group (p=0,012) and control and 60 minutes swimming group (p=0,017) (p

Background: 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. 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 leptin index were calculated using the General Additive Model for Location Scale and Shape (GAMLSS). Results: 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). Conclusion: 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.

The adipokine leptin signals the body’s nutritional status to the brain, and particularly, the hypothalamus. However, leptin receptors (LEPRs) can be found all throughout the body and brain, including the pituitary. It is known that leptin is permissive for reproduction, and mice that cannot produce leptin (Lep/Lep) are infertile. Many studies have pinpointed leptin’s regulation of reproduction to the hypothalamus. However, LEPRs exist at all levels of the hypothalamic–pituitary–gonadal axis. We have previously shown that deleting the signaling portion of the LEPR specifically in gonadotropes impairs fertility in female mice. Our recent studies have targeted this regulation to the control of gonadotropin releasing hormone receptor (GnRHR) expression. The hypotheses presented here are twofold: (1) cyclic regulation of pituitary GnRHR levels sets up a target metabolic checkpoint for control of the reproductive axis and (2) multiple checkpoints are required for the metabolic signaling that regulates the reproductive axis. Here, we emphasize and explore the relationship between the hypothalamus and the pituitary with regard to the regulation of GnRHR. The original data we present strengthen these hypotheses and build on our previous studies. We show that we can cause infertility in 70% of female mice by deleting all isoforms of LEPR specifically in gonadotropes. Our findings implicate activin subunit (InhBa) mRNA as a potential leptin target in gonadotropes. We further show gonadotrope-specific upregulation of GnRHR protein (but not mRNA levels) following leptin stimulation. In order to try and understand this post-transcriptional regulation, we tested candidate miRNAs (identified with in silico analysis) that may be binding the Gnrhr mRNA. We show significant upregulation of one of these miRNAs in our gonadotrope-Lepr-null females. The evidence provided here, combined with our previous work, lay the foundation for metabolically regulated post-transcriptional control of the gonadotrope. We discuss possible mechanisms, including miRNA regulation and the involvement of the RNA binding protein, Musashi. We also demonstrate how this regulation may be vital for the dynamic remodeling of gonadotropes in the cycling female. Finally, we propose that the leptin receptivity of both the hypothalamus and the pituitary are vital for the body’s ability to delay or slow reproduction during periods of low nutrition.

WOS: 000416207600017, The in vitro embryo culture systems need further improvement to enhance the efficiency of bovine embryo production. Growth factors play key roles in embryo production and quality. The objective of this study was to define the effects of leptin, insulin-like growth factor-1 (IGF-1), and their combination on embryonic development, apoptosis, and expression profiles of a panel of developmentally important genes during 8-day embryo culture. The oocytes were aspirated from slaughterhouse ovaries of mixed breed cows. Following IVM/IVF presumptive zygotes were obtained. To accomplish this objective, presumptive zygotes (16-18 h post-insemination) were cultured in vitro as control (no supplementation, n = 349), 5 ng/ml leptin (Group I, n = 322), 100 ng/ml IGF-1 (Group II, n = 347), and 5 ng/ml leptin and 100 ng/ml IGF-1 (Group III, n = 360). All groups were supplemented with 10% fetal calf serum (FCS) on Day 4, and blastocysts were harvested on day 8. The DNA-fragmented nuclei of blastocyst were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and expression profiles of a panel of developmentally important genes were assayed by real-time polymerase chain reaction (RT-PCR). The cleavage rate and embryo development to 8-16 cell stage were higher in groups II and III as compared to control (P < 0.05), respectively. Percentage of blastocyst and mean cell numbers per blastocyst did not differ among the groups. Addition of IGF-I and/or combination with leptin decreased the number of nuclei with fragmented DNA (P < 0.01) as compared to the control group. Although the expression of glucose transporter 1 (Glut1), desmosomal glycoprotein desmocollin III (DcIII), and insulin like growth factor 2 receptor (Igf2r) transcripts did not change among the groups, interferon-tau (IF-tau) and DNA methyltransferase 3A (Dnmt3a) were down-regulated in group II while heat shock protein-70 (Hsp70) and IF-tau were up regulated in group III. Results indicate that addition of IGF-I in culture media improved the cleavage rate; combination with leptin also improved the development rates to 8-16-cell-stage embryos, decreased the TUNEL-positive nuclei, and caused alterations in the amounts of transcripts for the developmentally important genes assayed., University of Wisconsin-Madison College of Agriculture and Life Sciences; Mississippi Agriculture Forestry and Experiment Station, USA; IDB; University of Selcuk, Konya, Turkey, Authors would like to thank Mr. Brad Haley for help in obtaining bovine ovaries and Mr. Peter Crump for statistical analysis of the data. Research was supported by the University of Wisconsin-Madison College of Agriculture and Life Sciences, and by Mississippi Agriculture Forestry and Experiment Station, USA. A. Kaya was supported by IDB and by University of Selcuk, Konya, Turkey.

Backdround/Aims: The aim of this work was to study the effect and mechanism of action of leptin added apically, on glucose absorption, using Caco-2 cells as a model. Methods: Cells were grown on inserts and treated with leptin, at different time points after confluence. Radiolabelled glucose was added to the upper chamber and samples from the lower chamber were collected and assayed for radioactivity. Results: Glucose absorption increased with an increase in the level of differentiation and was associated with an increase in the protein expression level of glucose transporters. Leptin reduced glucose absorption only by day 16 after confluence, the time at which apical leptin receptors started appearing. This inhibitory effect became higher the longer the post confluence period, and was prominent on day 23. The hormone effect was found to be mediated via a decrease in the number of glucose transporters (SGLT1 and GLUT2) and a decrease in the activity of the Na+/K+ ATPase which was assayed by measuring the amount of inorganic phosphate liberated in presence and absence of enzyme activators. Conclusion: It was concluded that by day 23 post confluence, Caco-2 cells are differentiated and are appropriate to use as a model for intestinal transport studies.

Several studies support the relation between leptin and Alzheimer’s disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons. Similar translocation of leptin was found in brains from Tg2576 and apoE4 mice. Moreover, an enhancement of leptin receptors was found in hippocampus of young Tg2576 mice and in primary astrocytes and neurons treated with Ab1-42. In contrast, old Tg2576 mice showed decreased leptin receptors levels. Similar findings to those seen in Tg2576 mice were found in apoE4, but not in apoE3 mice. These results suggest that leptin levels are intact, but leptin signalling is impaired in AD. Thus, Ab accumulation and apoE4 genotype result in a transient enhancement of leptin signalling that might lead to a leptin resistance state over time.

Aim. To determine the prevalence of mononucleotide leptin receptor gene LEPR Q223R polymorphism in patients having coronary heart disease (CHD) with postinfarction cardiosclerosis depending on type 2 diabetes comorbidity.Materials and methods. 147 patients having stable CHD with postinfarction cardiosclerosis (100% male), the average age of 52, were examined. In 64 (43.5%) patients CHD combined with type 2 diabetes. The CHD diagnosis was established by АНА/АСС (2014) and ESC (2013) recommendations. LEPR Q223R (Gln223Arg, rs1137101) gene polymorphism was determined using allele-specific polymerase chain reaction in real time.Results and discussion. In the group of patients having CHD with postinfarction cardiosclerosis (Podillya region inhabitants) the frequency of LEPR Q223R gene genotypes was as follows: QQ – 25.2 %, QR – 42.4 %, RR – 32.7 %. The frequency of R allele in patients having CHD was significantly higher than in the practically healthy group, and was 53.7 to 41.3% (χ2=4.72, р=0.03). Сomorbidity chances significantly increase in R allele carriers (OR=1.58, 95 % СІ 0.99-2.53), while Q allele carrier state have a protective value (OR=0.63, 95 % СІ 0.40-1.01). RR genotype associated with CHD earlier debut, higher frequency of Q- myocardial infarction (OR=4.3; 95 % СІ 1.51-12.5) and heart failure progression (OR=3.60; 95 % СІ 1.67-7.77).Conclusion. RR genotype LEPR Q223R gene carrier state is a potential unmodified factor that accelerates development and increases the severity of CHD, associated with type 2 diabetes, in males, Метою роботи було встановити поширеність однонуклеотидного поліморфізму гену лептинових рецепторів LEPR Q223R у хворих на ішемічну хворобу серця (ІХС) з післяінфарктним кардіосклерозом залежно від коморбідності з ЦД 2 типу. Результати отримані в когортах хворих показали, що носійство генотипу RR гену LEPR Q223R є потенційним немодифікованим чинником, який прискорює розвиток та підвищує важкість перебігу ІХС, асоційованої з ЦД 2 типу, у чоловіків

In Sprague-Dawley rats, brown adipose tissue (BAT) thermogenesis occurs in an episodic ultradian manner (BAT on-periods) as part of the basic rest-activity cycle (BRAC). Eating occurs approximately 15 min after the onset of BAT on-periods. Zucker obese (fa/fa) rats eat larger less frequent meals than control rats. In chronically instrumented conscious unrestrained Zucker obese rats we examined ultradian fluctuations in BAT, body and brain temperatures, and the relation between BAT temperature and eating. The interval between BAT temperature peaks for the 12 hour dark phase was 121 ± 3 (mean ± SE) min for Zucker obese rats and 91 ± 3 min for control lean rats (p < 0.01). Corresponding values for the light phase were 148 ± 6 and 118 ± 4 min (p < 0.01). Mean BAT and body temperatures were lower in Zucker obese rats, in comparison with lean controls, during both BAT on-periods and BAT off-periods. Mean brain temperatures were lower during BAT off-periods. Amplitudes of the BRAC-related increases in all 3 temperatures were greater in the Zucker obese rats. Meal onset in Zucker obese rats commenced 15 ± 1 min after the onset of a BAT on-period, not significantly different for the delay observed in lean control rats (18 ± 1 min, p > 0.05). Thus periods between eating are increased in the Zucker obese rats, but the action of leptin, absent in these animals, is not crucial for the timing of eating in relation to increases in BAT and body temperature. Lack of the normal excitatory action of leptin on brain-regulated BAT sympathetic discharge could also contribute to lower BAT thermogenesis in Zucker obese rats. Refereed/Peer-reviewed

The role of leptin and its receptors (OBRs) in the pathogenesis of various primary human malignancies has been demonstrated. However, their expression and clinicopathological significance in papillary thyroid cancer (PTC) is not fully understood. In this study, we examined the expression of leptin and OBRs in 76 PTC samples using immunohistochemistry, and their associations with clinicopathological parameters were evaluated. The expression of OBRs was observed in the tumor cell membrane and/or cytoplasm, with a positive rate of 73.7% (56/76), while leptin was expressed in the tumor cell cytoplasm in 55 of 76 cases (72.4%). The expression of either protein was associated with greater tumor size (P=0.016 for leptin and P=0.002 for OBRs). In addition, the expression levels of leptin and OBRs were associated with each other. Neither leptin nor OBR expression levels were associated with other parameters, including age, body weight, postmenopausal state, multifocality and lymph node metastasis. These data suggest that the expression of leptin and/or OBRs in PTC is associated with tumor size and may be a potential target in PTC.

WOS: 000299580800011, PubMed: 22082804, Background: Leptin and adiponectin receptors mediate the role of leptin in stimulating the growth of leukemic cells and the protective function of adiponectin undertaken in several malignancies such as leukemia. In this study, we investigated the involvement of the expression of leptin and adiponectin receptors in chronic myeloid leukemia (CML) pathogenesis. Methods: The expression of leptin receptor isoforms, OB-Rt, OB-Ra, and OB-Rb, and the expression of adiponectin receptors, AdipoR1 and AdipoR2, were measured as mRNA levels in two CML cell lines (K562 and Meg-01) and 20 CML patients and 24 healthy controls by using RT-PCR. Results: OB-Rt and OB-Ra isoforms expression of the leptin receptors were found to be significantly lower in Meg-01 cell lines than K562 cells. All leptin receptors were downregulated in CML patients and more particularly OB-Rb level was found to be undetectably low in normal PBMC as well as in CML patients. AdipoR1 expression level was higher in Meg-01 than in K562, whereas AdipoR2 level was found to be unchanged in both cell lines. Interestingly, while AdipoR1 expression increased in CML patients, AdipoR2 decreased. Moreover, imatinib therapy did not affect both leptin and adiponectin isoform expressions. Conclusion: While the decrease in leptin receptor levels in CML patients was confirmed, the increase in AdipoR1 levels and relevant decrease in AdipoR2 levels depicted their possible involvement in CML pathogenesis. This suggests different functions of adiponectin receptors in CML development. (C) 2011 Elsevier Ltd. All rights reserved., Gulhane Military Medical Academy, This work was supported by Gulhane Military Medical Academy Research Fund.

Leptin is an adipocyte-derived cytokine that regulates body weight mainly via the long form of the leptin receptor (Ob-Rb). Leptin and its receptors are expressed in several tissues, suggesting that leptin might also be effective peripherally. We hypothesized that, as shown in taste cells, leptin and its receptors isoforms (Ob-Rs) could be present in the rat olfactory mucosa (OM). Using RT-PCR, light and electron microscopy immunohistochemistry (ICC), we found that different isoforms of the receptor were expressed in OM and localized in sustentacular cells and in a subpopulation of maturating neurons; in addition, immunoreactivity was also present in differentiated neurons and enriched at the cilia membranes, where the odorants bind to their receptors. Moreover, using RT-PCR, ICC and RIA measurements, we showed that leptin is synthesized locally in the olfactory mucosa. In addition, we demonstrate that fasting causes a significant enhanced transcription of both leptin and Ob-Rs in rat OM by quantitative RT-PCR data. Altogether, these results strongly suggested that leptin, acting as an endocrine or a paracrine factor, could be an important regulator of olfactory function, as a neuromodulator of the olfactory message in cilia of mature olfactory receptors neurons (ORN), but also for the homeostasis of this complex tissue, acting on differentiating neurons and on sustentacular cells.

Kolorektalni karcinom je multifaktorska bolest koja je posledica interakcije nasljednih i faktora okoline. Brojne studije su potvrdile značajnu povezanost ovog tumora sa navikama u ishrani, a zapaženo je da je rizik za nastanak kolorektalnog karcinoma kod gojaznih osoba 1,5-3,5 puta veći u poređenju sa normalno uhranjenim osobama. Ključni molekul u razvoju gojaznosti je leptin, produkt gena gojaznosti (ob-gena), koji djeluje preko svojih receptora (LEPR). CILj: Određivanje ekspresije leptin receptora (LEPR) i korelacija ekspresije LEPR sa proliferacijom, neoangiogenezom i sekrecijom mucina u kolorektalnom adenokarcinomu. METOD: Za istraživanje je korišćen biopsijski, operativni materijal dobijen resekcijom kolorektalnog karcinoma od 75 pacijenata lečenih na Hirurškoj klinici Kliničkog Centra Crne Gore (KCCG). Za diferencijaciju histopatoloških procesa je korišćena rutinska H&E metoda,a za ispitivanje ekspresije LEPR, markera proliferacije Ki67 i ekspresije markera angiogeneze Endoglina (CD105) je korišćena imunohistohemijska ABC metoda sa specifičnim antitijelima. Za diferencijaciju mucina korištene su histohemijske AB-PAS i HID-AB (pH 2,5) tehnike.Za svaki pojedinačan slučaj određeni su klasični prognostički parametri:stadijum tumora, histološki gradus,prisutnost limfatičke, angio- i perineuralne invazije, prisustvo metastaza u limfnim nodusima i jetri, stepen dezmoplazije , nekroze i inflamacijskog infiltrata..Nakon kvantitativne analize ekspresije LEPR, stereometrijski je izračunata gustina Ki67 pozitivnih ćelija i gustina mikrovaskularnih struktura po mm2,a zatim i kvalitativna i semikvantitativna analiza ekspresije neutralnih, sijalo- i sulfomucina. Dobijene vrijednosti su korištene za određivanje prognostičkog značaja ekspresije leptin receptora u odnosu na stepen proliferacije, mikrovaskularnu gustinu, ekspresiju mucina, kao i u odnosu na klasične kliničke prognostičke parametre tumora. REZULTATI:Umjerena i izražena ekspresija LEPR je nađena u signifikantnom broju slučajeva (77.3%) kolorektalnog adenokarcinoma. Umjerena i izražena sekrecija sijalomucina je nađena u 88% slučajeva kolorektalnog karcinoma. U najvećem broju slučajeva ovog tumora verifikovana je asekrecija fukomucina dok je sekrecija sulfomucina najčešće bila prisutna u tragu. Ekspresija LEPR je visoko značajnim i visoko pozitivnim koeficijentima korelacije povezana sa indeksom nuklearnog proliferativnog antigena (proIDX) i indeksom neoangiogeneze (mvdIDX).Osim indeksa proliferacije i neoangiogeneze, visoko značajnim koeficijentima korelacije sa LEPR ekspresijom su povezane i apsolutne vrijednosti ekspresije Ki67 i Endoglina (CD105). Druga po značaju je veza između ekspresije LEPR i histohemijske ekspresije slabo kisjelih sijalomucina.Povećanje ekspresije LEPR je visoko značajnim pozitivnim koeficijentom korelacije povezano sa hipersekrecijom sijalomucina. Negativnim, ali statistički značajnim koeficijentom korelacije je LEPR ekspresija u vezi sa sekrecijom jako kisjelih sulfomucina. Umjereno visokim i statistički visoko značajnim koeficijentima korelacije ekspresija LEPR je povezana sa stadijumom tumora po Astler-Coller klasifikaciji, sa metastazama zahvaćenim limfnim čvorovima, perineuralnom invazijom i udaljenim metastazama. ZAKLjUČAK:Porast ekspresije LEPR je praćen povećanjem proliferativne aktivnosti, povećanom neoangiogenezom, aberacijama u mucinskoj produkciji i porastom metastatskog potencijala kolorektalnog adenokarcinoma. Colorectal carcinoma is multifactorial disease which is a consequence of interreaction between hereditary and enviromental factors. Numerous studies have confirmed significant linkage of this tumor with food intake habits, and it was observed that the risk for development of colorectal carcinoma in obese persons is 1,5-3,5 folds greater compared to normal weight persons. Key molecule in obesity development is leptin, product of obesity gene (ob), that acts through its receptors (LEPR). AIM:Determination of LEPR expression and correlation of LEPR expression with proliferation, neoangiogenesis and mucin secretion in colorectal carcinoma. METHODS: For research, we have used biopsies obtained from resected colorectal carcinomas from 75 patients treated in Clinic for Surgery of Clinical Center of Montenegro (CCMNE). For differentiation of histopathological processes,routine H&E method was used, and for investigation of LEPR expression, and expression of proliferation (Ki67) and angiogenesis marker (CD105),it has been used immunohistochemical ABC method with specific antibodies. For mucin differentiation, histochemical AB-PAS and HID-AB (pH 2,5) were used. For each single case were used classic prognostic parameters: tumor stage, histologic grade, presence of lymphatic, angio and perineural invasion, presence of metastasis in lymph nodes and liver, desmoplasia grade, necrosis and inflamation infiltrate. After quantitative analysis of LEPR expression, the density of Ki67 positive cells and density of microvascular structures per square milimeter was calculated stereometrically. Subsequently, qualitative and semiquantitative analisys of neutral, sialo and sulfomucins expression was performed. Obtained values were used for determination of prognostic significance of LEPR expression ragarding the degree of proliferation, microvascular density, mucin expression, and regarding the classic clinical prognostic parameters as well. RESULTS: Moderate and pronounced LEPR expression was found in significant number of cases (77,3%) of colorectal carcinoma. Moderate and pronounced secretion of sialomucins was found in 88% of colorectal carcinoma cases. In majority of this tumor cases,no secretion of fucomucins was verified, while sulfomucins secretion was most often present in trace. LEPR expression is with highly significant and highly positive correlation coeficients related to nuclear proliferative antigen index (proIDX) and neoangiogenesis index (mvdIDX). Besides proliferation and neoangiogenesis index, with highly significant correlation coeficients, LEPR expression is related to absolute values of Ki67 and Endoglin (CD105). Second by significance,is relation between LEPR expression and histochemical expression of weak acid sialomucins. Increasing of LEPR expression is with highly significant positive correlation coeficient related to sialomucins hypersecretion. With negative, but statistically significant correlation coeficient, LEPR expression is related to sulfomucins secretion. With moderate and statistically highly significant correlation coeficients, LEPR expression was related to tumor stage according to Astler-Coller classification, metastatic lymph nodes,perineural invasion and distant metastasis. CONCLUSION: Increasing of LEPR expression is followed by increasing of proliferative activity, increased neoangiogenesis, abberations of mucin production and increasing of metastatic potential of colorectal adenocarcinoma.

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

WOS: 000351056100052 PubMed: 25422229 Introduction: Human adiponectin (ApN) is a 30 kDa glycoprotein of 244-amino acids which is extensively produced by adipocytes. ApN acts via two receptors, namely adiponectin receptor-1 (Adipo-R1) and adiponectin receptor-2 (Adipo-R2). Studies have shown the presence of Adipo-R1 and Adipo-R2 expression immunohistochemically in human colorectal cancers (CRCs). However, only a few studies exist which investigated effects of adiponectin receptor expression on CRC characteristics. Objectives: In the present study, we aimed to explore Adipo-R1/-R2 expression in human colorectal cancers and any association with clinicopathological characteristics and survival. Materials and Methods: The study enrolled 58 colorectal cancer patients with tumor resection and a control group of 30 subjects with normal colon mucosa. Results: Positivity for Adipo-R1/-R2 expression was significantly more common in the control group in comparison to the patient group (both p

Bu çalışma, 26 Nisan 2003 tarihinde Lyon[Fransa]'da düzenlenen 6. European Congress of Endocrinology'de bildiri olarak sunulmuştur. To examine serum leptin concentrations in obese and lean patients with polycystic ovary syndrome (PCOS) to assess whether the changes in leptin levels are due to obesity or hormonal alterations. Controlled clinical study. Academic research environment. Obese and lean women with PCOS. Blood samples were collected before and after food consumption. Serum leptin and insulin levels. Serum leptin concentrations were significantly correlated with body mass index (r = 0.649) and also with HOMA (r = 0.535). However, after controlling for body mass index in a partial correlation analysis, no significant correlation was found between serum leptin levels and HOMA or hyperinsulinemia. While lean patients with PCOS had a significant correlation between leptin concentrations and obesity parameters, they did not show any significant correlation with insulin resistance parameters. Although leptin concentrations in women with PCOS correlate with insulin resistance/hyperinsulinemia, this is related only to obesity.

Leptin is a regulatory protein from adipokines family, that maintain energy homeostasis of the body and deter obesity development. Impaired transfer of leptin signals to hypothalamus leads to leptin resistance and its adverse complications. Understanding of leptin resistance mechanisms is pivotal for the development of preventive and treatment procedures aiming to decrease the risk of atherosclerosis

International audience; Food odours are major determinants for food choice, and their detection depends on nutritional status. The effects of different odour stimuli on both behavioural responses (locomotor activity and sniffing) and Fos induction in olfactory bulbs (OB) were studied in satiated or 48-h fasted rats. We focused on two odour stimuli: isoamyl acetate (ISO), as a neutral stimulus either unknown or familiar, and food pellet odour, that were presented to quiet rats during the light phase of the day. We found significant effects of nutritional status and odour stimulus on both behavioural and OB responses. The locomotor activity induced by odour stimuli was always more marked in fasted than in satiated rats, and food odour induced increased sniffing activity only in fasted rats. Fos expression was quantified in periglomerular, mitral and granular OB cell layers. As a new odour, ISO induced a significant increase in Fos expression in all OB layers, similar in fasted and satiated rats. Significant OB responses to familiar odours were only observed in fasted rats. Among the numerous peptides shown to vary after 48 h of fasting, we focused on orexins (for which immunoreactive fibres are present in the OB) and leptin, as a peripheral hormone linked to adiposity, and tested their effects of food odour. The administration of orexin A in satiated animals partially mimicked fasting, since food odour increased OB Fos responses, but did not induce sniffing. The treatment of fasted animals with either an orexin receptors antagonist (ACT-078573) or leptin significantly decreased both locomotor activity, time spent sniffing food odour and OB Fos induction in all cell layers, thus mimicking a satiated status. We conclude that orexins and leptin are some of the factors that can modify behavioural and OB Fos responses to a familiar food odour. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Since its discovery in 1922, insulin has been thought to be required for normal metabolic homeostasis and survival. However, this view would need to be revised as recent results from different laboratories have convincingly indicated that life without insulin is possible in rodent models. These data indicate that particular neuronal circuitries, which include hypothalamic leptin-responsive neurons, are empowered with the capability of permitting life in complete absence of insulin. Here, we review the neuronal and peripheral mechanisms by which leptin signaling in the central nervous system (CNS) regulates glucose metabolism in an insulin-independent manner.

BACKGROUND AND AIM: Leptin, a hormone mainly produced by fat cells, acts primarily on the hypothalamus regulating energy expenditure and food intake. Leptin receptors are expressed in several tissues and the possible physiological role of leptin is being extensively investigated, with the result that important peripheral actions of the hormone in the organism are being discovered. Recent studies have demonstrated leptin and leptin receptor expression in gastric epithelial cells. In the present study, we report the presence of the long leptin receptor isoform (OB-Rb) in human, rat, and mouse small intestine, supporting the hypothesis of leptin as a hormone involved in gastrointestinal function. METHODS: The presence of the leptin receptor was determined by immunocytochemical methods using antibodies against the peptide corresponding to the carboxy terminus of the long isoform of the leptin receptor. Human duodenal biopsies from normal individuals undergoing gastrointestinal endoscopy, and intestinal fragments of Wistar rats and Swiss mice were processed for the study. RESULTS: Immunoreactivity for the long leptin receptor isoform was observed in the three studied species. Staining was located throughout the cytoplasm of the enterocytes, of both villi and crypts, and in the basolateral plasma membrane. Immunolabelling for OB-Rb protein was also found in the brush border of human enterocytes of formol and paraformaldehyde fixed samples. CONCLUSION: This report demonstrates the presence of the long leptin receptor isoform in the absorptive cells of rat, mouse, and human small intestine, suggesting that leptin could have a physiological role in the regulation of nutrient absorption.

Purpose: Leptin plays an important role in the control of body weight and also has a growth-factor-like function in epithelial cells. Abnormal expression of leptin and leptin receptor may be associated with cancer development and progression. We evaluated the relationship among leptin and leptin receptors polymorphisms, body mass index (BMI), serum leptin concentrations, and clinicopathologic features with gastric cancer and determined whether they could be the risk factor of gastric cancer. Methods: We measured the serum leptin concentrations of 48 Korean patients with gastric cancer and 48 age- and sex-matched controls. By polymerase chain reaction-restriction fragment length polymorphism, we investigated one leptin gene promoter G-2548A genotype and four leptin receptor gene polymorphisms at codons 223, 109, 343, and 656. Results: There was no significant difference between the mean leptin concentrations of the patient and control groups, while BMI was significantly lower in gastric cancer cases (22.9 ± 3.6 vs. 24.5 ± 2.8 ㎏/㎡, P = 0.021). There was significant association between the LEPR Lys109Arg genotype and gastric cancer risk, heterozygotes for GA genotype had been proved to increased the risk of gastric cancer, and its corresponding odds ratio was 2.926 (95% confidence interval, 1.248 to 6.861). Conclusion: Our results suggested that LEPR gene Lys109Arg polymorphism is associated with gastric cancer in Korean patients.

OBJECTIVE: Obesity is a complex multifactorial disease that is often associated with cardiac arrhythmias. Various animal models have been used extensively to study the effects of obesity on physiological functions, but, to our knowledge, no study related to ionic membrane currents has been performed on isolated cardiac myocytes. Therefore, we examined the electrophysiological characteristics of four ionic currents from isolated left ventricular myocytes of a high-energy (HE)-induced obesity rat model. RESEARCH METHODS AND PROCEDURES: Male Sprague-Dawley rats were fed with either a control diet or a diet containing 33% kcal as fat (HE) for 14 weeks starting at 6 weeks of age. Voltage-clamp experiments were performed on ventricular myocytes. Leptin receptor (ObR) expression was measured using ObR enzyme-linked immunosorbent assay. RESULTS: In the HE group, rats designated as obese did not develop a cardiac hypertrophy, either at the organ level or at the cellular level. Densities and kinetics of the L-type calcium current, the transient outward potassium current, the delayed rectifier potassium current, and the sodium-calcium exchange current (I(NCX)) were not significantly different between control and obese rats. A down-regulation of ObR expression was evidenced in the heart of obese rats compared with controls. Acute exposure (5 minutes) of leptin (100 nM) did not induce a significant modification in the current densities either in control or in obese rats, except for I(NCX) density measured in control rats. DISCUSSION: The absence of effect of leptin on I(NCX) in obese rats could be a potential arrhythmogenic substrate in obesity.