WorldWideScience

Sample records for leptin decreases food

  1. Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake.

    Science.gov (United States)

    Mars, Monica; de Graaf, Cees; de Groot, Lisette C P G M; Kok, Frans J

    2005-03-01

    The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

  2. Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake

    NARCIS (Netherlands)

    Mars, M.; Graaf, de C.; Groot, de C.P.G.M.; Kok, F.J.

    2005-01-01

    The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric

  3. Modulation of leptin resistance by food compounds.

    Science.gov (United States)

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

    2016-08-01

    Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring.

    Science.gov (United States)

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D'mello, Anil P

    2016-04-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal protein restriction during pregnancy and lactation on food consumption, central leptin sensitivity, bone health, and susceptibility to high fat diet-induced adiposity in 1-year-old male offspring. Sprague-Dawley rats received either a control or a protein restricted diet throughout pregnancy and lactation and pups were weaned onto laboratory chow. One-year-old low protein (LP) offspring exhibited hyperphagia. The inability of an intraperitoneal (i.p.) leptin injection to reduce food intake indicated that the hyperphagia was mediated by decreased central leptin sensitivity. Hyperphagia was accompanied by lower body weight suggesting increased energy expenditure in LP offspring. Bone density and bone mineral content that are negatively regulated by leptin acting via the sympathetic nervous system (SNS), were decreased in LP offspring. LP offspring did not exhibit increased susceptibility to high fat diet induced metabolic effects or adiposity. The results presented here indicate that the programming effects of perinatal protein restriction are mediated by specific decreases in central leptin signalling to pathways involved in the regulation of food intake along with possible enhancement of different CNS leptin signalling pathways acting via the SNS to regulate bone mass and energy expenditure. © 2016 John Wiley & Sons Australia, Ltd.

  5. 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.

  6. Leptin and zinc relation : In regulation of food intake and immunity

    Directory of Open Access Journals (Sweden)

    Abdulkerim Kasim Baltaci

    2012-01-01

    Full Text Available Leptin is synthesized and released by the adipose tissue. Leptin, which carries the information about energy reserves of the body to the brain, controls food intake by acting on neuropeptide Y (NPY, which exercises a food-intake-increasing effect through relevant receptors in the hypothalamus. Zinc deficiency is claimed to result in anorexia, weight loss, poor food efficiency, and growth impairment. The fact that obese individuals have low zinc and high leptin levels suggests that there is a relation between zinc and nutrition, and consequently also between zinc and leptin. Leptin deficiency increases the predisposition to infections and this increase is associated with the impairments in the production of cytokines. Zinc has a key role in the sustenance of immune resistance against infections. Dietary zinc deficiency negatively affects CD +4 cells, Th functions, and consequently, cell-mediated immunity by causing a decrease in the production of IL-2, IF-γ, and TNF-α, which are Th1 products. The relation between zinc and the concerned cytokines in particular, and the fact that leptin has a part in the immune responses mediated by these cytokines demonstrate that an interaction among cellular immunity, leptin and zinc is inevitable. An overall evaluation of the information presented above suggests that there are complex relations among food intake, leptin and zinc on one hand and among cellular immunity, leptin and zinc on the other. The aim of the present review was to draw attention to the possible relation between zinc and leptin in dietary regulation and cellular immunity.

  7. Leptin promoter gene polymorphism on -2549 position decreases plasma leptin and increases appetite in normal weight volunteers

    Directory of Open Access Journals (Sweden)

    Sandra Bragança Coelho

    2014-05-01

    Full Text Available Introduction: Investigate whether polymorphism in the promoter region encoding leptin and leptin receptor gene, in normal weight individuals, affects hormonal and appetite responses to peanuts.Materials and methods: Appetite, anthropometric indices, body composition, physical activity, dietary intake and leptin, ghrelin and insulin levels were monitored. Polymorphism analyses were also carried out.Results: None of the treatments led to statistical differences in the analyzed hormones. No polymorphism was found for leptin receptor gene, while for leptin gene, 50% of the volunteers presented one polymorphic allele and 13% presented both polymorphic alleles. These last ones presented lower body fat mass, leptin and ghrelin plasma concentrations, and fullness rates. They also presented higher hunger, desire to eat, and desire to eat sweet and salty foods.Conclusions: Peanut did not affect appetite and presented no different hormonal responses, compared to other foods studied. Polymorphic allele carriers in both alleles presented higher probability to develop obesity. However, the magnitude of this probability could not be measured.

  8. 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.

  9. The effects of leptin on REM sleep and slow wave delta in rats are reversed by food deprivation.

    Science.gov (United States)

    Sinton, C M; Fitch, T E; Gershenfeld, H K

    1999-09-01

    Leptin (ob protein) is an adipose tissue derived circulating hormone that acts at specific receptors in the hypothalamus to reduce food intake. The protein is also critically involved in energy balance and metabolic status. Here the effect of leptin on sleep architecture in rats was evaluated because food consumption and metabolic status are known to influence sleep. Sprague-Dawley rats were chronically implanted with electrodes for EEG and EMG recording and diurnal sleep parameters were quantified over 9-h periods following leptin administration. Murine recombinant leptin (rMuLep) was administered systemically to rats that either had undergone 18 h of prior food deprivation or had received food ad libitum. In the normally fed rats, leptin significantly decreased the duration of rapid eye movement sleep (REMS) by about 30% and increased the duration of slow wave sleep (SWS) by about 13%, the latter effect reflecting enhanced power in the delta frequency band. These results are consistent with studies that have linked changes in metabolic rate with effects on sleep. Leptin administration has previously been shown to alter neuroendocrine parameters that could have mediated these changes in sleep architecture. Unexpectedly, prior food deprivation negated the effect of leptin on both REMS and SWS, a result that emphasizes the significance of the apparent coupling between sleep parameters and energy status.

  10. Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the Lou/C rat.

    Directory of Open Access Journals (Sweden)

    Christelle Veyrat-Durebex

    Full Text Available The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3 ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3, known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF and thyrotropin-releasing hormone (TRH.

  11. Changes in children's sleep duration on food intake, weight, and leptin.

    Science.gov (United States)

    Hart, Chantelle N; Carskadon, Mary A; Considine, Robert V; Fava, Joseph L; Lawton, Jessica; Raynor, Hollie A; Jelalian, Elissa; Owens, Judith; Wing, Rena

    2013-12-01

    To examine the effect of experimental changes in children's sleep duration on self-reported food intake, food reinforcement, appetite-regulating hormones, and measured weight. Using a within-subjects, counterbalanced, crossover design, 37 children, 8 to 11 years of age (27% overweight/obese) completed a 3-week study. Children slept their typical amount at home for 1 week and were then randomized to either increase or decrease their time in bed by 1.5 hours per night for 1 week, completing the alternate schedule on the third week. Primary outcomes were dietary intake as assessed by 24-hour dietary recalls, food reinforcement (ie, points earned for a food reward), and fasting leptin and ghrelin. The secondary outcome was child weight. Participants achieved a 2 hour, 21 minute difference in the actigraph defined sleep period time between the increase and decrease sleep conditions (P fasting morning leptin values (P food reinforcement or in fasting ghrelin. Compared with decreased sleep, increased sleep duration in school-age children resulted in lower reported food intake, lower fasting leptin levels, and lower weight. The potential role of sleep duration in pediatric obesity prevention and treatment warrants further study.

  12. The administration of long-term high-fat diet in ovariectomized wistar rat (Study on Daily Food Intake, Lee Index, Abdominal Fat Mass and Leptin Serum Levels)

    OpenAIRE

    Fitriani, Dita; Meliala, Andreanyta; Agustiningsih, Denny

    2016-01-01

    Background: Leptin and estrogen are the hormone that has an important function in energy homeostasis through anorexic effects on the central nervous system. Leptin and estrogen action can decrease food intake, increases energy expenditure and thermogenesis. However, the administration of long-term high-fat diet can lead to impaired leptin function. In addition, estrogen deficiency is also considered a risk factor that may increase the occurrence of obesity in menopause. Objective: This st...

  13. Leptin actions on food intake and body temperature are mediated by IL-1

    OpenAIRE

    Luheshi, Giamal N.; Gardner, Jason D.; Rushforth, David A.; Loudon, Andrew S.; Rothwell, Nancy J.

    1999-01-01

    Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, inje...

  14. Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats.

    Science.gov (United States)

    Bruijnzeel, Adrie W; Corrie, Lu W; Rogers, Jessica A; Yamada, Hidetaka

    2011-06-01

    There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15-500 ng/side) or Arc (15-150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005-5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake. Published by Elsevier B.V.

  15. Leptin actions on food intake and body temperature are mediated by IL-1.

    Science.gov (United States)

    Luheshi, G N; Gardner, J D; Rushforth, D A; Loudon, A S; Rothwell, N J

    1999-06-08

    Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, injection of leptin increased levels of the proinflammatory cytokine IL-1beta in the hypothalamus of normal Sprague-Dawley rats. Central injection of IL-1 receptor antagonist (IL-1ra) inhibited the suppression of food intake caused by central or peripheral injection of leptin (60 and 84%, respectively) and abolished the leptin-induced increase in body temperature in both cases. Mice lacking (gene knockout) the main IL-1 receptor (80 kDa, R1) responsible for IL-1 actions showed no reduction in food intake in response to leptin. These data indicate that leptin actions in the brain depend on IL-1, and we show further that the effect of leptin on fever, but not food intake, is abolished by a cyclooxygenase inhibitor. Thus, we propose that in addition to its role in body weight regulation, leptin may mediate neuroimmune responses via actions in the brain dependent on release of IL-1 and prostaglandins.

  16. Food deprivation and leptin prioritize ingestive and sex behavior without affecting estrous cycles in Syrian hamsters.

    Science.gov (United States)

    Schneider, Jill E; Casper, Janelle F; Barisich, Amanda; Schoengold, Candace; Cherry, Sandeep; Surico, Justine; DeBarba, Ashley; Fabris, Frank; Rabold, Elizabeth

    2007-03-01

    Energy consumption is critical for the energetically expensive processes related to reproduction, and thus, mechanisms that increase ingestive behavior are directly linked to reproductive success. Similarly, the mechanisms that inhibit hunger and ingestive behavior might be most adaptive when these mechanisms cause individuals to stop foraging, hoarding and eating in order to find and court potential mates. In the laboratory, ingestive behaviors are typically studied separately from reproductive behaviors even though it is likely that these behaviors evolved under conditions in which both food and mates were available. We examined the choice between paracopulatory and ingestive behaviors in a semi-natural environment in which both food and potential mates were available. Intact female Syrian hamsters showed a high preference for males on days 3 and 4 (day 4 being the day of ovulation and estrous behavior), and a 48-h period of food deprivation significantly decreased preference for sex and increased preference for eating and food hoarding on day 3 in 89% of the hamsters, although none became anestrous. The same period of food deprivation significantly decreased the level of vaginal marking without significant effects on plasma estradiol concentrations. Next, hamsters were either food deprived (FD) or fed ad libitum, and half of each group was treated with vehicle or the adipocyte hormone leptin. The percentage of females with a low preference for sex was significantly greater in the FD compared to the ad libitum-fed groups, and leptin treatment prevented this effect. Metabolic fuels, possibly acting through leptin and other hormones, might influence sensitivity to estradiol or enhance the downstream effects of estradiol, thereby increasing motivation for sex and decreasing the relative motivation to forage, hoard and eat food.

  17. Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex.

    Science.gov (United States)

    Kroemer, Nils B; Wuttig, Franziska; Bidlingmaier, Martin; Zimmermann, Ulrich S; Smolka, Michael N

    2015-07-01

    Endocrine signals such as ghrelin and leptin are known to modulate the mesocorticolimbic dopaminergic system and, consequently, show associations with food and drug reward. In animal models, nicotine was demonstrated to reduce body weight by attenuating food intake and effects of leptin and ghrelin are partly modulated by nicotinic acetylcholine receptors which hint at potential interactions. However, the neuropharmacological modulation of endocrine signals by nicotine in healthy humans remains to be tested experimentally. We used functional magnetic resonance imaging to investigate food-cue reactivity after an overnight fast and following a caloric load (oral glucose tolerance test, OGTT) in 26 healthy normal-weight never-smokers. Moreover, we administered either nicotine (2 mg) or placebo gums using a randomized cross-over design and assessed blood plasma levels of ghrelin and leptin. During fasting, nicotine administration decreased correlations with ghrelin levels in the mesocorticolimbic system whereas correlations with leptin were increased. After the OGTT, nicotine increased the modulatory effects of ghrelin and leptin on food-cue reactivity, particularly in the ventromedial prefrontal cortex (vmPFC) and the amygdala. Critically, this led to an indirect modulation of the behavioral 'appetizer effect' (i.e. cue-induced increases in subjective appetite) by homeostatic feedback signals via food-cue reactivity in vmPFC. We conclude that nicotine enhances the effect of ghrelin and leptin in the valuation and relevance network which might, in turn, reduce appetite. This highlights that amplifying the impact of homeostatic signals such as ghrelin and leptin in normal-weight individuals might hint at a mechanism contributing to nicotine's anorexic potential. © 2014 Society for the Study of Addiction.

  18. Apelin-13 increased food intake with serum ghrelin and leptin levels in male rats.

    Science.gov (United States)

    Saral, S; Alkanat, M; Sumer, A; Canpolat, S

    2018-01-01

    In this study, we aimed to explain the role of apelin-13 on body weight, food and water intake with serum leptin, ghrelin, neuropeptid Y (NPY) and peptid YY (PYY) levels in male rat. Thirty-two Sprague-Dawley male rats were used for the study. The rats were injected SP (0.9 %) intraperitoneally (i.p) in the control group and 30 (AP30), 100 (AP100) and 300 (AP300) µg/kg apelin-13 in the study groups, respectively, 10 min before the transition to dark period, for 10 days. During the experimental period, with light and dark periods of food and water intake, body weights were recorded in rats. Rats were euthanized and serum samples were obtained. In serum samples leptin, ghrelin, NPY and PYY levels were measured with specific ELISA kit. Apelin-13 was increased body weights in all three (AP30, AP100 and AP300) groups compared with the control group. AP100 and AP300 groups had increased food intake in the dark and the cumulative period, but in the light period food intake values were not significantly increased (p > 0.05). As for the value of water intake, compared with the control group, all dose of apelin-13 increased water intake during the dark and the cumulative period. There was no significant change in water intake in the light period. On the other hand, compared with the control group, serum leptin levels were found to increase in the groups administered 100 and 300 µg/kg of apelin-13 (p Ghrelin levels were found high in all groups treated with apelin-13. Serum levels of NPY decreased only in the 300 µg/kg apelin-13 treated group (p 0.05). Apelin-13 increases body weight in rats as well as food and water intake (dark and cumulative period). Additionally, ghrelin can mediate the orexigenic effect of apelin-13 in the regulation of food intake (Fig. 4, Ref. 37).

  19. Food additives such as sodium sulphite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro.

    Science.gov (United States)

    Ciardi, Christian; Jenny, Marcel; Tschoner, Alexander; Ueberall, Florian; Patsch, Josef; Pedrini, Michael; Ebenbichler, Christoph; Fuchs, Dietmar

    2012-03-01

    Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment.

  20. Essential Role for Hypothalamic Calcitonin Receptor‒Expressing Neurons in the Control of Food Intake by Leptin.

    Science.gov (United States)

    Pan, Warren; Adams, Jessica M; Allison, Margaret B; Patterson, Christa; Flak, Jonathan N; Jones, Justin; Strohbehn, Garth; Trevaskis, James; Rhodes, Christopher J; Olson, David P; Myers, Martin G

    2018-04-01

    The adipocyte-derived hormone leptin acts via its receptor (LepRb) on central nervous system neurons to communicate the repletion of long-term energy stores, to decrease food intake, and to promote energy expenditure. We generated mice that express Cre recombinase from the calcitonin receptor (Calcr) locus (Calcrcre mice) to study Calcr-expressing LepRb (LepRbCalcr) neurons, which reside predominantly in the arcuate nucleus (ARC). Calcrcre-mediated ablation of LepRb in LepRbCalcrknockout (KO) mice caused hyperphagic obesity. Because LepRb-mediated transcriptional control plays a crucial role in leptin action, we used translating ribosome affinity purification followed by RNA sequencing to define the transcriptome of hypothalamic Calcr neurons, along with its alteration in LepRbCalcrKO mice. We found that ARC LepRbCalcr cells include neuropeptide Y (NPY)/agouti-related peptide (AgRP)/γ-aminobutyric acid (GABA) ("NAG") cells as well as non-NAG cells that are distinct from pro-opiomelanocortin cells. Furthermore, although LepRbCalcrKO mice exhibited dysregulated expression of several genes involved in energy balance, neither the expression of Agrp and Npy nor the activity of NAG cells was altered in vivo. Thus, although direct leptin action via LepRbCalcr cells plays an important role in leptin action, our data also suggest that leptin indirectly, as well as directly, regulates these cells.

  1. 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

  2. No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Bienert, Petr; Tomandl, Josef; Forejt, Martin; Vavrina, Martin; Kudelkova, Jana; Vasku, Anna

    2008-02-01

    Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

  3. Reconstruction of the drive underlying food intake and its control by leptin and dieting

    NARCIS (Netherlands)

    Grasman, J.

    2013-01-01

    The intake of food and the expenditure of calories is modelled by a system of differential equations. The state variables are the amount of calories stored in adipose tissue and the level of plasma leptin. The model has as input a drive that controls the intake of food. This drive consists of a

  4. Leptin signaling in the medial nucleus tractus solitarius reduces food seeking and willingness to work for food.

    Science.gov (United States)

    Kanoski, Scott E; Alhadeff, Amber L; Fortin, Samantha M; Gilbert, Jennifer R; Grill, Harvey J

    2014-02-01

    The adipose-derived hormone leptin signals in the medial nucleus tractus solitarius (mNTS) to suppress food intake, in part, by amplifying within-meal gastrointestinal (GI) satiation signals. Here we show that mNTS leptin receptor (LepRb) signaling also reduces appetitive and motivational aspects of feeding, and that these effects can depend on energy status. Using the lowest dose that significantly suppressed 3-h cumulative food intake, unilateral leptin (0.3 μg) administration to the mNTS (3 h before testing) reduced operant lever pressing for sucrose under increasing work demands (progressive ratio reinforcement schedule) regardless of whether animals were energy deplete (food restricted) or replete (ad libitum fed). However, in a separate test of food-motivated responding in which there was no opportunity to consume food (conditioned place preference (CPP) for an environment previously associated with a palatable food reward), mNTS leptin administration suppressed food-seeking behavior only in chronically food-restricted rats. On the other hand, mNTS LepRb signaling did not reduce CPP expression for morphine reinforcement regardless of energy status, suggesting that mNTS leptin signaling differentially influences motivated responding for food vs opioid reward. Overall results show that mNTS LepRb signaling reduces food intake and appetitive food-motivated responding independent of energy status in situations involving orosensory and postingestive contact with food, whereas food-seeking behavior independent of food consumption is only reduced by mNTS LepRb activation in a state of energy deficit. These findings reveal a novel appetitive role for LepRb signaling in the mNTS, a brain region traditionally linked with processing of meal-related GI satiation signals.

  5. Leptin concentrations in response to acute stress predict subsequent intake of comfort foods

    Science.gov (United States)

    Tomiyama, A. Janet; Schamarek, Imke; Lustig, Robert H.; Kirschbaum, Clemens; Puterman, Eli; Havel, Peter J.; Epel, Elissa S.

    2012-01-01

    Both animals and humans show a tendency toward eating more “comfort food” (high fat, sweet food) after acute stress. Such stress eating may be contributing to the obesity epidemic, and it is important to understand the underlying psychobiological mechanisms. Prior investigations have studied what makes individuals eat more after stress; this study investigates what might make individuals eat less. Leptin has been shown to increase following a laboratory stressor, and is known to affect eating behavior. This study examined whether leptin reactivity accounts for individual differences in stress eating. To test this, we exposed forty women to standardized acute psychological laboratory stress (Trier Social Stress Test) while blood was sampled repeatedly for measurements of plasma leptin. We then measured food intake after the stressor in 29 of these women. Increasing leptin during the stressor predicted lower intake of comfort food. These initial findings suggest that acute changes in leptin may be one of the factors modulating down the consumption of comfort food following stress. PMID:22579988

  6. Serum triglycerides, but not cholesterol or leptin, are decreased in suicide attempters with mood disorders.

    Science.gov (United States)

    da Graça Cantarelli, Maria; Nardin, Patrícia; Buffon, Andréia; Eidt, Murilo Castilhos; Antônio Godoy, Luiz; Fernandes, Brisa S; Gonçalves, Carlos-Alberto

    2015-02-01

    Many peripheral biomarkers, including low cholesterol and its fractions, have been examined to identify suicidal behavior. Herein, we assessed serum lipid profile and some proteins putatively associated with suicidal behavior in subjects with mood disorder (bipolar disorder or major depressive disorder) with a recent suicide attempt and with no lifetime history of suicide attempts. Fifty subjects had presented an episode of attempted suicide during the last 15 days, and 36 subjects had no history of any suicide attempt. We measured total cholesterol, HDL, LDL and triglycerides as well as serum leptin, brain-derived neurotrophic factor (BDNF), S100B and C-reactive protein (CRP). Individuals that had attempted suicide presented decreased body mass index (BMI) and waist circumference. After adjusting for these confounders, we found that triglycerides were decreased in attempted suicide subjects. We found no differences among total cholesterol, LDL, and HDL or leptin, S100B, CRP and BDNF. This is a cross-sectional study, and we cannot therefore assess whether a decrease in triglycerides caused a mood episode with suicidal ideation that led to a suicide attempt or if the presence of a mood episode originated a loss of appetite and consequent loss of weight, therefore decreasing triglyceride levels. These results do not support the hypothesis that lower levels of cholesterol are associated with suicidal behavior in a mood disorder sample. However, our data support the idea that adiposity is differentiated in these patients (reduced BMI, waist circumference and serum triglycerides), which could lead to an altered communication between the adipose tissue and brain. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

    Science.gov (United States)

    Yehuda-Shnaidman, Einav; Nimri, Lili; Tarnovscki, Tanya; Kirshtein, Boris; Rudich, Assaf; Schwartz, Betty

    2013-01-01

    Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, prespiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues. PMID:24073224

  8. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review.

    NARCIS (Netherlands)

    Klok, M.D.; Jakobsdottir, S.; Drent, M.L.

    2007-01-01

    Leptin and ghrelin are two hormones that have been recognized to have a major influence on energy balance. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a

  9. 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

  10. The administration of long-term high-fat diet in ovariectomized wistar rat (Study on Daily Food Intake, Lee Index, Abdominal Fat Mass and Leptin Serum Levels

    Directory of Open Access Journals (Sweden)

    Dita Fitriani

    2016-12-01

    Conclusion: Serum leptin levels positively correlated with Lee index and abdominal fat mass, but negatively correlated with daily food intake. Administration of long-term high-fat diet in this study cannot induce leptin resistance.

  11. 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.

  12. Puberty Is Delayed in Male Mice With Dextran Sodium Sulfate Colitis Out of Proportion to Changes in Food Intake, Body Weight, and Serum Levels of Leptin

    OpenAIRE

    DEBOER, MARK D.; LI, YONGLI

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the ...

  13. Puberty is delayed in male mice with dextran sodium sulfate colitis out of proportion to changes in food intake, body weight, and serum levels of leptin.

    Science.gov (United States)

    Deboer, Mark D; Li, Yongli

    2011-01-01

    In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.

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

    Science.gov (United States)

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

    2001-01-01

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

  15. Leptin is associated with exaggerated brain reward and emotion responses to food images in adolescent obesity.

    Science.gov (United States)

    Jastreboff, Ania M; Lacadie, Cheryl; Seo, Dongju; Kubat, Jessica; Van Name, Michelle A; Giannini, Cosimo; Savoye, Mary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia; Sinha, Rajita

    2014-11-01

    In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors. Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption. Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE). This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D. © 2014 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.

  16. Stop signals decrease choices for palatable foods through decreased food evaluation

    Science.gov (United States)

    Veling, Harm; Aarts, Henk; Stroebe, Wolfgang

    2013-01-01

    The present study explores whether presenting specific palatable foods in close temporal proximity of stop signals in a go/no-go task decreases subsequent evaluations of such foods among participants with a relatively high appetite. Furthermore, we tested whether any decreased evaluations could mediate subsequent food choice. Participants first received a go/no-go task in which palatable foods were consistently linked to go cues or no-go cues within participants. Next, evaluation of the palatable foods was measured as well as food choice. Replicating previous work, results show that among participants with a relatively high appetite palatable foods associated with no-go cues are less often chosen as snacks compared to when these foods are associated with go cues, whereas this manipulation did not affect participants with a relatively low appetite. Moreover, this effect was completely mediated by decreased evaluation of the palatable foods that had been associated with the no-go cues, whereas evaluation of the foods associated with go cues did not mediate this effect. Results further showed that the devaluation effect of foods associated with no-go cues was independent of the amount of pairings (4 vs. 12 vs. 24) with the no-go cues. The current findings suggest that decreased food evaluation is a mechanism that explains effects of stop signals on food choice. PMID:24324451

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

    Science.gov (United States)

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

    2001-01-01

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

  18. The effects of leptin in combination with a cannabinoid receptor 1 antagonist, AM 251, or cannabidiol on food intake and body weight in rats fed a high-fat or a free-choice high sugar diet.

    Science.gov (United States)

    Wierucka-Rybak, M; Wolak, M; Bojanowska, E

    2014-08-01

    High intake of fats and sugars has prompted a rapid growth in the number of obese individuals worldwide. To further investigate whether simultaneous pharmacological intervention in the leptin and cannabinoid system might change food and water intake, preferences for palatable foods, and body weight, we have examined the effects of concomitant intraperitoneal administration of leptin and AM 251, a cannabinoid 1 (CB1) receptor antagonist, or cannabidiol (CBD), a plant cannabinoid, in rats maintained on either a high-fat (HF) diet (45% energy from fat) or free-choice (FC) diet consisting of high-sucrose and normal rat chow (83% and 61% energy from carbohydrates, respectively). Leptin at a dose of 100 μg/kg injected individually for 3 subsequent days to rats fed a HF diet reduced significantly the daily caloric intake and inhibited body weight gain. The hormone had no significant effects, however, on either caloric intake, body weight or food preferences in rats fed an FC diet. Co-injection of leptin and 1 mg/kg AM 251 resulted in a further significant decrease in HF diet intake and a profound reduction in body weight gain both in HF diet- and FC diet-fed rats. This drug combination, however, had no effect on the consumption of high-sucrose chow. In contrast, 3mg/kg of CBD co-injected with leptin did not modify leptin effects on food intake in rats maintained on an FC or HF diet. None of the drug combinations affected water consumption. It is concluded that the concomitant treatment with leptin and AM 251 attenuated markedly body weight gain in rats maintained on high-calorie diets rich in fat and carbohydrates but did not affect preferences for sweet food.

  19. THE EFFECTS OF EXERCISE ON FOOD INTAKE AND HUNGER: RELATIONSHIP WITH ACYLATED GHRELIN AND LEPTIN

    Directory of Open Access Journals (Sweden)

    Serife Vatansever-Ozen

    2011-06-01

    Full Text Available This study investigated the effects of a long bout of aerobic exercise on hunger and energy intake and circulating levels of leptin and acylated ghrelin. Ten healthy male subjects undertook two, 4 h trials in a randomized crossover design. In the exercise trial subjects ran for 105 min at 50% of maximal oxygen uptake and the last 15 min at 70% of maximal oxygen uptake followed by a 120 min rest period. In the control trial, subjects rested for 4 h. Subjects consumed a buffet test meal at 180 min during each trial. Hunger ratings, acylated ghrelin, leptin, glucose and insulin concentrations were measured at 0, 1, 2, 3 and 4 h. No differences were found at baseline values for hunger, acylated ghrelin, leptin, insulin and glucose for both trials (p > 0.05. The estimated energy expenditure of the exercise trial was 1550 ± 136 kcal. Exercise did not change subsequent absolute energy intake, but produced a significant decrease (p < 0.05 in relative energy intake. A two-way ANOVA revealed a significant (p < 0. 05 interaction effect for hunger and acylated ghrelin. In conclusion, this exercise regimen had a positive effect on reducing appetite which is related to reduced acylated ghrelin responses over time. This finding lends support for a role of exercise in weight management

  20. Transport across the blood-brain barrier of pluronic leptin.

    Science.gov (United States)

    Price, Tulin O; Farr, Susan A; Yi, Xiang; Vinogradov, Serguei; Batrakova, Elena; Banks, William A; Kabanov, Alexander V

    2010-04-01

    Leptin is a peptide hormone produced primarily by adipose tissue that acts as a major regulator of food intake and energy homeostasis. Impaired transport of leptin across the blood-brain barrier (BBB) contributes to leptin resistance, which is a cause of obesity. Leptin as a candidate for the treatment of this obesity is limited because of the short half-life in circulation and the decreased BBB transport that arises in obesity. Chemical modification of polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block copolymers (Pluronic) is a promising technology to improve efficiency of delivery of polypeptides to the brain. In the present study, we determined the effects of Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance, stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when injected intracerebroventricularly after overnight food deprivation and 125I-leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was administered via tail vein in normal body weight mice [0-30 min, p penetration by a mechanism-independent BBB leptin transporter.

  1. Nutritional status modulates behavioural and olfactory bulb Fos responses to isoamyl acetate or food odour in rats: roles of orexins and leptin.

    Science.gov (United States)

    Prud'homme, M J; Lacroix, M C; Badonnel, K; Gougis, S; Baly, C; Salesse, R; Caillol, M

    2009-09-15

    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.

  2. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells

    International Nuclear Information System (INIS)

    Meerson, Ari; Yehuda, Hila

    2016-01-01

    Obesity is a risk factor for colorectal cancer (CRC). Normal and tumor cells respond to metabolic hormones, such as leptin and insulin. Thus, obesity-associated resistance to these hormones likely leads to changes in gene expression and behavior of tumor cells. However, the mechanisms affected by leptin and insulin signaling in CRC cells remain mostly unknown. We hypothesized that microRNAs (miRNAs) are involved in the regulation of tumorigenesis-related gene expression in CRC cells by leptin and insulin. To test this hypothesis, miRNA levels in the CRC-derived cell lines HCT-116, HT-29 and DLD-1 were profiled, following leptin and insulin treatment. Candidate miRNAs were validated by RT-qPCR. Predicted miRNA targets with known roles in cancer, were validated by immunoblots and reporter assays in HCT-116 cells. Transfection of HCT-116 cells with candidate miRNA mimic was used to test in vitro effects on proliferation and invasion. Of ~800 miRNAs profiled, miR-4443 was consistently up-regulated by leptin and insulin in HCT-116 and HT-29, but not in DLD-1, which lacked normal leptin receptor expression. Dose response experiments showed that leptin at 100 ng/ml consistently up-regulated miR-4443 in HCT-116 cells, concomitantly with a significant decrease in cell invasion ability. Transfection with miR-4443 mimic decreased invasion and proliferation of HCT-116 cells. Moreover, leptin and miR-4443 transfection significantly down-regulated endogenous NCOA1 and TRAF4, both predicted targets of miR-4443 with known roles in cancer metastasis. miR-4443 was found to directly regulate TRAF4 and NCOA1, as validated by a reporter assay. The up-regulation of miR-4443 by leptin or insulin was attenuated by the inhibition of MEK1/2. Our findings suggest that miR-4443 acts in a tumor-suppressive manner by down-regulating TRAF4 and NCOA1 downstream of MEK-C/EBP-mediated leptin and insulin signaling, and that insulin and/or leptin resistance (e.g. in obesity) may suppress this pathway

  3. 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.

  4. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity.

    Science.gov (United States)

    Magno, Fernanda Cristina Carvalho Mattos; Guaraná, Helena Chrispim; Fonseca, Ana Carolina Proença; Cabello, Giselda Maria Kalil; Carneiro, João Régis Ivar; Pedrosa, Aline Pereira; Ximenes, Ana Carolina; Rosado, Eliane Lopes

    2018-01-01

    The fat mass and obesity-related ( FTO ) gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation. The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6), tumor necrosis factor α (TNFα) levels and food intake of morbidly obese women. The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m 2 . Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction. Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6 at the postprandial period. Subjects with TA showed increased postprandial IL6, and those with AA had decreased postprandial ghrelin. There was no difference in TNFα intra- and intergenotypes. The postprandial sensations of hunger were lower in AA than those with TT. There were differences between genotypes regarding ingested grams of protein by weight, cholesterol, B3, B5, B6 and B12 vitamins, and selenium potassium and sodium minerals. These findings suggest that genetics may exert an influence on physiologic factors and might alter eating behavior.

  5. Leptin Production by Encapsulated Adipocytes Increases Brown Fat, Decreases Resistin, and Improves Glucose Intolerance in Obese Mice.

    Directory of Open Access Journals (Sweden)

    David J DiSilvestro

    Full Text Available The neuroendocrine effects of leptin on metabolism hold promise to be translated into a complementary therapy to traditional insulin therapy for diabetes and obesity. However, injections of leptin can provoke inflammation. We tested the effects of leptin, produced in the physiological adipocyte location, on metabolism in mouse models of genetic and dietary obesity. We generated 3T3-L1 adipocytes constitutively secreting leptin and encapsulated them in a poly-L-lysine membrane, which protects the cells from immune rejection. Ob/ob mice (OB were injected with capsules containing no cells (empty, OB[Emp], adipocytes (OB[3T3], or adipocytes overexpressing leptin (OB[Lep] into both visceral fat depots. Leptin was found in the plasma of OB[Lep], but not OB[Emp] and OB[3T3] mice at the end of treatment (72 days. The OB[Lep] and OB[3T3] mice have transiently suppressed appetite and weight loss compared to OB[Emp]. Only OB[Lep] mice have greater brown fat mass, metabolic rate, and reduced resistin plasma levels compared to OB[Emp]. Glucose tolerance was markedly better in OB[Lep] vs. OB[Emp] and OB[3T3] mice as well as in wild type mice with high-fat diet-induced obesity and insulin resistance treated with encapsulated leptin-producing adipocytes. Our proof-of-principle study provides evidence of long-term improvement of glucose tolerance with encapsulated adipocytes producing leptin.

  6. Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

    Science.gov (United States)

    Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

    2016-09-01

    Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

  7. Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNFα levels, and food intake of women with morbid obesity

    Directory of Open Access Journals (Sweden)

    Magno FCCM

    2018-05-01

    Full Text Available Fernanda Cristina Carvalho Mattos Magno,1 Helena Chrispim Guaraná,1 Ana Carolina Proença Fonseca,2 Giselda Maria Kalil Cabello,2 João Régis Ivar Carneiro,3 Aline Pereira Pedrosa,1 Ana Carolina Ximenes,1 Eliane Lopes Rosado1 1Institute of Nutrition, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; 2Oswaldo Cruz Foundation (FIOCRUZ, Oswaldo Cruz Institute (IOC, Human Genetics Laboratory, Rio de Janeiro, RJ, Brazil; 3Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Service of Nutrology, Rio de Janeiro, RJ, Brazil Background: The fat mass and obesity-related (FTO gene has a strong relationship with obesity, extreme obesity and inflammatory state, and may also be associated with food intake regulation.Objective: The aim of the present study was to evaluate the influence of the rs9939609 single-nucleotide polymorphism of the FTO gene on appetite, ghrelin, leptin, interleukin 6 (IL6, tumor necrosis factor α (TNFα levels and food intake of morbidly obese women.Materials and methods: The study comprised 70 women, aged between 20 and 48 years, from Rio de Janeiro, Brazil. The participants were selected according to the body mass index between 40 and 60 kg/m2. Anthropometric and biochemical data were measured during fasting. Hormones and inflammatory data were measured before and after the participants ate an isocaloric meal. Dietary records were calculated and analyzed using a nutritional assessment program. Visual analog scales were used for behaviors of the sensations of appetite and food preferences. The FTO rs9939609 variant was genotyped using real-time polymerase chain reaction.Results: Participants with the AA genotype had lower values of ghrelin and IL6 and higher values of leptin than those with TT and TA in the postprandial period. Comparing the plasma concentrations of ghrelin, insulin, IL6 and TNFα intragenotypes, it was observed that those with TT had decreased leptin and increased IL6

  8. Leptin Signaling Is Required for Adaptive Changes in Food Intake, but Not Energy Expenditure, in Response to Different Thermal Conditions

    Science.gov (United States)

    Kaiyala, Karl J.; Ogimoto, Kayoko; Nelson, Jarrell T.; Schwartz, Michael W.; Morton, Gregory J.

    2015-01-01

    Survival of free-living animals depends on the ability to maintain core body temperature in the face of rapid and dramatic changes in their thermal environment. If food intake is not adjusted to meet the changing energy demands associated with changes of ambient temperature, a serious challenge to body energy stores can occur. To more fully understand the coupling of thermoregulation to energy homeostasis in normal animals and to investigate the role of the adipose hormone leptin to this process, comprehensive measures of energy homeostasis and core temperature were obtained in leptin-deficient ob/ob mice and their wild-type (WT) littermate controls when housed under cool (14°C), usual (22°C) or ∼ thermoneutral (30°C) conditions. Our findings extend previous evidence that WT mice robustly defend normothermia in response to either a lowering (14°C) or an increase (30°C) of ambient temperature without changes in body weight or body composition. In contrast, leptin-deficient, ob/ob mice fail to defend normothermia at ambient temperatures lower than thermoneutrality and exhibit marked losses of both body fat and lean mass when exposed to cooler environments (14°C). Our findings further demonstrate a strong inverse relationship between ambient temperature and energy expenditure in WT mice, a relationship that is preserved in ob/ob mice. However, thermal conductance analysis indicates defective heat retention in ob/ob mice, irrespective of temperature. While a negative relationship between ambient temperature and energy intake also exists in WT mice, this relationship is disrupted in ob/ob mice. Thus, to meet the thermoregulatory demands of different ambient temperatures, leptin signaling is required for adaptive changes in both energy intake and thermal conductance. A better understanding of the mechanisms coupling thermoregulation to energy homeostasis may lead to the development of new approaches for the treatment of obesity. PMID:25756181

  9. Leptin inhibits and ghrelin augments hypothalamic noradrenaline release after stress.

    Science.gov (United States)

    Kawakami, Akio; Okada, Nobukazu; Rokkaku, Kumiko; Honda, Kazufumi; Ishibashi, Shun; Onaka, Tatsushi

    2008-09-01

    Metabolic conditions affect hypothalamo-pituitary-adrenal responses to stressful stimuli. Here we examined effects of food deprivation, leptin and ghrelin upon noradrenaline release in the hypothalamic paraventricular nucleus (PVN) and plasma adrenocorticotropic hormone (ACTH) concentrations after stressful stimuli. Food deprivation augmented both noradrenaline release in the PVN and the increase in plasma ACTH concentration following electrical footshocks (FSs). An intracerebroventricular injection of leptin attenuated the increases in hypothalamic noradrenaline release and plasma ACTH concentrations after FSs, while ghrelin augmented these responses. These data suggest that leptin inhibits and ghrelin facilitates neuroendocrine stress responses via noradrenaline release and indicate that a decrease in leptin and an increase in ghrelin release after food deprivation might contribute to augmentation of stress-induced ACTH release in a fasting state.

  10. Circulating leptin and thyroid dysfunction

    DEFF Research Database (Denmark)

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

    2003-01-01

    and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid...

  11. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Science.gov (United States)

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

    2011-01-11

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  12. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2011-01-01

    Full Text Available Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  13. Narrative review: the role of leptin in human physiology: emerging clinical applications.

    Science.gov (United States)

    Kelesidis, Theodore; Kelesidis, Iosif; Chou, Sharon; Mantzoros, Christos S

    2010-01-19

    Leptin is a hormone secreted by adipose tissue in direct proportion to amount of body fat. The circulating leptin levels serve as a gauge of energy stores, thereby directing the regulation of energy homeostasis, neuroendocrine function, and metabolism. Persons with congenital deficiency are obese, and treatment with leptin results in dramatic weight loss through decreased food intake and possible increased energy expenditure. However, most obese persons are resistant to the weight-reducing effects of leptin. Recent studies suggest that leptin is physiologically more important as an indicator of energy deficiency, rather than energy excess, and may mediate adaptation by driving increased food intake and directing neuroendocrine function to converse energy, such as inducing hypothalamic hypogonadism to prevent fertilization. Current studies investigate the role of leptin in weight-loss management because persons who have recently lost weight have relative leptin deficiency that may drive them to regain weight. Leptin deficiency is also evident in patients with diet- or exercise-induced hypothalamic amenorrhea and lipoatrophy. Replacement of leptin in physiologic doses restores ovulatory menstruation in women with hypothalamic amenorrhea and improves metabolic dysfunction in patients with lipoatrophy, including lipoatrophy associated with HIV or highly active antiretroviral therapy. The applications of leptin continue to grow and will hopefully soon be used therapeutically.

  14. Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus

    Directory of Open Access Journals (Sweden)

    Zesemdorj Otgon-Uul

    2016-08-01

    Full Text Available Objective: The dorsomedial hypothalamus (DMH has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY, cocaine- and amphetamine-regulated transcript (CART, cholecystokinin (CCK, leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. Methods: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. Results: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN, where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. Conclusion: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. Keywords: Dorsomedial hypothalamus, GABAergic neuron, Feeding, Leptin, Glucose, Optogenetics

  15. Vinegar decreases allergenic response in lentil and egg food allergy.

    Science.gov (United States)

    Armentia, A; Dueñas-Laita, A; Pineda, F; Herrero, M; Martín, B

    2010-01-01

    Food allergy results from an atypical response of the mucosal immune system to orally consumed allergens. Antacid medication inhibits the digestion of dietary proteins and causes food allergy. A decrease of the gastric pH might enhance the function of digestion and reduce the risk of food allergy. To test a possible decrease in the allergenicity of powerful food allergens (egg, chicken, lentils) with the addition of vinegar during the cooking process. We included seven patients who suffered from anaphylaxis due to egg, chicken and lentils. We added vinegar to egg, chicken and lentil processed extracts used for skin prick tests (SPT) and compared the wheal areas obtained with the same extracts sources and the same way but without vinegar addition. Immunodetection was performed with the different processed extracts and patients' sera. Only one patient consented food challenge with vinegar-marinated-chicken. Wheal areas were significantly minor with the food extract with vinegar. Immunodetection showed a decrease of the response with vinegar processed extracts. Vinegar addition during the cooking process may decrease lentil and chicken allergenicity. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

  16. Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss

    DEFF Research Database (Denmark)

    Iepsen, E W; Lundgren, J; Dirksen, C

    2015-01-01

    of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor.......3 kg (95% CI=-0.6 to -4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=-0.6 to -1)), P....3±0.1 mmol l(-1) to the level before weight loss (-0.5mmol l(-1) (95% CI=-0.1 to -0.9)), PMeal response of peptide PYY3-36 was higher at week 52 in the GLP-1RA group compared with the control group, P

  17. Leptin Deficiency: Clinical Implications and Opportunities for Therapeutic Interventions

    OpenAIRE

    Bl?her, Susan; Shah, Sunali; Mantzoros, Christos S.

    2009-01-01

    The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and e...

  18. Leptin Intake at Physiological Doses Throughout Lactation in Male Wistar Rats Normalizes the Decreased Density of Tyrosine Hydroxylase-Immunoreactive Fibers in the Stomach Caused by Mild Gestational Calorie Restriction

    Directory of Open Access Journals (Sweden)

    Nara Szostaczuk

    2018-03-01

    Full Text Available Introduction: Gestational under nutrition in rats has been shown to decrease expression of sympathetic innervation markers in peripheral tissues of offspring, including the stomach. This has been linked to lower gastric secretion and decreased circulating levels of ghrelin. Considering the critical role of leptin intake during lactation in preventing obesity and reversing adverse developmental programming effects, we aimed to find out whether leptin supplementation may reverse the above mentioned alterations caused by mild gestational calorie restriction.Methods: Three groups of male rats were studied at a juvenile age (25 days old and during adulthood (3 and 6 months old: the offspring of ad libitum fed dams (controls, the offspring of dams that were diet restricted (20% from days 1 to 12 of gestation (CR, and CR rats supplemented with a daily oral dose of leptin (equivalent to 5 times the average amount they could receive each day from maternal milk throughout lactation (CR-Leptin. The density of TyrOH-immunoreactive (TyrOH+ fibers and the levels of Tyrosine hydroxylase (TyrOH—used as potential markers of functional sympathetic innervation—were measured in stomach. Plasma leptin and ghrelin levels were also determined.Results: Twenty five-day-old CR rats, but not CR-Leptin rats, displayed lower density of TyrOH+ fibers (−46% and TyrOH levels (−47% in stomach compared to controls. Alterations in CR animals were mitigated at 6 months of age, and differences were not significant. Adult CR-Leptin animals showed higher plasma ghrelin levels than CR animals, particularly at 3 months (+16%, and a lower leptin/ghrelin ratio (−28 and −37% at 3 and 6 months, respectively.Conclusion: Leptin intake during lactation is able to reverse the alterations in the density of TyrOH+ fibers in the stomach and normalize the increased leptin/ghrelin ratio linked to a mild gestational calorie restriction in rats, supporting the relevance of leptin as an

  19. Regulation of leptin and insulin signaling by the t cell protein tyrosine phosphatase

    OpenAIRE

    Loh, Kim Yong

    2017-01-01

    The prevalence of obesity and diabetes are increasing at alarming rates. Both are major health concerns worldwide. Food intake, energy expenditure and hepatic glucose production are regulated by hypothalamic neuronal circuits that respond to peripheral signals including leptin and insulin. Leptin is produced by adipose tissue and acts in the hypothalamus via the JAK2/STAT3 signaling pathway to decrease food intake and increase energy expenditure. It is now also widely appreciated that insulin...

  20. Ceruletide decreases food intake in non-obese man.

    Science.gov (United States)

    Stacher, G; Steinringer, H; Schmierer, G; Schneider, C; Winklehner, S

    1982-01-01

    Cholecystokinin decreases food intake in animals and in man. This study investigated whether the structurally related ceruletide reduces food intake in healthy non-obese man. Twelve females and 12 males participated, after an over-night fast, in each of two experiments. During the basal 40 min, saline was infused IV. Thereafter, the infusion was, in random double blind fashion, either continued with saline or switched to 60 or 120 ng/kg b. wt/hr ceruletide. Butter was melted in a pan and scrambled eggs with ham were prepared in front of the subjects, who were instructed to eat, together with bread and mallow tea, as much as they wanted. With 120 ng/kg/hr ceruletide, the subjects ate significantly less (16.8 percent) than with saline (3725 kJ +/- 489 SEM and 4340 kJ +/- 536, respectively; p less than 0.025). They also reported less hunger (p less than 0.005) and activation (p less than 0.005) and activation (p less than 0.01), and had longer reaction times (p less than 0.01) and a weaker psychomotor performance (p less than 0.025). 60 ng/kg/hr ceruletide decreased food intake only slightly (6.6%; 3089 kJ +/- 253 and 3292 kJ +/- 300 respectively) and no significant changes in the above measures occurred. In conclusion, ceruletide reduces food intake in man, thus resembling the effects of cholecystokinin.

  1. 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.

  2. Relationship between peripheral leptin receptor and leptin in obese subjects

    International Nuclear Information System (INIS)

    Sun Junjiang; Du Tongxin; Wang Zizheng; Wang Shukui; Huang Min

    2002-01-01

    Objective: To investigate the relationship between leptin resistance and leptin receptor in obese subjects. Methods: Forty-four individuals undergoing surgery, exclusive of diabetic mellitus, chronic inflammatory and malignant diseases, were divided into 3 groups according to the body mass index (BMI), normal controls (n=15), weight excess (n=14), and obesity group (n=15). Fasting serum leptin were detected via ELISA kits, leptin receptor (Bmax) in peripheral adipose tissues was detected by radioligand assay. Results: Serum leptin levels were higher significantly in weight excess and obesity cases groups (10.3±4.45 and 13.2±3.26 vs 5.51±3.23 μg/L, both P<0.05, respectively) compared with normal control group, suggesting the existence of leptin resistance, while the leptin receptor of the weight excess and obese groups decreased significantly than that of normal control group (36.9 ± 5.89 and 24.3 ± 3.95 vs 76.5 ± 35.3 fmol/mg protein, both P<0.01, respectively), there was no statistical differences for Kd value among three groups. Also, there was a negative correlation between BMI and leptin receptor (r=-0.613, P<0.05), and no significant correlation was found between serum leptin and peripheral leptin receptor. Conclusion: The result suggested that there was expression of leptin receptor in peripheral adipose tissues and low level of leptin receptor expression may contribute to the development of leptin resistance and obesity

  3. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Directory of Open Access Journals (Sweden)

    Travis McMurphy

    Full Text Available Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  4. The anti-tumor activity of a neutralizing nanobody targeting leptin receptor in a mouse model of melanoma.

    Science.gov (United States)

    McMurphy, Travis; Xiao, Run; Magee, Daniel; Slater, Andrew; Zabeau, Lennart; Tavernier, Jan; Cao, Lei

    2014-01-01

    Environmental and genetic activation of a brain-adipocyte axis inhibits cancer progression. Leptin is the primary peripheral mediator of this anticancer effect in a mouse model of melanoma. In this study we assessed the effect of a leptin receptor antagonist on melanoma progression. Local administration of a neutralizing nanobody targeting the leptin receptor at low dose adjacent to tumor decreased tumor mass with no effects on body weight or food intake. In contrast, systemic administration of the nanobody failed to suppress tumor growth. Daily intraperitoneal injection of high-dose nanobody led to weight gain, hyperphagia, increased adiposity, hyperleptinemia, and hyperinsulinemia, and central effects mimicking leptin deficiency. The blockade of central actions of leptin by systemic delivery of nanobody may compromise its anticancer effect, underscoring the need to develop peripherally acting leptin antagonists coupled with efficient cancer-targeting delivery.

  5. 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.

  6. 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 ...

  7. LEPTIN RESISTANCE AND TYPE 2 DIABETES

    Directory of Open Access Journals (Sweden)

    O. M. Oleshchuk

    2017-07-01

    Full Text Available Leptin is one of adipocyte-secreted hormones. It signals to the brain and other tissues about the status of body energy reserves. Circulating leptin levels are directly proportional to the amount of the body fat. Leptin concentration increases when surfeit and decreases during fasting. Obese patients are hyperleptinemic compared with thin persons and they are tolerant to the central hypothalamic effects of leptin. The reduced sensitivity toward exogenous and endogenous leptin is commonly referred to as leptin resistance. Alterations in the signaling of the long isoform of the leptin receptor play the crucial role in leptin resistance. Surfeit may induce leptin resistance and other metabolic sequelae of obesity. Leptin insensitivity and insulin resistance play a major role in the development of type 2 diabetes. Metformin remains the preferred first-line pharmacologic agent for the treatment of type 2 diabetes. It reduces hepatic glucose production, increases glucose uptake in peripheral tissue and can lead to weight loss. Metformin decreases both insulin and leptin concentration, restores the sensitivity to these hormones. But some studies have shown poor relationship between metformin action and leptin level. And the mechanism of metformin action on leptin resistance remains unclear. Thus, these issues should be studied as well as polymorphisms in genes encoding metformin action.

  8. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Cai, Zhengwei; Lin, Shuying; Dubinion, John H; Hall, John E

    2011-05-01

    Although the central nervous system melanocortin system is an important regulator of energy balance, the role of proopiomelanocortin (POMC) neurons in mediating the chronic effects of leptin on appetite, blood pressure, and glucose regulation is unknown. Using Cre/loxP technology we tested whether leptin receptor deletion in POMC neurons (LepR(flox/flox)/POMC-Cre mice) attenuates the chronic effects of leptin to increase mean arterial pressure (MAP), enhance glucose use and oxygen consumption, and reduce appetite. LepR(flox/flox)/POMC-Cre, wild-type, LepR(flox/flox), and POMC-Cre mice were instrumented for MAP and heart rate measurement by telemetry and venous catheters for infusions. LepR(flox/flox)/POMC-Cre mice were heavier, hyperglycemic, hyperinsulinemic, and hyperleptinemic compared with wild-type, LepR(flox/flox), and POMC-Cre mice. Despite exhibiting features of metabolic syndrome, LepR(flox/flox)/POMC-Cre mice had normal MAP and heart rate compared with LepR(flox/flox) but lower MAP and heart rate compared with wild-type mice. After a 5-day control period, leptin was infused (2 μg/kg per minute, IV) for 7 days. In control mice, leptin increased MAP by ≈5 mm Hg despite decreasing food intake by ≈35%. In contrast, leptin infusion in LepR(flox/flox)/POMC-Cre mice reduced MAP by ≈3 mm Hg and food intake by ≈28%. Leptin significantly decreased insulin and glucose levels in control mice but not in LepR(flox/flox)/POMC-Cre mice. Leptin increased oxygen consumption in LepR(flox/flox)/POMC-Cre and wild-type mice. Activation of POMC neurons is necessary for the chronic effects of leptin to raise MAP and reduce insulin and glucose levels, whereas leptin receptors in other areas of the brain other than POMC neurons appear to play a key role in mediating the chronic effects of leptin on appetite and oxygen consumption.

  9. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells.

    Science.gov (United States)

    Kievit, Paul; Howard, Jane K; Badman, Michael K; Balthasar, Nina; Coppari, Roberto; Mori, Hiroyuki; Lee, Charlotte E; Elmquist, Joel K; Yoshimura, Akihiko; Flier, Jeffrey S

    2006-08-01

    Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.

  10. Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Fontes-Villalba, Maelán; Lindeberg, Staffan; Granfeldt, Yvonne

    2016-01-01

    Background: We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2...... diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods: In a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned...

  11. Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice.

    Science.gov (United States)

    Mercer, Aaron J; Stuart, Ronald C; Attard, Courtney A; Otero-Corchon, Veronica; Nillni, Eduardo A; Low, Malcolm J

    2014-04-15

    Hypothalamic proopiomelanocortin (POMC) neurons constitute a critical anorexigenic node in the central nervous system (CNS) for maintaining energy balance. These neurons directly affect energy expenditure and feeding behavior by releasing bioactive neuropeptides but are also subject to signals directly related to nutritional state such as the adipokine leptin. To further investigate the interaction of diet and leptin on hypothalamic POMC peptide levels, we exposed 8- to 10-wk-old male POMC-Discosoma red fluorescent protein (DsRed) transgenic reporter mice to either 24-48 h (acute) or 2 wk (chronic) food restriction, high-fat diet (HFD), or leptin treatment. Using semiquantitative immunofluorescence and radioimmunoassays, we discovered that acute fasting and chronic food restriction decreased the levels of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and β-endorphin in the hypothalamus, together with decreased DsRed fluorescence, compared with control ad libitum-fed mice. Furthermore, acute but not chronic HFD or leptin administration selectively increased α-MSH levels in POMC fibers and increased DsRed fluorescence in POMC cell bodies. HFD and leptin treatments comparably increased circulating leptin levels at both time points, suggesting that transcription of Pomc and synthesis of POMC peptide products are not modified in direct relation to the concentration of plasma leptin. Our findings indicate that negative energy balance persistently downregulated POMC peptide levels, and this phenomenon may be partially explained by decreased leptin levels, since these changes were blocked in fasted mice treated with leptin. In contrast, sustained elevation of plasma leptin by HFD or hormone supplementation did not significantly alter POMC peptide levels, indicating that enhanced leptin signaling does not chronically increase Pomc transcription and peptide synthesis.

  12. Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

    Science.gov (United States)

    Herisson, F M; Waas, J R; Fredriksson, R; Schiöth, H B; Levine, A S; Olszewski, P K

    2016-04-01

    Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting. © 2016

  13. Estradiol, SHBG and leptin interplay with food craving and intake across the menstrual cycle

    Science.gov (United States)

    Objective: To understand the association between ovarian hormones, non-acute satiety hormones and craving calorie dense foods in the luteal phase. Methods: 17 premenopausal women, mean age 23.2 y, mean BMI 22.4 kg/m2 with regular menstrual cycles were studied during late follicular (FP) and luteal ...

  14. 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.

  15. Leptin deficiency: clinical implications and opportunities for therapeutic interventions.

    Science.gov (United States)

    Blüher, Susan; Shah, Sunali; Mantzoros, Christos S

    2009-10-01

    The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. Geranylgeranylacetone prevents stress-induced decline of leptin secretion in mice.

    Science.gov (United States)

    Itai, Miki; Kuwano, Yuki; Nishikawa, Tatsuya; Rokutan, Kazuhito; Kensei, Nishida

    2018-01-01

    Geranylgeranylacetone (GGA) is a chaperon inducer that protects various types of cell and tissue against stress. We examined whether GGA modulated energy intake and expenditure under stressful conditions. After mice were untreated or treated orally with GGA (0.16 g per kg body weight per day) for 10 days, they were subjected to 2-h restraint stress once or once a day for 5 consecutive days. GGA administration did not affect corticosterone response to the stress. Restraint stress rapidly decreased plasma leptin levels in control mice. GGA significantly increased circulating leptin levels without changing food intake and prevented the stress-induced decline of circulating leptin. However GGA-treated mice significantly reduced food intake during the repeated stress, compared with control mice. GGA prevented the stress-induced decline of leptin mRNA and its protein levels in epidydimal adipose tissues. We also found that GGA decreased ghrelin mRNA expression in gastric mucosa before the stress, whereas GGA-treated mice recovered the ghrelin mRNA expression to the baseline level after the repeated stress. Leptin and ghrelin are now recognized as regulators of anxiety and depressive mood. Our results suggest that GGA may regulate food intake and relief stress-induced mood disturbance through regulating leptin and ghrelin secretions. J. Med. Invest. 65:103-109, February, 2018.

  18. Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

    Science.gov (United States)

    Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

    2017-02-01

    The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

  19. 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

  20. Leptin in humans: lessons from translational research.

    Science.gov (United States)

    Blüher, Susann; Mantzoros, Christos S

    2009-03-01

    Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects with complete (congenital) leptin deficiency caused by mutations in the leptin gene as well as in humans with relative leptin deficiency, including states of lipoatrophy or negative energy balance and neuroendocrine dysfunction, as for instance seen with hypothalamic amenorrhea in states of exercise-induced weight loss. In those conditions, most neuroendocrine, metabolic, or immune disturbances can be restored by leptin administration. Leptin replacement therapy is thus a promising approach in several disease states, including congenital complete leptin deficiency, states of energy deprivation, including anorexia nervosa or milder forms of hypothalamic amenorrhea, as well as syndromes of insulin resistance seen in conditions such as congenital or acquired lipodystrophy. In contrast, states of energy excess such as garden-variety obesity are associated with hyperleptinemia that reflects either leptin tolerance or leptin resistance. For those conditions, development of leptin sensitizers is currently a focus of pharmaceutical research. This article summarizes our current understanding of leptin's role in human physiology and its potential role as a novel therapeutic option in human disease states associated with a new hormone deficiency, ie, leptin deficiency.

  1. A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins 4 and 5 while Decreasing Food Intake in the Normal Wistar Rat*

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M. Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L.

    2010-01-01

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD+]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain l-glutamate by 15–20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain. PMID:20529850

  2. A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

    Science.gov (United States)

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L

    2010-08-20

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

  3. Leptin Suppresses the Rewarding Effects of Running via STAT3 Signaling in Dopamine Neurons.

    Science.gov (United States)

    Fernandes, Maria Fernanda A; Matthys, Dominique; Hryhorczuk, Cécile; Sharma, Sandeep; Mogra, Shabana; Alquier, Thierry; Fulton, Stephanie

    2015-10-06

    The adipose hormone leptin potently influences physical activity. Leptin can decrease locomotion and running, yet the mechanisms involved and the influence of leptin on the rewarding effects of running ("runner's high") are unknown. Leptin receptor (LepR) signaling involves activation of signal transducer and activator of transcription-3 (STAT3), including in dopamine neurons of the ventral tegmental area (VTA) that are essential for reward-relevant behavior. We found that mice lacking STAT3 in dopamine neurons exhibit greater voluntary running, an effect reversed by viral-mediated STAT3 restoration. STAT3 deletion increased the rewarding effects of running whereas intra-VTA leptin blocked it in a STAT3-dependent manner. Finally, STAT3 loss-of-function reduced mesolimbic dopamine overflow and function. Findings suggest that leptin influences the motivational effects of running via LepR-STAT3 modulation of dopamine tone. Falling leptin is hypothesized to increase stamina and the rewarding effects of running as an adaptive means to enhance the pursuit and procurement of food. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Presence and distribution of leptin and leptin receptor in the canine gallbladder.

    Science.gov (United States)

    Lee, Sungin; Lee, Aeri; Kweon, Oh-Kyeong; Kim, Wan Hee

    2016-09-01

    The hormone leptin is produced by mature adipocytes and plays an important role in regulating food intake and energy metabolism through its interaction with the leptin receptor. In addition to roles in obesity and obesity-related diseases, leptin has been reported to affect the components and secretion of bile in leptin-deficient mice. Furthermore, gallbladder diseases such as cholelithiasis are known to be associated with serum leptin concentrations in humans. We hypothesized that the canine gallbladder is a source of leptin and that the leptin receptor may be localized in the gallbladder, where it plays a role in regulating the function of this organ. The aim of this study was to demonstrate the presence and expression patterns of leptin and its receptors in normal canine gallbladders using reverse transcriptase-PCR (RT-PCR) and immunohistochemistry. Clinically normal gallbladder tissue samples were obtained from four healthy beagle dogs with similar body condition scores. RT-PCR and sequencing of the amplified PCR products revealed the presence of leptin mRNA and its receptors in the gallbladder. Immunohistochemical investigations demonstrated the expression of leptin and its receptors in the luminal single columnar and tubuloalveolar glandular epithelial cells. In conclusion, the results of this study demonstrated the presence of leptin and its receptors in the gallbladders of dogs. Leptin and its receptor were both localized throughout the cytoplasm of luminal and glandular epithelial cells. These results suggested that the gallbladder is not only a source of leptin, but also a target of leptin though autocrine/paracrine mechanisms. The results of this study could increase the understanding of both the normal physiological functions of the gallbladder and the pathophysiological mechanisms of gallbladder diseases characterized by leptin system dysfunction. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  5. Decrease of Pseudomonas aeruginosa biofilm formation by food waste materials

    Czech Academy of Sciences Publication Activity Database

    Maděrová, Z.; Horská, K.; Kim, S.-R.; Lee, Ch.-H.; Pospíšková, K.; Šafaříková, Miroslava; Šafařík, Ivo

    2016-01-01

    Roč. 73, č. 9 (2016), s. 2143-2149 ISSN 0273-1223 Institutional support: RVO:60077344 Keywords : biofilm * food waste materials * magnetic spent grain * Pseudomonas aeruginosa Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.197, year: 2016

  6. Leptin level in plasma of lactating buffaloes fed two diets with different energy and protein concentrations

    Directory of Open Access Journals (Sweden)

    A. Parmeggiani

    2011-03-01

    Full Text Available Leptin, a protein mainly secreted from the white adipocytes, has been shown to contribute to the regulation of energy metabolism, feeding behaviour and whole body energy balance. Moreover, leptin gene activity and leptin secretion are correlated with body adiposity and changes in food intake. Furthermore, leptin could also modulate endocrine response to changes in nutritional status and/or tissue sensitivity to hormones (Houseknecht et al., 1998; Romsos, 1998. Several factors are known to influence plasma leptin in rodents and humans: particularly it increases by body fatness, insulin, glucocorticoids, estrogens and decreases by food deprivation (Saladin et al., 1995; Ahima et al., 1996; Shimizu et al., 1997. These ones and several other observations have led to the hypothesis that leptin is a signal arising from adipose tissue, linked to the level of fat reserves and/or the nutritional status. This signal directly influences the central nervous system and peripheral organs, resulting in a better adaptation of body metabolism and physiological functions to the availability of metabolic energy...........

  7. Twentieth Anniversary of Leptin discovery and the Approval of Myalept by FDA

    Directory of Open Access Journals (Sweden)

    Ata Mahmoodpoor

    2015-04-01

    Full Text Available Leptin is a 16 kDa hormone that is mainly expressed in adipose tissues (1. The major target of leptin is hypothalamus and it suppresses food intake and energy consumption, consequently diminishing adipose deposits and body weight (2, 3. The OB gene was isolated by Friedman in 1994 (4.  Based on the suggestion of Roger Guillemin, Friedman named this new hormone "leptin" from the Greek lepto meaning thin (5, 6. Since leptin discovery, numerous studies have been conducted on its physiological effects and its function in pathological conditions. Most of studies on leptin concentrated on its metabolic actions (7, receptors (8 and further broad functions such as immunity modulation (9 and memory processing (10. Considering such a vast range of functions, it is clear that patients with lack of leptin physiologically need pharmacological interventions. At this moment, we are in the twentieth year of leptin discovery. Finally, FDA approved a drug named Myalept (metreleptin for injection on February 2014 to treat rare metabolic disease caused by leptin deficiency. Congenital generalized lipodystrophy is a disorder with partial lack of fat tissues (11. The trial for the safety and effectiveness of Myalept demonstrated decrease in HbA1c, fasting blood glucose, and triglycerides (11. Nevertheless, there are some limitations to the usage of Myalept in HIV-related lipodystrophy and some metabolic disorders (11. Moreover, it may increase the risk of lymphoma by producing anti-metreleptin antibodies neutralizing endogenous leptin. Considering these concerns, Myalept is available only through a limited profile under a Risk Evaluation and Mitigation Strategy (REMS. Myalept is contraindicated in patients with general obesity not related to congenital leptin deficiency (12. Even though, Myalept has very limited indications for use in general population, it is considered a milestone towards the discovery of novel treatments for Leptin deficiencies and disorders

  8. Chronic blood pressure and appetite responses to central leptin infusion in rats fed a high fat diet.

    Science.gov (United States)

    Dubinion, John H; da Silva, Alexandre A; Hall, John E

    2011-04-01

    Obesity has been suggested to induce selective leptin resistance whereby leptin's anorexic effects are attenuated, whereas the effects to increase sympathetic nervous system activity and blood pressure remain intact. Most studies, however, have tested only the acute responses to leptin administration. This study tested whether feeding a high-fat diet causes resistance to the appetite and cardiovascular responses to chronic central leptin infusion. Sprague-Dawley rats were fed high-fat diet (40% kcal from fat, n=5) or normal-fat diet (13% kcal from fat, n=5) for a year. Radiotelemeters were implanted for continuous monitoring of mean arterial pressure (MAP) and heart rate (HR). A 21G steel cannula was implanted in the lateral cerebral ventricle [intracerebroventricular (ICV)]. After recovery, leptin was infused ICV at 0.02 μg/kg per min for 10 days. High-fat rats were heavier than normal-fat rats (582±12 vs. 511±19 g) and exhibited significantly higher MAP (114±3 vs. 96±7 mmHg). Although the acute (24 h) effects of leptin were attenuated in high-fat rats, chronic ICV leptin infusion decreased caloric intake in both groups similarly (50±8 vs. 40±10%) by day 5. Despite decreased food intake and weight loss, leptin infusion significantly increased MAP and HR in both high-fat and normal-fat rats (7±2 and 5±1 mmHg; 18±11 and 21±10 b.p.m., respectively). These results suggest that obesity induced by feeding a high-fat diet blunts the acute anorexic effects of leptin but does not cause significant resistance to the chronic central nervous system effects of leptin on appetite, MAP, or HR.

  9. Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; D'Angiulli, Amedeo; Rodríguez-Díaz, Joel; Blaurock-Busch, Eleonore; Busch, Yvette; Chao, Chih-kai; Thompson, Charles; Mukherjee, Partha S; Torres-Jardón, Ricardo; Perry, George

    2015-07-01

    Millions of Mexico, US and across the world children are overweight and obese. Exposure to fossil-fuel combustion sources increases the risk for obesity and diabetes, while long-term exposure to fine particulate matter (PM2.5) and ozone (O3) above US EPA standards is associated with increased risk of Alzheimer's disease (AD). Mexico City Metropolitan Area children are chronically exposed to PM2.5 and O3 concentrations above the standards and exhibit systemic, brain and intrathecal inflammation, cognitive deficits, and Alzheimer disease neuropathology. We investigated adipokines, food reward hormones, endothelial dysfunction, vitamin D and apolipoprotein E (APOE) relationships in 80 healthy, normal weight 11.1±3.2 year olds matched by age, gender, BMI and SES, low (n: 26) versus high (n:54) PM2.5 exposures. Mexico City children had higher leptin and endothelin-1 (pMexico City APOE 4 versus 3 children had higher glucose (p=0.009). Serum 25-hydroxyvitamin DMexico City children. Leptin is strongly positively associated to PM 2.5 cumulative exposures. Residing in a high PM2.5 and O3 environment is associated with 12h fasting hyperleptinemia, altered appetite-regulating peptides, vitamin D deficiency, and increases in ET-1 in clinically healthy children. These changes could signal the future trajectory of urban children towards the development of insulin resistance, obesity, type II diabetes, premature cardiovascular disease, addiction-like behavior, cognitive impairment and Alzheimer's disease. Increased efforts should be made to decrease pediatric PM2.5 exposures, to deliver health interventions prior to the development of obesity and to identify and mitigate environmental factors influencing obesity and Alzheimer disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus)

    OpenAIRE

    Huixian Zhang; Geng Qin; Yanhong Zhang; Shuisheng Li; Qiang Lin

    2016-01-01

    ABSTRACT 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. Alth...

  11. 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.

  12. Cross-talk between estrogen and leptin signaling in the hypothalamus.

    Science.gov (United States)

    Gao, Qian; Horvath, Tamas L

    2008-05-01

    Obesity, characterized by enhanced food intake (hyperphagia) and reduced energy expenditure that results in the accumulation of body fat, is a major risk factor for various diseases, including diabetes, cardiovascular disease, and cancer. In the United States, more than half of adults are overweight, and this number continues to increase. The adipocyte-secreted hormone leptin and its downstream signaling mediators play crucial roles in the regulation of energy balance. Leptin decreases feeding while increasing energy expenditure and permitting energy-intensive neuroendocrine processes, such as reproduction. Thus, leptin also modulates the neuroendocrine reproductive axis. The gonadal steroid hormone estrogen plays a central role in the regulation of reproduction and also contributes to the regulation of energy balance. Estrogen deficiency promotes feeding and weight gain, and estrogen facilitates, and to some extent mimics, some actions of leptin. In this review, we examine the functions of estrogen and leptin in the brain, with a focus on mechanisms by which leptin and estrogen cooperate in the regulation of energy homeostasis.

  13. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2012-01-01

    Full Text Available The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed.

  14. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Science.gov (United States)

    Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

    2012-01-01

    The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

  15. 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

  16. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  17. Leptin is an effective treatment for hypothalamic amenorrhea.

    Science.gov (United States)

    Chou, Sharon H; Chamberland, John P; Liu, Xiaowen; Matarese, Giuseppe; Gao, Chuanyun; Stefanakis, Rianna; Brinkoetter, Mary T; Gong, Huizhi; Arampatzi, Kalliopi; Mantzoros, Christos S

    2011-04-19

    Hypothalamic amenorrhea (HA) is associated with dysfunction of the hypothalamic-pituitary-peripheral endocrine axes, leading to infertility and bone loss, and usually is caused by chronic energy deficiency secondary to strenuous exercise and/or decreased food intake. Energy deficiency also leads to hypoleptinemia, which has been proposed, on the basis of observational studies as well as an open-label study, to mediate the neuroendocrine abnormalities associated with this condition. To prove definitively a causal role of leptin in the pathogenesis of HA, we performed a randomized, double-blinded, placebo-controlled trial of human recombinant leptin (metreleptin) in replacement doses over 36 wk in women with HA. We assessed its effects on reproductive outcomes, neuroendocrine function, and bone metabolism. Leptin replacement resulted in recovery of menstruation and corrected the abnormalities in the gonadal, thyroid, growth hormone, and adrenal axes. We also demonstrated changes in markers of bone metabolism suggestive of bone formation, but no changes in bone mineral density were detected over the short duration of this study. If these data are confirmed, metreleptin administration in replacement doses to normalize circulating leptin levels may prove to be a safe and effective therapy for women with HA.

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

    Science.gov (United States)

    Rizk, Nasser M.; Sharif, Elham

    2015-01-01

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

  19. 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.

  20. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet.

    Science.gov (United States)

    Mars, M; de Graaf, C; de Groot, C P G M; van Rossum, C T M; Kok, F J

    2006-01-01

    Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. A total of 44 healthy adult men (aged: 43 +/- 5 years; BMI: 27.3 +/- 3.2 kg/m(2)). Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat (r = -0.39; P < 0.05) and total appetite (r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r = -0.15, P = 0.32; day 2 r = -0.31, P =< 0.05; day 4 r = -0.41, P < 0.01). The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite.

  1. Role of leptin resistance in the development of obesity in older patients

    Directory of Open Access Journals (Sweden)

    Carter S

    2013-07-01

    Full Text Available Sophie Carter,1,* Alexandre Caron,2,* Denis Richard,2 Frédéric Picard1 1Faculty of Pharmacy, 2Faculty of Medicine, Dept Anatomy and Physiology, Université Laval, Québec, QC, Canada *These authors contributed equally to the work Abstract: Obesity is a global epidemic associated with aging-like cellular processes; in both aging and obesity, resistance to hormones such as insulin and leptin can be observed. Leptin is a circulating hormone/cytokine with central and peripheral effects that is released mainly by subcutaneous white adipose tissue. Centrally, leptin controls food intake, energy expenditure, and fat distribution, whereas it controls (among several others insulin sensitivity, free fatty acids (FFAs oxidation, and lipolysis in the periphery. Aging is associated with important changes in both the distribution and the composition of adipose tissue. Fat is redistributed from the subcutaneous to the visceral depot and increased inflammation participates in adipocyte dysfunction. This redistribution of adipose tissue in favor of visceral fat influences negatively both longevity and healthy aging as shown in numerous animal models. These modifications observed during aging are also associated with leptin resistance. This resistance blunts normal central and peripheral functions of leptin, which leads to a decrease in neuroendocrine function and insulin sensitivity, an imbalance in energy regulation, and disturbances in lipid metabolism. Here, we review how age-related leptin resistance triggers metabolic disturbances and affects the longevity of obese patients. Furthermore, we discuss the potential impacts of leptin resistance on the decline of brown adipose tissue thermogenesis observed in elderly individuals. Keywords: leptin, obesity, aging, insulin sensitivity, brown adipose tissue

  2. Plasma leptin and growth hormone levels in the fine flounder (Paralichthys adspersus) increase gradually during fasting and decline rapidly after refeeding.

    Science.gov (United States)

    Fuentes, Eduardo N; Kling, Peter; Einarsdottir, Ingibjörg Eir; Alvarez, Marco; Valdés, Juan Antonio; Molina, Alfredo; Björnsson, Björn Thrandur

    2012-05-15

    In fish, recent studies have indicated an anorexigenic role of leptin and thus its possible involvement in regulation of energy balance and growth. In the present study, the effects of fasting and refeeding periods on plasma leptin levels were studied in the fine flounder, a flatfish with remarkably slow growth. To further assess the endocrine status of the fish during periods of catabolism and anabolism, plasma growth hormone (GH) levels were also analyzed. Under normal feeding condition, plasma leptin and GH levels remained stable and relatively high in comparison with other teleost species. For the three separate groups of fish, fasted for 2, 3, and 4 weeks, respectively, plasma leptin levels increase gradually, becoming significantly elevated after 3 weeks, and reaching highest levels after 4-week fasting. Plasma GH levels were significantly elevated after 2-week fasting. At the onset of refeeding, following a single meal, leptin levels decline rapidly to lower than initial levels within 2 h, irrespective of the length of fasting. Plasma GH also decline, the decrease being significant after 4, 24 and 2 h for the 2, 3 and 4-week fasted groups, respectively. This study shows that plasma leptin levels in the fine flounder are strongly linked to nutritional status and suggests that leptin secretion is regulated by fast-acting mechanisms. Elevated leptin levels in fasted fish may contribute to a passive survival strategy of species which experience natural food shortage periods by lowering appetite and limiting physical foraging activity. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. 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

  4. Blue lighting decreases the amount of food consumed in men, but not in women.

    Science.gov (United States)

    Cho, Sungeun; Han, Ashley; Taylor, Michael H; Huck, Alexandria C; Mishler, Amanda M; Mattal, Kyle L; Barker, Caleb A; Seo, Han-Seok

    2015-02-01

    Previous research has demonstrated that colors of lighting can modulate participants' motivation to consume the food placed under the lighting. This study was designed to determine whether the colors of lighting can affect the amount of food consumed, in addition to sensory perception of the food. The influence of lighting color was also compared between men and women. One-hundred twelve participants (62 men and 50 women) were asked to consume a breakfast meal (omelets and mini-pancakes) under one of three different lighting colors: white, yellow, and blue. During the test, hedonic impression of the food's appearance, willingness to eat, overall flavor intensity and overall impression of the food, and meal size (i.e., the amount of food consumed) were measured. Blue lighting decreased the hedonic impression of the food's appearance, but not the willingness to eat, compared to yellow and white lighting conditions. The blue lighting significantly decreased the amount consumed in men, but not in women, compared to yellow and white lighting conditions. Overall flavor intensity and overall impression of the food were not significantly different among the three lighting colors. In conclusion, this study provides empirical evidence that the color of lighting can modulate the meal size. In particular, blue lighting can decrease the amount of food eaten in men without reducing their acceptability of the food. Published by Elsevier Ltd.

  5. 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...

  6. Glucagon-like peptide 1 interacts with ghrelin and leptin to regulate glucose metabolism and food intake through vagal afferent neuron signaling.

    Science.gov (United States)

    Ronveaux, Charlotte C; Tomé, Daniel; Raybould, Helen E

    2015-04-01

    Emerging evidence has suggested a possible physiologic role for peripheral glucagon-like peptide 1 (GLP-1) in regulating glucose metabolism and food intake. The likely site of action of GLP-1 is on vagal afferent neurons (VANs). The vagal afferent pathway is the major neural pathway by which information about ingested nutrients reaches the central nervous system and influences feeding behavior. Peripheral GLP-1 acts on VANs to inhibit food intake. The mechanism of the GLP-1 receptor (GLP-1R) is unlike other gut-derived receptors; GLP-1Rs change their cellular localization according to feeding status rather than their protein concentrations. It is possible that several gut peptides are involved in mediating GLP-1R translocation. The mechanism of peripheral GLP-1R translocation still needs to be elucidated. We review data supporting the role of peripheral GLP-1 acting on VANs in influencing glucose homeostasis and feeding behavior. We highlight evidence demonstrating that GLP-1 interacts with ghrelin and leptin to induce satiation. Our aim was to understand the mechanism of peripheral GLP-1 in the development of noninvasive antiobesity treatments. © 2015 American Society for Nutrition.

  7. Leptin and bone mineral density

    DEFF Research Database (Denmark)

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

    2003-01-01

    Leptin has been suggested to decrease bone mineral density (BMD). This observational analysis explored the relationship between serum leptin and BMD in 327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/- 6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg...... males, but it also stresses the fact that the strong covariation between the examined variables is a shortcoming of the cross-sectional design....

  8. 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....

  9. Adipocyte Versus Pituitary Leptin in the Regulation of Pituitary Hormones: Somatotropes Develop Normally in the Absence of Circulating Leptin

    Science.gov (United States)

    Odle, Angela K.; Haney, Anessa; Allensworth-James, Melody; Akhter, Noor

    2014-01-01

    Leptin is a cytokine produced by white fat cells, skeletal muscle, the placenta, and the pituitary gland among other tissues. Best known for its role in regulating appetite and energy expenditure, leptin is produced largely by and in proportion to white fat cells. Leptin is also important to the maintenance and function of the GH cells of the pituitary. This was shown when the deletion of leptin receptors on somatotropes caused decreased numbers of GH cells, decreased circulating GH, and adult-onset obesity. To determine the source of leptin most vital to GH cells and other pituitary cell types, we compared two different leptin knockout models with Cre-lox technology. The global Lep-null model is like the ob/ob mouse, whereby only the entire exon 3 is deleted. The selective adipocyte-Lep-null model lacks adipocyte leptin but retains pituitary leptin, allowing us to investigate the pituitary as a potential source of circulating leptin. Male and female mice lacking adipocyte leptin (Adipocyte-lep-null) did not produce any detectable circulating leptin and were infertile, suggesting that the pituitary does not contribute to serum levels. In the presence of only pituitary leptin, however, these same mutants were able to maintain somatotrope numbers and GH mRNA levels. Serum GH trended low, but values were not significant. However, hypothalamic GHRH mRNA was significantly reduced in these animals. Other serum hormone and pituitary mRNA differences were observed, some of which varied from previous results reported in ob/ob animals. Whereas pituitary leptin is capable of maintaining somatotrope numbers and GH mRNA production, the decreased hypothalamic GHRH mRNA and low (but not significant) serum GH levels indicate an important role for adipocyte leptin in the regulation of GH secretion in the mouse. Thus, normal GH secretion may require the coordinated actions of both adipocyte and pituitary leptin. PMID:25116704

  10. 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.

  11. Leptin and Leptin Resistance in the Pathogenesis of Obstructive Sleep Apnea: A Possible Link to Oxidative Stress and Cardiovascular Complications

    Directory of Open Access Journals (Sweden)

    Slava Berger

    2018-01-01

    Full Text Available Obesity-related sleep breathing disorders such as obstructive sleep apnea (OSA and obesity hypoventilation syndrome (OHS cause intermittent hypoxia (IH during sleep, a powerful trigger of oxidative stress. Obesity also leads to dramatic increases in circulating levels of leptin, a hormone produced in adipose tissue. Leptin acts in the hypothalamus to suppress food intake and increase metabolic rate. However, obese individuals are resistant to metabolic effects of leptin. Leptin also activates the sympathetic nervous system without any evidence of resistance, possibly because these effects occur peripherally without a need to penetrate the blood-brain barrier. IH is a potent stimulator of leptin expression and release from adipose tissue. Hyperleptinemia and leptin resistance may upregulate generation of reactive oxygen species, increasing oxidative stress and promoting inflammation. The current review summarizes recent data on a possible link between leptin and oxidative stress in the pathogenesis of sleep breathing disorders.

  12. Voluntary exercise improves high-fat diet-induced leptin resistance independent of adiposity.

    Science.gov (United States)

    Krawczewski Carhuatanta, Kimberly A; Demuro, Giovanna; Tschöp, Matthias H; Pfluger, Paul T; Benoit, Stephen C; Obici, Silvana

    2011-07-01

    The efficacy of exercise as primary prevention of obesity is the subject of intense investigation. Here, we show that voluntary exercise in a mouse strain susceptible to diet-induced obesity (C57B6J) decreases fat mass and increases energy expenditure. In addition, exercise attenuates obesity in mice fed a high-fat diet (HFD). Using FosB immunoreactivity as a marker of chronic neuronal activation, we found that exercise activates leptin receptor-positive neurons in the ventromedial hypothalamic nucleus, involved in homeostatic control of energy balance. FosB immunoreactivity in the ventromedial hypothalamic nucleus is decreased in sedentary mice exposed to HFD but is increased in exercised mice independent of adiposity. To determine whether the antiobesity effects of voluntary exercise improve central nervous system (CNS) leptin action, we measured the anorectic and weight reducing effects of intracerebroventricular (ICV) leptin in sedentary and exercised mice exposed to HFD (EH), as well as in sedentary mice that have been calorie restricted (SR) to match the fat mass of EH mice. ICV leptin was ineffective in lowering food intake and body weight (BW) in sedentary mice exposed to HFD mice. The anorectic potency of leptin was partially restored in EH and SR groups. However, ICV leptin significantly lowered BW in EH but not SR mice. Thus, exercise leads to the maintenance of a lower BW and leaner composition, as well as to improved CNS leptin action, independent of fat mass. These results support the notion that physical exercise directly influences the responsiveness of the CNS circuits involved in energy homeostasis by allowing the defense of a lowered BW.

  13. Study of Blood Leptin Levels before and After Treatment with Metformin in Diabetes Type Ii Patients

    Directory of Open Access Journals (Sweden)

    R Didehdar

    2005-04-01

    Full Text Available Introduction: Leptin is a fat tissue hormone that has 176 amino acids with a molecular weight of 16 KD . Leptin has effects on the hypothalamus and peripheral tissues resulting in decreased food absorption and increased energy consumption that finally reduces the body weight and BMI. The aim of this research was to investigate the blood levels of leptin before and after treatment with Metformin in type II diabetic patients. Methods: 25 type II diabetic patients without any previous drug treatment history were investigated. This study was a clinical trail before and after treatment with Metformin. Results: There was no particular difference in BMI, average body weight, fat mass and free fat mass before and after treatment. Similarly, the difference in concentration levels of blood glucose, cholesterol, tri-glycerides and LDL-cholesterol before and after treatment was not statistically significant. Also, there was no difference in the average concentration of leptin and insulin before and after treatment Conclusion: This result showed that although metformin decreased glucose and lipid levels during the treatment period, (1 month it did not have an effect on leptin, Insulin and other related factors during treatment.;

  14. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  15. How about food irradiation? Its history and usefulness. (3) Irradiation effects on food and decrease in fungi

    International Nuclear Information System (INIS)

    Ito, Hitoshi

    2006-01-01

    Inhibiting germination of vegetables and grade control of maturity of fruits, destroy of insect pest and parasite, disinfection of meats and fishes, bactericidal action of dry foods such as spices, and taste and color change of irradiated foods and perfect bactericidal action are stated. Application of food irradiation contains inhibiting germination, insecticidal action, sterilization of insect pest, grade control of maturity, inhibition of food poisoning, decrease in fungi, improvement of properties, and perfect bactericidal action. Each treatment of foods is described by the effects of three exposure doses such as the low exposure dose until 1 kGy, middle exposure dose from 1 to 10 kGy and high from 10 to 75 kGy. (S.Y.)

  16. Nudge to nobesity I: Minor changes in accessibility decrease food intake

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2011-06-01

    Full Text Available Very small but cumulated decreases in food intake may be sufficient to erase obesity over a period of years. We examine the effect of slight changes in the accessibility of different foods in a pay-by-weight-of-food salad bar in a cafeteria serving adults for the lunch period. Making a food slightly more difficult to reach (by varying its proximity by about 10 inches or changing the serving utensil (spoon or tongs modestly but reliably reduces intake, in the range of 8-16%. Given this effect, it is possible that making calorie-dense foods less accessible and low-calorie foods more accessible over an extended period of time would result in significant weight loss.

  17. Water incorporated into a food but not served with a food decreases energy intake in lean women.

    Science.gov (United States)

    Rolls, B J; Bell, E A; Thorwart, M L

    1999-10-01

    Previous research showed that decreasing the energy density (kJ/g) of foods by adding water to them can lead to reductions in energy intake. Few studies have examined how water consumed as a beverage affects food intake. This study examined the effects of water, both served with a food and incorporated into a food, on satiety. In a within-subjects design, 24 lean women consumed breakfast, lunch, and dinner in our laboratory 1 d/wk for 4 wk. Subjects received 1 of 3 isoenergetic (1128 kJ) preloads 17 min before lunch on 3 d and no preload on 1 d. The preloads consisted of 1) chicken rice casserole, 2) chicken rice casserole served with a glass of water (356 g), and 3) chicken rice soup. The soup contained the same ingredients (type and amount) as the casserole that was served with water. Decreasing the energy density of and increasing the volume of the preload by adding water to it significantly increased fullness and reduced hunger and subsequent energy intake at lunch. The equivalent amount of water served as a beverage with a food did not affect satiety. Energy intake at lunch was 1209 +/- 125 kJ after the soup compared with 1657 +/- 148 and 1639 +/- 148 kJ after the casserole with and without water, respectively. Subjects did not compensate at dinner for this reduction in lunch intake. Consuming foods with a high water content more effectively reduced subsequent energy intake than did drinking water with food.

  18. [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.

  19. Leptin in humans: lessons from translational research1234

    OpenAIRE

    Blüher, Susann; Mantzoros, Christos S

    2009-01-01

    Leptin has emerged over the past decade as a key hormone in not only the regulation of food intake and energy expenditure but also in the regulation of neuroendocrine and immune function as well as the modulation of glucose and fat metabolism as shown by numerous observational and interventional studies in humans with (complete) congenital or relative leptin deficiency. These results have led to proof-of-concept studies that have investigated the effect of leptin administration in subjects wi...

  20. Differential Effects of Leptin on the Invasive Potential of Androgen-Dependent and -Independent Prostate Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Dayanand D. Deo

    2008-01-01

    Full Text Available Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP cells as well as androgen-insensitive (PC-3 and DU-145 cells. At a concentration of 200_nm, LNCaP cells showed a significant increase (20% above control; P<.0001 in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P<.01 to P<.0001 dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.

  1. Studies on leptin and its feedback system for weight regulation

    International Nuclear Information System (INIS)

    Lei Chengzhi

    2002-01-01

    Recently the hormone leptin has been regarded as hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The role of leptin and its feedback system in man is partly revealed. Hypothalamic centers appear to control appetite, metabolic rate and activity level in a co-ordinate manner. Within the hypothalamus, known weight regulatory molecules include leptin, neuropeptide Y and POMC. The authors integrated new information into a revised model for understanding this important regulatory process. The model of energy homeostasis propose that the interaction of leptin with various neuroendocrine pathway in the brain and in the periphery to affect food-take

  2. Leptin's effect on taste bud calcium responses and transmitter secretion.

    Science.gov (United States)

    Meredith, Tricia L; Corcoran, Alan; Roper, Stephen D

    2015-05-01

    Leptin, a peptide hormone released by adipose tissue, acts on the hypothalamus to control cravings and appetite. Leptin also acts to decrease taste responses to sweet substances, though there is little detailed information regarding where leptin acts in the taste transduction cascade. The present study examined the effects of leptin on sweet-evoked responses and neuro transmitter release from isolated taste buds. Our results indicate that leptin moderately decreased sweet-evoked calcium mobilization in isolated mouse taste buds. We also employed Chinese hamster ovary biosensor cells to examine taste transmitter release from isolated taste buds. Leptin reduced ATP and increased serotonin release in response to sweet stimulation. However, leptin has no effect on bitter-evoked transmitter release, further showing that the action of leptin is sweet specific. Our results support those of previous studies, which state that leptin acts on taste tissue via the leptin receptor, most likely on Type II (Receptor) cells, but also possibly on Type III (Presynaptic) cells. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Adiponectin, Leptin, and Leptin Receptor in Obese Patients with Type 2 Diabetes Treated with Insulin Detemir

    Directory of Open Access Journals (Sweden)

    Paweł Olczyk

    2017-07-01

    Full Text Available The aim of the present study is to quantitatively assess the expression of selected regulatory molecules, such as leptin, leptin receptor, and adiponectin in the blood of obese patients with type 2 diabetes both before treatment and after six months of pharmacological therapy with the long-lasting insulin analogue, insulin detemir. A significant decrease in the analysed regulatory molecules, i.e., leptin receptor and adiponectin, was found in blood plasma of the patients with untreated type 2 diabetes. These changes were accompanied by an increase in plasma leptin concentrations. Insulin treatment resulted in the normalization of plasma leptin receptor and adiponectin concentrations. The circulating leptin level did not change following anti-diabetic therapy with insulin detemir. Gender was a significant factor modifying the circulating level of all the analysed regulatory active compounds. Bioinformatic analysis was performed using Matlab with the Signal Processing Toolbox. The conducted discriminant analysis revealed that the leptin receptor, Δw(19, and adiponectin, Δw(21, were the parameters undergoing the most significant quantitative changes during the six-month therapy with insulin detemir. The conducted examinations indicated the contribution of adipocytokines—the biologically-active mediators of systemic metabolism, such as leptin and adiponectin in the pathomechanism of disorders being the basis for obesity which leads to development of insulin resistance, which, in turn, results in the occurrence of type 2 diabetes.

  4. The neuroanatomical function of leptin in the hypothalamus.

    Science.gov (United States)

    van Swieten, M M H; Pandit, R; Adan, R A H; van der Plasse, G

    2014-11-01

    The anorexigenic hormone leptin plays an important role in the control of food intake and feeding-related behavior, for an important part through its action in the hypothalamus. The adipose-derived hormone modulates a complex network of several intercommunicating orexigenic and anorexigenic neuropeptides in the hypothalamus to reduce food intake and increase energy expenditure. In this review we present an updated overview of the functional role of leptin in respect to feeding and feeding-related behavior per distinct hypothalamic nuclei. In addition to the arcuate nucleus, which is a major leptin sensitive hub, leptin-responsive neurons in other hypothalamic nuclei, including the, dorsomedial-, ventromedial- and paraventricular nucleus and the lateral hypothalamic area, are direct targets of leptin. However, leptin also modulates hypothalamic neurons in an indirect manner, such as via the melanocortin system. The dissection of the complexity of leptin's action on the networks involved in energy balance is subject of recent and future studies. A full understanding of the role of hypothalamic leptin in the regulation of energy balance requires cell-specific manipulation using of conditional deletion and expression of leptin receptors. In addition, optogenetic and pharmacogenetic tools in combination with other pharmacological (such as the recent discovery of a leptin receptor antagonist) and neuronal tracing techniques to map the circuit, will be helpful to understand the role of leptin receptor expressing neurons. Better understanding of these circuits and the involvement of leptin could provide potential sites for therapeutic interventions in obesity and metabolic diseases characterized by dysregulation of energy balance. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Leptin and Reproduction: Past Milestones, Present Undertakings and Future Endeavors

    Science.gov (United States)

    Chehab, Farid F.

    2014-01-01

    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 that 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 AgRP/NPY neurons project onto GnRH and kisspeptin neurons, allowing a crosstalk between food intake and reproduction. Finally, whereas 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. 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 next decade to shed new light on these complex and essential pathways. PMID:25118207

  6. Leptin and cancer: Pathogenesis and modulation

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults

    DEFF Research Database (Denmark)

    Andriessen, Charlotte; Christensen, Pia; Nielsen, Lone Vestergaard

    2018-01-01

    consumption (p meal. An interaction effect (visit x time) was found for hunger ratings (p ... preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p ....9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p meal and by 17.4% and 22.7% after the meal (p 

  9. Increased tissue leptin hormone level and mast cell count in skin tags: A possible role of adipoimmune in the growth of benign skin growths

    Directory of Open Access Journals (Sweden)

    El Safoury Omar

    2010-01-01

    Full Text Available Background: Skin tags (ST are common tumors. They mainly consist of loose fibrous tissue and occur on the neck and major flexures as small, soft, pedunculated protrusions. Decrease in endocrine, hormone level and other factors are thought to play a role in the evolution of ST. Leptin is an adipocyte-derived hormone that acts as a major regulatory hormone for food intake and energy homeostasis. Leptin deficiency or resistance can result in profound obesity and diabetes in humans. A role of mast cell in the pathogenesis of ST is well recognized. Aims: To investigate the role of leptin in the pathogenesis of ST and to clarify whether there is a correlation between mast cell count and leptin level in ST. Methods: Forty-five skin biopsies were taken from 15 patients with ST. From each patient, a biopsy of a large ST (length >4 mm, a small ST (length <2 mm and a normal skin biopsy (as a control were taken. The samples were processed for leptin level. Skin biopsies were stained with hematoxylin and eosin and toluidine blue-uranyl nitrate metachromatic method for mast cell count was used. Results: There was a significant increased level of leptin in the ST compared to the normal skin. It was highly significant in small ST than in big ST (P = 0.0001 and it was highly significant in small and big ST compared to controls, P = 0.0001 and P = 0.001, respectively. There was a significant increase in mast cell count in the ST, which did not correlate with the increased levels of leptin. Conclusion: This is the first report to demonstrate that tissue leptin may play a role in the pathogenesis of ST. The significant increase in the levels of leptin and mast cell count in ST may indicate a possible role of adipoimmune in the benign skin growths.

  10. Leptin and adiponectin in the female life course

    Directory of Open Access Journals (Sweden)

    S.B. Lecke

    2011-05-01

    Full Text Available Adipose tissue secretes a variety of adipokines, including leptin and adiponectin, which are involved in endocrine processes regulating glucose and fatty metabolism, energy expenditure, inflammatory response, immunity, cardiovascular function, and reproduction. The present article describes the fluctuations in circulating leptin and adiponectin as well as their patterns of secretion in women from birth to menopause. During pregnancy, leptin and adiponectin seem to act in an autocrine/paracrine fashion in the placenta and adipose tissue, playing a role in the maternal-fetal interface and contributing to glucose metabolism and fetal development. In newborns, adiponectin levels are two to three times higher than in adults. Full-term newborns have significantly higher leptin and adiponectin levels than preterms, whereas small-for-gestational-age infants have lower levels of these adipokines than adequate-for-gestational-age newborns. However, with weight gain, leptin concentrations increase significantly. Children between 5 and 8 years of age experience an increase in leptin and a decrease in adiponectin regardless of body mass index, with a reversal of the newborn pattern for adiponectin: plasma adiponectin levels at age five are inversely correlated with percentage of body fat. In puberty, leptin plays a role in the regulation of menstrual cycles. In adults, it has been suggested that obese individuals exhibit both leptin resistance and decreased serum adiponectin levels. In conclusion, a progressive increase in adiposity throughout life seems to influence the relationship between leptin and adiponectin in women.

  11. 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.

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-meng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Han-wen [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Kou, Hao [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wen, Yin-xian [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Shen, Lang; Pei, Ling-guo; Zhou, Jin [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Zhang, Yuan-zhen [Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-11-15

    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.

  14. Leptin (Obesity Protein) and Breast Cancer Metastasis

    National Research Council Canada - National Science Library

    Surmacz, Eva

    2002-01-01

    ...). Leptin, a 16 kDa protein product of the OB (obesity) gene is a cytokine reported to be secreted mainly from adipocytes and has been shown to control body fat mass and food intake by providing information to the central nervous system (2...

  15. Improved meal presentation increases food intake and decreases readmission rate in hospitalized patients.

    Science.gov (United States)

    Navarro, Daniela Abigail; Boaz, Mona; Krause, Ilan; Elis, Avishay; Chernov, Karina; Giabra, Mursi; Levy, Miriam; Giboreau, Agnes; Kosak, Sigrid; Mouhieddine, Mohamed; Singer, Pierre

    2016-10-01

    Reduced food intake is a frequent problem at a hospital setting, being a cause and/or consequence of malnutrition. Food presentation can affect food intake and induce nutritional benefit. To investigate the effect of improved meal presentation supported by gastronomy expertise on the food intake in adults hospitalized in internal medicine departments. Controlled before and after study. Two hundred and six newly hospitalized patients in internal medicine departments were included and divided in two groups, a) control: receiving the standard lunch from the hospital and b) experimental: receiving a lunch improved in terms of presentation by the advices received by the Institut Paul Bocuse, Ecully, Lyon, France together with the hospital kitchen of the Beilinson Hospital, without change in the composition of the meal. The amount of food left at the participants' plates was estimated using the Digital Imaging Method, which consisted in photographing the plates immediately to previous tray collection by the researcher. In addition, the nutritionDay questionnaire was used to measure other variables concerned to their food intake during hospitalization. Charlson Comorbidity Index was calculated. There was no significant difference between the groups regarding demography or Charlson Comorbidity Index. Patients who received the meal with the improved presentation showed significantly higher food intake than those who received the standard meal, despite reported loss in appetite. Participants from the experimental group left on their plate less starch (0.19 ± 0.30 vs. 0.52 + 0.41) (p  0.05). Both of the groups were asked how hungry they were before the meal and no significance was shown. More participants from the experimental group reported their meal to be tasty in comparison to those in the control group (49.5% vs. 33.7% p < 0.005). Length of stay was not different but readmission rate decreased significantly in the study group (p < 0.02) from 31.2% to 13

  16. 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

  17. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    International Nuclear Information System (INIS)

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-01-01

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  18. Effects of n-3 Polyunsaturated Fatty Acid Supplementation on Serum Leptin Levels, Appetite Sensations, and Intake of Energy and Macronutrients in Obese People: A Randomized Clinical Trial.

    Science.gov (United States)

    Payahoo, L; Ostadrahimi, A; Farrin, N; Khaje-Bishak, Y

    2017-10-05

    Obesity is a common health problem. Appetite is one of the main obesity-controlling factors that can be influenced by leptin. Leptin reduces food intake and accelerates energy expenditure. Leptin levels can be affected by dietary factors such as fats, special amino acids, and fructose. This study aimed to determine the effects of polyunsaturated fatty acid n-3 (PUFA n-3) supplementation on serum leptin levels, appetite sensations, and dietary intakes in obese people. This study was performed on 60 obese individuals with body mass index (BMI) 30 (kg/m 2 ) and above in 2012 in Tabriz, Iran. The participants were randomly allocated to the intervention (consumed two capsules containing 1 g/day n-3 fatty acids [180 mg EPA, 120 mg DHA] for 4 weeks) and control groups. Serum leptin levels were assessed by ELISA method, and visual analogue scale (VAS) questionnaire was completed for evaluating appetite sensations. The mean caloric [before = 1,575.39 (600), after = 1,236.14 (448.40)] and macronutrient intakes were decreased significantly in the intervention group (p macronutrient intakes, probably through the modulating of satiety. The short period of study caused the nonsignificant changes in BMI and circulatory leptin. Further studies are needed to confirm these results.

  19. Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

    Science.gov (United States)

    Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

    2018-05-25

    Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

  20. Warm ambient temperature decreases food intake in a simulated office setting: A pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Molly eBernhard

    2015-08-01

    Full Text Available Background: We hypothesized that exposure to temperatures above the thermoneutral zone would decrease food intake in young adults in a sedentary office environment over a 2-hour period. Methods: Participants wearing standardized clothing were randomized to perform routine office work in either within the thermoneutral zone, considered control (19-20°C, or above the thermoneutral zone considered warmer (26-27°C treatment in parallel-group design (n=11 and 9, respectively. Thermal images of the inner canthus of their eye and middle finger nail bed, representing proxies of core and peripheral temperatures, respectively, were taken at baseline, 1st, and 2nd hour during this lunchtime study. Relative heat dissipation was estimated as peripheral temperature. General linear models were conducted to examine the effects of thermal treatment the calories intake and potential mediation. Researchers conducted the trial registered as NCT02386891 at Clinicaltrials.gov during April- May 2014. Results: During the 2 hours stay in different ambient temperatures, the participants in the control conditions ate 99.5 kcal more than those in the warmer conditions; however, the difference was not statistically significant. Female participants ate about 350 kcal less than the male participants (P=0.024 in both groups and there was no significant association between calories intake and participant’s BMI. After controlling for thermal treatment, gender and BMI, the participant’s peripheral temperature was significantly associated with calories intake (p=0.002, suggesting a mediating effect. Specifically, for every 1°C increase in peripheral temperature indicating reduced heat dissipation, participants ate 85.9 kcal less food. Conclusions: This pilot study provided preliminary evidence of effects of thermal environment on food intake and the decreased food intake in the experimental (warmer environment is potentially mediated through thermoregulatory mechanisms.

  1. Warm Ambient Temperature Decreases Food Intake in a Simulated Office Setting: A Pilot Randomized Controlled Trial.

    Science.gov (United States)

    Bernhard, Molly C; Li, Peng; Allison, David B; Gohlke, Julia M

    2015-01-01

    We hypothesized that exposure to temperatures above the thermoneutral zone (TNZ) would decrease food intake in young adults in a sedentary office environment over a 2-h period. Participants wearing standardized clothing were randomized to perform routine office work in the TNZ, considered control (19-20°C), or above the TNZ considered warmer (26-27°C) using a parallel-group design (n = 11 and 9, respectively). Thermal images of the inner canthus of their eye and middle finger nail bed, representing proxies of core and peripheral temperatures, respectively, were taken at baseline, first, and second hour during this lunchtime study. Heat dissipation was estimated using peripheral temperature. General linear models were built to examine the effects of thermal treatment on caloric intake and potential mediation by heat dissipation. Researchers conducted the trial registered as NCT02386891 at Clinicaltrials.gov during April to May 2014. During the 2-h stay in different ambient temperatures, the participants in the control conditions ate 99.5 kcal more than those in the warmer conditions; however, the difference was not statistically significant. Female participants ate about 350 kcal less than the male participants (p = 0.024) in both groups and there was no significant association between caloric intake and participant's body mass index (BMI). After controlling for thermal treatment, gender and BMI, the participant's peripheral temperature was significantly associated with caloric intake (p = 0.002), suggesting a mediating effect. Specifically, for every 1°C increase in peripheral temperature suggesting increased heat dissipation, participants ate 85.9 kcal less food. This pilot study provided preliminary evidence of effects of thermal environment on food intake. It suggests that decreased food intake in the experimental (warmer) environment is potentially mediated through thermoregulatory mechanisms.

  2. 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

  3. Changes in circulating leptin levels during the initial stage of cessation are associated with smoking relapse.

    Science.gov (United States)

    Lemieux, Andrine; Nakajima, Motohiro; Hatsukami, Dorothy K; Allen, Sharon; al'Absi, Mustafa

    2015-09-01

    Leptin has been linked to tobacco craving and withdrawal-related symptoms. Very few studies have examined leptin prospectively in both male and female nonsmokers and smokers. We examine leptin concentrations prospectively in both male and female nonsmokers and smokers to assess the associations of leptin with psychological symptoms and smoking relapse during ad libitum smoking, the first 48 h post quit, and 4 weeks post-cessation. Self-report psychological, anthropomorphic, and biological measures (cotinine, carbon monoxide, and plasma leptin) were collected before and after 48 h of smoking abstinence. Smokers were stratified at 28 days post quit as abstinent or relapsed if they had smoked daily for seven consecutive days at any point in the 28 days. Leptin concentration (square root transformed ng/ml) increased over the 48-h abstinence, but only in female abstainers. In contrast, leptin was very stable across time for nonsmokers, relapsers, and males. Cox regression supported that increased leptin was associated with decreased risk of relapse. Leptin was correlated negatively with withdrawal symptoms for abstainers only. Females produce more leptin than males and this level increases from ad libitum smoking to 48-h post quit. The current analysis indicates that a leptin increase early in cessation predicts abstinence. The increase in women, but not men, in response to abstinence provides further evidence of important gender differences. The negative correlation between leptin and withdrawal symptoms indicates a possible protective effect of leptin. Further research is ongoing to elucidate the psychological and biological determinants of this effect.

  4. Shp2 signaling in POMC neurons is important for leptin's actions on blood pressure, energy balance, and glucose regulation.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Ebaady, Sabira E; Sessums, Price O; Abraham, Ralph S; Elmquist, Joel K; Lowell, Bradford B; Hall, John E

    2014-12-15

    Previous studies showed that Src homology-2 tyrosine phosphatase (Shp2) is an important regulator of body weight. In this study, we examined the impact of Shp2 deficiency specifically in proopiomelanocortin (POMC) neurons on metabolic and cardiovascular function and on chronic blood pressure (BP) and metabolic responses to leptin. Mice with Shp2 deleted in POMC neurons (Shp2/Pomc-cre) and control mice (Shp2(flox/flox)) were implanted with telemetry probes and venous catheters for measurement of mean arterial pressure (MAP) and leptin infusion. After at least 5 days of stable control measurements, mice received leptin infusion (2 μg·kg(-1)·day(-1) iv) for 7 days. Compared with Shp2(flox/flox) controls, Shp2/Pomc-cre mice at 22 wk of age were slightly heavier (34 ± 1 vs. 31 ± 1 g) but consumed a similar amount of food (3.9 ± 0.3 vs. 3.8 ± 0.2 g/day). Leptin infusion reduced food intake in Shp2(flox/flox) mice (2.6 ± 0.5 g) and Shp2/Pomc-cre mice (3.2 ± 0.3 g). Despite decreasing food intake, leptin infusion increased MAP in control mice, whereas no significant change in MAP was observed in Shp2/Pomc-cre mice. Leptin infusion also decreased plasma glucose and insulin levels in controls (12 ± 1 to 6 ± 1 μU/ml and 142 ± 12 to 81 ± 8 mg/100 ml) but not in Shp2/Pomc-cre mice. Leptin increased V̇o2 by 16 ± 2% in controls and 7 ± 1% in Shp2/Pomc-cre mice. These results indicate that Shp2 signaling in POMC neurons contributes to the long-term BP and antidiabetic actions of leptin and may play a modest role in normal regulation of body weight. Copyright © 2014 the American Physiological Society.

  5. Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

    Science.gov (United States)

    Moerke, Megan J; Banks, Matthew L; Cheng, Kejun; Rice, Kenner C; Negus, S Stevens

    2017-12-01

    Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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.

  7. Measurement of Radiocesium Decreasing Ratios in Some Crops after Food Processing

    Energy Technology Data Exchange (ETDEWEB)

    Uchida, Shigeo; Tagami, Keiko [National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263-7444 (Japan)

    2014-07-01

    Radiocesium concentrations in foods are of great concern after the Fukushima Daiichi nuclear power plant (FDNPP) accident to avoid receiving additional dose. Food monitoring has been carried out and, if there is any food exceeding the standard limit of 100 Bq/kg of radiocesium ({sup 134}Cs+{sup 137}Cs), the food name together with the producing district has been reported immediately by the Ministry of Health, Labor and Welfare. Every month, about 20,000 samples have been measured their radioactivities, and the most recent data of August 2013 showed that only foods from wild sometimes exceeds the standard limits. However, public people worry about the radiocesium concentrations in foods, although the value were lower than 100 Bq/kg; and thus, one of their concerns is still how to remove radiocesium from foods. Unfortunately, however, there were not so many data for crops common in Japan before the FDNPP accident. To provide more data, we've been collecting data. Samples were obtained from wild, that is, mugwort, giant butter-bur, young bamboo shoot and chestnut, collected in Chiba or Fukushima Prefectures in Japan in 2013. Mugwort and giant butter-bur samples were separated into three portions to make raw, washed and boiled (2.5 min) samples. Young bamboo shoot and chestnut samples were separated into two portions to make raw and boiled sub-samples. All samples were oven-dried at 80 deg. C and each sample was pulverized and mixed well. After transfer the sample to a plastic container, the radioactivity concentration was measured by a Ge detecting system. The results showed that radiocesium concentrations after boiling decreased by 50-60% for mugwort (n=3), 15-40% for petioles of giant butter-bur (n=3), 20-35% for young bamboo shoot (n=7), and 0-20% for chestnut (n=3). These data were compared with recently reported values collected in Japan complied by Radioactive Waste management Funding and Research Center (2013), and our data were within the range of

  8. TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

    Directory of Open Access Journals (Sweden)

    Yong Gao

    2017-01-01

    Full Text Available The molecular mechanisms underlying acute leptin and serotonin 2C receptor-induced hypophagia remain unclear. Here, we show that neuronal and pro-opiomelanocortin (Pomc-specific loss of transient receptor potential cation 5 (TrpC5 subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons is also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr agonists. The loss of acute anorexigenic effects of these receptors is concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance are blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity, as well as energy balance, feeding behavior, and glucose metabolism.

  9. Role of GABA Release From Leptin Receptor-Expressing Neurons in Body Weight Regulation

    Science.gov (United States)

    Xu, Yuanzhong; O'Brien, William G.; Lee, Cheng-Chi; Myers, Martin G.

    2012-01-01

    It is well established that leptin regulates energy balance largely through isoform B leptin receptor-expressing neurons (LepR neurons) in the brain and that leptin activates one subset of LepR neurons (leptin-excited neurons) while inhibiting the other (leptin-inhibited neurons). However, the neurotransmitters released from LepR neurons that mediate leptin action in the brain are not well understood. Previous results demonstrate that leptin mainly acts on γ-aminobutyric acid (GABA)ergic neurons to reduce body weight, and that leptin activates proopiomelanocortin neuron activity by reducing GABA release onto these neurons, suggesting a body weight-promoting role for GABA released from leptin-inhibited neurons. To directly examine the role of GABA release from LepR neurons in body weight regulation, mice with disruption of GABA release specifically from LepR neurons were generated by deletion of vesicular GABA transporter in LepR neurons. Interestingly, these mice developed mild obesity on chow diet and were sensitive to diet-induced obesity, which were associated with higher food intake and lower energy expenditure. Moreover, these mice showed blunted responses in both food intake and body weight to acute leptin administration. These results demonstrate that GABA plays an important role in mediating leptin action. In combination with the previous studies that leptin reduces GABA release onto proopiomelanocortin neurons through leptin-inhibited neurons and that disruption of GABA release from agouti gene-related protein neurons, one subset of LepR-inhibited neurons, leads to a lean phenotype, our results suggest that, under our experimental conditions, GABA release from leptin-excited neuron dominates over leptin-inhibited ones. PMID:22334723

  10. Influence of Antioxidants on Leptin Metabolism and its Role in the Pathogenesis of Obesity.

    Science.gov (United States)

    Mangge, Harald; Ciardi, Christian; Becker, Kathrin; Strasser, Barbara; Fuchs, Dietmar; Gostner, Johanna M

    2017-01-01

    Obesity is associated with low-grade inflammation. Leptin, a hormone made by fat cells regulates appetite and hunger and thus food intake behavior. Interestingly, , food preservatives like sodium sulfite and sodium benzoate and also natural colorant and spice compounds such as curcumin were found to decrease the release of leptin in murine 3T3-L1 adipocytes, after co-incubation with LPS, which was added to mimic the pro-inflammatory status in obesity. Several of these compounds are well known food antioxidants.Whilst reducing oxidation events is beneficial in states of elevated oxidative stress, overexposure to food antioxidant can lead to adverse effects. There are hints from in vivo data, that antioxidant stress in younger age plays a role in the development of adiposity in later life. The insufficient exposure to oxidizing compounds like reactive oxygen species (ROS) cannot only cause an insufficient burning of calories but there is also a link to the regulation of food intake behavior. If the in vitro findings can be extrapolated to the in vivo situation, consumption of antioxidant supplemented food could lead to decreased leptin release and contribute to an obesogenic environment. This aspect sheds some new critical light on the potential role of an antioxidant-enriched nutrition in the obesity epidemic during the past few centuries. Doing sports could represent not only a proper strategy to initiate physiological ROS production and burning of calories, but also may shift the hormone milieu towards a reduction of hunger feelings and thus reduce appetite and food intake.

  11. High altitude induced anorexia: effect of changes in leptin and oxidative stress levels.

    Science.gov (United States)

    Vats, Praveen; Singh, Vijay Kumar; Singh, Som Nath; Singh, Shashi Bala

    2007-01-01

    High altitude (HA) exposure usually leads to a significant weight loss in non-acclimatized humans. Anorexia is believed to be the main cause of this body weight loss. Appetite regulatory peptides, i.e. leptin and neuropeptide Y play a key role in food intake and energy homeostasis. Recent studies suggests increased oxidative stress during HA exposure. In present study effect of HA exposure on levels of leptin and NPY was evaluated along with N-acetyl cysteine (NAC) and vitamin E supplementation in relation to food intake and body weight changes. The study was conducted on 30 healthy male volunteers (age 19-29 years). Subjects were divided randomly into three groups of 10 each. Group 1 (placebo) supplemented with 400 mg of calcium gluconate, group 2 and 3 were supplemented with 400 mg of NAC and 400 mg vitamin E, respectively per day. The study was conducted at low altitude (320 m, Phase I), at HA 3600 m (Phase II) and at an altitude of 4580 m (Phase III). On HA exposure significant reduction in plasma leptin levels was observed in all the groups on day 2 (Phase II) along with decrease in food intake and reduction in body weight. Statistically significant increase in blood malondialdehyde (MDA) levels was seen in all the groups on HA exposure (Phase II, Day 2), but the maximum increase was in case of placebo group (65.1%) on day 2 (Phase II) in comparison to low altitude values. The decrease in energy intake was almost same in all the groups indicating that antioxidant supplementation did not provide any protection against HA anorexia. From the study, it may be concluded that leptin and oxidative stress possibly are not the key players for HA anorexia.

  12. Modulation of the mesolimbic dopamine system by leptin.

    Science.gov (United States)

    Opland, Darren M; Leinninger, Gina M; Myers, Martin G

    2010-09-02

    Nutritional status modulates many forms of reward-seeking behavior, with caloric restriction increasing the drive for drugs of abuse as well as for food. Understanding the interactions between the mesolimbic dopamine (DA) system (which mediates the incentive salience of natural and artificial rewards) and the neural and hormonal systems that sense and regulate energy balance is thus of significant importance. Leptin, which is produced by adipocytes in proportion to fat content as a hormonal signal of long-term energy stores, acts via its receptor (LepRb) on multiple populations of central nervous system neurons to modulate neural circuits in response to body energy stores. Leptin suppresses feeding and plays a central role in the control of energy balance. In addition to demonstrating that leptin modulates hypothalamic and brainstem circuits to promote satiety, recent work has begun to explore the mechanisms by which leptin influences the mesolimbic DA system and related behaviors. Indeed, leptin diminishes several measures of drug and food reward, and promotes a complex set of changes in the mesolimbic DA system. While many of the details remain to be worked out, several lines of evidence suggest that leptin regulates the mesolimbic DA system via multiple neural pathways and processes, and that distinct sets of LepRb neurons each modulate unique aspects of the mesolimbic DA system and behavior in response to leptin. 2010 Elsevier B.V. All rights reserved.

  13. The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

    Science.gov (United States)

    Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

    2014-10-01

    Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

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

    Directory of Open Access Journals (Sweden)

    El-Shazly AN

    2015-12-01

    Full Text Available Ahmed Nabih El-Shazly,1 Soha Abd El-Hady Ibrahim,1 Ghada Mohamed El-Mashad,2 Jehan H Sabry,3 Nashwa Said Sherbini11Department of Pediatrics, Faculty of Medicine, Benha University, Banha, 2Department of Pediatrics, Faculty of Medicine, Menoufia University, Shibin Al Kawm, 3Department of Clinical and Chemical Pathology, Faculty of Medicine, Benha University, Banha, Egypt Introduction: Zinc is an essential trace element for human nutrition, and its deficiency is associated with anorexia, poor food efficiency, growth retardation, and impaired neurological and immune systems. The zinc-deficiency rate is particularly high in many disease states, such as with end-stage renal disease patients undertaking hemodialysis. The aim of this study was to determine the effect of zinc supplementation on body mass index (BMI and serum levels of zinc and leptin in pediatric hemodialysis patients. Patients and methods: This was a prospective clinical trial study in which 60 hemodialysis patients were randomly divided into two groups: group I received 50–100 mg zinc sulfate (equivalent to 11–22 mg elemental zinc according to age, sex, and nutritional status of the child; and group II received placebo (cornstarch twice daily for 90 days. Anthropometric measurements were taken, and serum zinc and leptin levels were determined by colorimetric test with 5-Br-3'-phosphoadenosine-5'-phosphosulfate and enzyme-linked immunosorbent assay, respectively, at days 0 and 90 of the study. Results: Zinc supplementation resulted in a significant increase in mean serum zinc level and BMI. Serum leptin decreased significantly after supplementation in children under hemodialysis. A significant negative correlation was observed between serum zinc and leptin levels as a result of zinc supplementation. Conclusion: There was an increase in serum zinc level and BMI and decreased serum leptin after zinc supplementation in children under hemodialysis. Keywords: serum zinc, serum leptin

  15. 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.

  16. 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

  17. Leptin production during early starvation in lean and obese women.

    Science.gov (United States)

    Klein, S; Horowitz, J F; Landt, M; Goodrick, S J; Mohamed-Ali, V; Coppack, S W

    2000-02-01

    We evaluated abdominal adipose tissue leptin production during short-term fasting in nine lean [body mass index (BMI) 21 +/- 1 kg/m(2)] and nine upper body obese (BMI 36 +/- 1 kg/m(2)) women. Leptin kinetics were determined by arteriovenous balance across abdominal subcutaneous adipose tissue at 14 and 22 h of fasting. At 14 h of fasting, net leptin release from abdominal adipose tissue in obese subjects (10.9 +/- 1.9 ng x 100 g tissue x (-1) x min(-1)) was not significantly greater than the values observed in the lean group (7.6 +/- 2.1 ng x 100 g(-1) x min(-1)). Estimated whole body leptin production was approximately fivefold greater in obese (6.97 +/- 1.18 microg/min) than lean subjects (1.25 +/- 0.28 microg/min) (P production rates decreased in both lean and obese groups (to 3.10 +/- 1.31 and 10.5 +/- 2.3 ng x 100 g adipose tissue(-1) x min(-1), respectively). However, the relative declines in both arterial leptin concentration and local leptin production in obese women (arterial concentration 13.8 +/- 4.4%, local production 10.0 +/- 12.3%) were less (P lean women (arterial concentration 39.0 +/- 5.5%, local production 56.9 +/- 13.0%). This study demonstrates that decreased leptin production accounts for the decline in plasma leptin concentration observed after fasting. However, compared with lean women, the fasting-induced decline in leptin production is blunted in women with upper body obesity. Differences in leptin production during fasting may be responsible for differences in the neuroendocrine response to fasting previously observed in lean and obese women.

  18. 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.

  19. The leptin system and its expression at different nutritional and pregnant stages in lined seahorse (Hippocampus erectus).

    Science.gov (United States)

    Zhang, Huixian; Qin, Geng; Zhang, Yanhong; Li, Shuisheng; Lin, Qiang

    2016-10-15

    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. © 2016. Published by The Company of Biologists Ltd.

  20. Visual food cues decrease postprandial glucose concentrations in lean and obese men without affecting food intake and related endocrine parameters.

    Science.gov (United States)

    Brede, Swantje; Sputh, Annika; Hartmann, Ann-Christin; Hallschmid, Manfred; Lehnert, Hendrik; Klement, Johanna

    2017-10-01

    The abundance of highly palatable food items in our environment represents a possible cause of overconsumption. Neuroimaging studies in humans have demonstrated that watching pictures of food increases activation in brain areas involved in homeostatic and hedonic food cue processing. Nevertheless, the impact of food cues on actual food intake and metabolic parameters has not been systematically investigated. We tested the hypothesis that watching high-calorie food cues increases food intake and modifies anticipatory blood parameters in lean and especially in obese men. In 20 normal-weight and 20 obese healthy fasted men, we assessed the effects of watching pictures of high-calorie food items versus neutral contents on food intake measured during a standardized test buffet and subsequent snacking as well as on glucose homeostasis and endocrine parameters. Compared to neutral pictures, viewing food pictures reduced postprandial blood glucose concentrations in lean (p = 0.016) and obese (p = 0.044) subjects, without any differences in insulin or C-peptide concentrations (all p > 0.4). Viewing food pictures did not affect total calorie intake during the buffet (all p > 0.5) and snack consumption (all p > 0.4). Concentrations of ghrelin, adrenocorticotropic hormone (ACTH), cortisol, and glucagon also remained unaffected (all p > 0.08). These data indicate that preprandial processing of food cues curbs postprandial blood glucose excursions, without immediately affecting eating behavior in normal-weight and obese men. Findings indicate that exposure to food cues does not acutely trigger calorie overconsumption but rather improves the glucoregulatory response to food intake. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Food combination based on a pre-hispanic Mexican diet decreases metabolic and cognitive abnormalities and gut microbiota dysbiosis caused by a sucrose-enriched high-fat diet in rats.

    Science.gov (United States)

    Avila-Nava, Azalia; Noriega, Lilia G; Tovar, Armando R; Granados, Omar; Perez-Cruz, Claudia; Pedraza-Chaverri, José; Torres, Nimbe

    2017-01-01

    There is few information about the possible health effects of a food combination based on a pre-hispanic Mexican diet (PMD). This diet rich in fiber, polyphenols, a healthy ratio of omega 6/omega 3 fatty acids, and vegetable protein could improve carbohydrate and lipid metabolism, gut microbiota and cognitive function. We examined the effect of a PMD in a sucrose enriched high-fat model. The PMD contains corn, beans, tomato, nopal, chia and pumpkin seeds in dehydrated form. Following induction of obesity, rats were fed PMD. PMD consumption decreased glucose intolerance, body weight gain, serum and liver triglycerides and leptin. In addition, PMD decreased the size of the adipocytes, and increased the protein abundance of UCP-1, PPAR-α, PGC1-α and Tbx-1 in white adipose tissue. Finally, the PMD significant decreased hepatic levels of ROS, oxidized proteins and GSSG/GSH ratio and an increase in the relative abundance of Bifidobacteria and the improvement of cognitive function. Consumption of a PMD decreased the glucose intolerance and the biochemical abnormalities caused by the obesity by increasing the abundance of proteins involved in fatty acid oxidation, decreasing the oxidative stress and modifying the gut microbiota. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Roles of sex hormones on the regulation of leptin secretion in pregnant golden hamster

    International Nuclear Information System (INIS)

    Wang Cheng; Yang Liguo

    2003-01-01

    Objective: To investigate the effect of sex hormones on the secretion of leptin and the causative factor of the gestational leptin spike in the golden hamster. Methods: Three months old female golden hamster were used as animal model. As a source of high level estradiol and progesterone, silicane rubber tubes impregnates with estradiol and progesterone were prepared and their bioactivity were determined. Antisera against estradiol and progesterone were prepared and activity tested to be used, for the elimination of the effects of endogenous hormones on leptin secretion in the subsequent experiments. Biological activity of the antiserum was determined by evaluating effects of these antisera on the weight of uterus or ovary. Groups of pregnant animals were ovariectomied during day 11 of pregnancy to explore the effect of the gonad on the secretion of leptin. Groups of virgin animals were ovariectomied and the silicone rubber tubes containing estradiol and progesterone were implanted to determine the effect of high-level estradiol and progesterone on the secretion of leptin in vivo. Results: Plasma concentration of leptin decreased and the gestational leptin profile disappeared with absence of the secretion spike on day 12 after ovariectomy on the day 11 of pregnancy. Injections of antiserum against estradiol or progesterone had no significant effect on the plasma concentration of leptin. Leptin level significantly decreased after ovariectomy in the virgin golden hamsters (p < 0.05). Implantation of silicone rubber tubes of estradiol or progesterone after ovariectomy could not restore leptin levels, but implantation of tubes containing both estradiol and progesterone could prevent the decrease of leptin levels. Conclusion: Our results suggested that sex hormones had important regulatory effect on the secretion of leptin. Estradiol plus progesterone had stimulatory effects on the secretion of leptin in vivo. High estradiol and progesterone levels during pregnancy was

  3. Acute insulin-induced elevations of circulating leptin and feeding inhibition in lean but not obese rats.

    Science.gov (United States)

    Singh, Kimberly A; Boozer, Carol N; Vasselli, Joseph R

    2005-08-01

    Insulin has been shown to stimulate leptin mRNA expression acutely in rat adipose tissue, but its short-term effects on circulating leptin levels, and subsequent feeding behavior, have not been well described. We used 11-mo-old female selectively bred obesity-resistant (OR) and obesity-prone (OP) Sprague-Dawley rats maintained on laboratory chow to investigate this question. At testing, body weights and basal leptin levels of the OP rats were significantly elevated compared with the OR rats. In the 3-h fasted state, injection of 2.0 U insulin/kg ip resulted in significant elevations of plasma leptin at 4 h postinjection in both OP and OR groups (hour 4, +2.50 and +5.98 ng/ml, respectively). In separate feeding tests with the same groups, intake of laboratory chow pellets was significantly inhibited during hours 2-4 after 2.0 U/kg of insulin in the OR (-80.1%, P < 0.05), but not in the OP group, compared with intake after saline injections. In feeding tests with palatable moderately high-fat pellets after 2.0 and 3.0 U insulin/kg ip, significant decreases between hours 2 and 4 in intake were seen in the OR group only (-41.0 and -68.3%, respectively). Thus feeding inhibition coincides with insulin-induced elevations of plasma leptin in lean but not obese Sprague-Dawley rats. Our data suggest that elevations of leptin within the physiological range may contribute to short-term inhibition of food intake in rats and that this process may be stimulated by feeding-related insulin release.

  4. 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

  5. Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes

    OpenAIRE

    Marie Kokolski; Francis J. Ebling; James R. Henstock; Susan I. Anderson

    2017-01-01

    The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters (Phodopus sungorus) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity...

  6. Leptin and psychiatry

    African Journals Online (AJOL)

    QuickSilver

    and functions as a metabolic and neuro-endocrine hormone. Leptin has been shown to .... a study of 36 patients, Hinze Selch et al concluded that weight gain induced by .... European Journal ... and its encoded protein in Rodents: Impact of nutrition and obe- sity. Journal ... Psychology Annals 1989:19;488–493. 15. Elke D.

  7. 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

  8. Room Service Improves Nutritional Intake and Increases Patient Satisfaction While Decreasing Food Waste and Cost.

    Science.gov (United States)

    McCray, Sally; Maunder, Kirsty; Krikowa, Renee; MacKenzie-Shalders, Kristen

    2018-02-01

    .005) and protein (52 g/day vs 66 g/day, P=0.003) intake, as well as energy and protein intake as a percentage of requirements (63% vs 75%; P=0.024 and 65% vs 85%; P=0.011, respectively). Total mean plate waste decreased from 29% (traditional foodservice model) to 12% (room service) (P<0.001). Patient satisfaction ratings indicated improvement with room service across all Press Ganey meal scores: 68th to 86th percentile overall; 64th to 95th percentile for "quality of food"; and 60th to 99th percentile for "flavor of food." Evaluated during comparable times of the year, patient meal costs decreased by 15% with room service. A patient-centered foodservice model, such as room service, can improve patient nutritional intake and enhance patient satisfaction in a budget constrained health care environment. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  9. Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc.

    Science.gov (United States)

    Baltaci, Abdulkerim Kasım; Mogulkoc, Rasim

    2017-06-01

    Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT 3 , FT 4 , TT 3 , and TT 4 ) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.

  10. Dioxins and dioxin-like compounds in the food supply: strategies to decrease exposure

    National Research Council Canada - National Science Library

    Committee on the Implications of Dioxin in the Food Supply, National Research Council

    2003-01-01

    .... People are exposed to these unintentional environmental contaminants primarily through the food supply, although at low levels, particularly by eating animal fat in meat, dairy products, and fish...

  11. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons.

    Science.gov (United States)

    Mounien, Lourdes; Marty, Nell; Tarussio, David; Metref, Salima; Genoux, David; Preitner, Frédéric; Foretz, Marc; Thorens, Bernard

    2010-06-01

    The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-d-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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…

  14. 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

  15. Focusing on food during lunch enhances lunch memory and decreases later snack intake.

    Science.gov (United States)

    Higgs, Suzanne; Donohoe, Jessica E

    2011-08-01

    We investigated whether eating lunch mindfully, in contrast to eating with distractions or no particular focus, reduces later snack intake and if this is related to a measure of meal memory. The design was between-subjects with three conditions. Twenty-nine female undergraduate students either ate a fixed lunch while (1) focusing on the sensory characteristics of the food as they ate (food focus group), (2) reading a newspaper article about food (food thoughts control group) or (3) in the absence of any secondary task (neutral control group). Cookie intake later that afternoon was measured as well as rated vividness of memory of the lunch. Participants ate significantly fewer cookies in the food focus group than in both the food thoughts control group or the neutral control group. Rated appetite before the snack session was lower in the food focus group than in the other two groups and rated vividness of lunch memory was higher. Rated vividness of lunch memory was negatively correlated with snack intake. These results suggest that enhancing meal memory by paying attention to food while eating can reduce later intake and are consistent with the suggestion that memory plays an important role in appetite control. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults

    NARCIS (Netherlands)

    Andriessen, Charlotte; Christensen, Pia; Vestergaard Nielsen, Lone; Ritz, Christian; Astrup, Arne; Meinert Larsen, Thomas; Martinez, J.A.; Saris, Wim H.M.; Baak, van Marleen A.; Papadaki, Angeliki; Kunesova, Marie; Jebb, Susan; Blundell, John; Lawton, Clare; Raben, Anne

    2018-01-01

    People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy,

  17. Leptin, soluble leptin receptor, and free leptin index in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Elena N. Smirnova

    2017-06-01

    Full Text Available Aim. To assess the levels of leptin, its soluble receptor, and index of the formation of free leptin in metabolic syndrome (MS. Materials and methods. The study included 110 individuals with obesity and overweight. The group 1 consisted of 70 patients with MS (IDF, 2005, the average body mass index (BMI 38.4 ± 4.4 kg/m2, aged 48.2 ± 2.4 years, with arterial hypertension (AH 1–2 degree, without regular antihypertensive therapy. Group 2 – "healthy" obesity accounted for 40 patients aged 38.4 ± 6.2 years, BMI 36.0 ± 5.5 kg/m2 without hypertension and metabolic disorders. Group 3 consisted of 30 healthy persons, BMI 27.1 ± 1.3 kg/m2. All patients were evaluated for insulin, HOMA index, leptin, leptin receptor, leptin free index (calculated as the ratio of leptin (ng/ml to the leptin receptor (ng/ml, multiplied by 100. Results: In patients with MS as compared to other two groups there were higher levels of HOMA IR index, leptin and free leptin index. Values of leptin receptor in groups 1 and 2 did not differ significantly and were lower than in healthy persons. The free leptin index was significantly higher in MS group relative to the group 2 and 15 times higher than in the healthy individuals. Free leptin index correlated with values of BMI (R = 0.32; p = 0.02, blood pressure (R = 0.3; p = 0.04, uric acid (R = 0.27; p = 0.04, triglycerides (R = 0.42; p = 0.02, index HOMA-IR (R = 0.45; p = 0.02. Conclusions: Reduction of soluble leptin receptor, depending on the degree of abdominal obesity, may cause progression of leptin resistance in patients with MS. The levels of leptin and soluble leptin receptor appears to have dramatical gender differences. Calculation of free leptin index should be used for the objective evaluation of leptin resistance, regardless of gender, degree of obesity, and other metabolic parameters.

  18. Bis(tributyltin)oxide (TBTO) decreases the food allergic response against peanut and ovalbumin in Brown Norway rats

    International Nuclear Information System (INIS)

    Jonge, Jonathan D. de; Ezendam, Janine; Knippels, Leon M.J.; Odink, Jennie; Pourier, Milanthy S.; Penninks, Andre H.; Pieters, Raymond; Loveren, Henk van

    2007-01-01

    Other factors than the allergen itself may be of importance in the development of food allergy. This report describes the influence of the immunosuppressive compound bis(tributyltin)oxide (TBTO), present in the food chain, on the development of food allergy to peanut or ovalbumin in Brown Norway (BN) rats. To study these effects BN rats were sensitized to either 1 or 10 mg peanut or ovalbumin by daily oral gavage and the TBTO-groups were fed a diet containing 80 mg TBTO per kg diet. Co-exposure to TBTO not only resulted in decreased general immunologic parameters such as weights of mesenteric lymph nodes and Peyer's patches, lymphocyte proliferation rates in splenocytes, but also on allergic parameters. In the peanut allergen-model TBTO decreased allergen-specific Th2 cytokine production by spleen cells, number of eosinophilic and basophilic granulocytes in the blood and production of mast cell protease II after oral food challenge. In the ovalbumin allergen-model TBTO decreased the number of eosinophilic and basophilic granulocytes, allergen-specific IgE and production of mast cell protease II after oral food challenge. The data imply that in the process of risk assessment of food allergy attention should be given to immunomodulating compounds present in the diet

  19. Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring

    OpenAIRE

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Pontiggia, Laura; D���mello, Anil P

    2016-01-01

    The effects of perinatal nutrition on offspring physiology have mostly been examined in young adult animals. Aging constitutes a risk factor for the progressive loss of metabolic flexibility and development of disease. Few studies have examined whether the phenotype programmed by perinatal nutrition persists in aging offspring. Persistence of detrimental phenotypes and their accumulative metabolic effects are important for disease causality. This study determined the effects of maternal prote...

  20. Adiponectin receptor 2 is regulated by nutritional status, leptin and pregnancy in a tissue-specific manner.

    Science.gov (United States)

    González, Carmen Ruth; Caminos, Jorge Eduardo; Gallego, Rosalía; Tovar, Sulay; Vázquez, María Jesús; Garcés, María Fernanda; Lopez, Miguel; García-Caballero, Tomás; Tena-Sempere, Manuel; Nogueiras, Rubén; Diéguez, Carlos

    2010-01-12

    The aim of the present work was to study the regulation of circulating adiponectin levels and the expression of adiponectin receptor 2 (Adipo-R2) in several rat tissues in relation to fasting, leptin challenge, pregnancy, and chronic undernutrition. Using real-time PCR, we found Adipo-R2 mRNA expression in the liver, stomach, white and brown adipose tissues (WAT and BAT) of adult rats. Immunohistochemical studies confirmed protein expression in the same tissues. Adipo-R2 mRNA levels were decreased in liver after fasting, with no changes in the other tissues. Leptin decreased Adipo-R2 expression in liver and stomach, but increased its expression in WAT and BAT. Chronic caloric restriction in normal rats increased Adipo-R2 gene expression in stomach, while it decreased hepatic Adipo-R2 levels in pregnant rats. Using radioimmunoassay, we found that plasma adiponectin levels were diminished by fasting and leptin. Conversely, circulating adiponectin was increased in food-restricted rats, whereas its levels decreased in food-restricted pregnant rats by the end of gestation. In conclusion our findings provide the first evidence that (a) Adipo-R2 mRNA is regulated in a tissue-specific manner by fasting, but leptin is not responsible for those changes; (b) chronic caloric restriction in normal and pregnant rats also regulate Adipo-R2 mRNA in a tissue-specific manner; and (c) Adipo-R2 mRNA does not show a clear correlation with plasma adiponectin levels.

  1. 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)

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. The role of leptin in nutritional status and reproductive function.

    Science.gov (United States)

    Keisler, D H; Daniel, J A; Morrison, C D

    1999-01-01

    Infertility associated with suboptimal nutrition is a major concern among livestock producers. Undernourished prepubertal animals will not enter puberty until they are well fed; similarly, adult, normally cyclic females will stop cycling when faced with extreme undernutrition. Work in our laboratory has focused on how body fat (or adiposity) of an animal can communicate to the brain and regulate reproductive competence. In 1994, the discovery in rodents of the obese (ob) gene product leptin, secreted as a hormone from adipocytes, provided a unique opportunity to understand and hence regulate whole body compositional changes. There is now evidence that similar mechanisms are functioning in livestock species in which food intake, body composition, and reproductive performance are of considerable economic importance. Leptin has been reported to be a potent regulator of food intake and reproduction in rodents. There is evidence indicating that at least some of the effects of leptin occur through receptor-mediated regulation of the hypothalamic protein neuropeptide Y (NPY). NPY is a potent stimulator of food intake, is present at high concentrations in feed-restricted cattle and ewes, and is an inhibitor of LH secretion in these livestock species. In our investigations in sheep, we have cloned a partial cDNA corresponding to the ovine long-form leptin receptor, presumably the only fully active form, and have localized the long-form leptin receptor in the ventromedial and arcuate nuclei of the hypothalamus. Leptin receptor mRNA expression was colocalized with NPY mRNA-containing cell bodies in those regions. We have also determined that hypothalamic leptin receptor expression is greater in feed-restricted ewes than in well-fed ewes. These observations provide a foundation for future investigations into the nutritional modulators of reproduction in livestock.

  5. Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes.

    Science.gov (United States)

    Kokolski, Marie; Ebling, Francis J; Henstock, James R; Anderson, Susan I

    2017-01-01

    The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters ( Phodopus sungorus ) have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD)-induced winter state. In summer long day (LD) photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin's effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR). Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD) or high leptin (LD) states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early life and

  6. [Leptin: aspects on energetic balance, physical exercise and athletic amenorhea].

    Science.gov (United States)

    Ribeiro, Sandra Maria Lima; dos Santos, Zirlene Adriana; da Silva, Renata Juliana; Louzada, Eliana; Donato, José; Tirapegui, Julio

    2007-02-01

    The aim of this manuscript was to review the knowledge about leptin, detailing its relationship with energetic intake and physical activity. Leptin is an adipocyte hormone, recognized mainly for its putative role in control of energy expenditure, food intake, body weight and reproductive function. Leptin has still important peripheral actions, including its role on the ovarian tissue. The intracellular signaling mechanisms are recognized in hypothalamus, but in peripheral tissue are not fully understood. The exercise, when practiced by women, if not appropriately planned according to food intake, can modify the leptin release. When energy imbalances induced by exercise and/or deficient food ingestion occurs, low leptin levels are observed, leading to a reduction in GnRH (gonadotropin-release hormone), in LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in pituitary, and consequently a minor release of ovarian estrogens. This process is named hypothalamic amenorrhea, and has repercussions in the woman's health. In this perspective, it is important to emphasize the need to evaluate the energy expenditure from exercise and to formulate adequate alimentary plans to these individuals.

  7. Induction of pulsatile secretion of leptin in horses following thyroidectomy.

    Science.gov (United States)

    Buff, Preston R; Messer, Nat T; Cogswell, Andria M; Wilson, David A; Johnson, Philip J; Keisler, Duane H; Ganjam, Venkataseshu K

    2007-02-01

    Endocrine characteristics of Quarter Horse-type mares were determined during a 68 h feed deprivation and again in the same mares following surgical thyroidectomy (THX). A crossover experimental design was implemented, in which mares received brome hay available ad libitum (FED) or were food deprived (RES) for 68 h. Blood samples were collected every 20 min for 48 h, beginning 20 h after the onset of food deprivation. Concentrations of triiodothyronine and thyroxine were undetectable post-THX. Plasma concentrations of thyrotropin were greater post-THX versus pre-THX (P<0 x 001). Plasma concentrations of leptin were greater in the THX FED group than in the THX RES group (P<0 x 01). The existence of leptin pulse secretion was found only in post-THX compared with the same horses pre-THX (P=0 x 02). We theorize that non-pulsatile secretion of leptin may have contributed to the survival of this species, as it evolved in the regions of seasonal availability of food. Lack of pulsatile secretion of leptin may contribute to the accumulation of energy stores by modulating leptin sensitivity.

  8. Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin - A Threat To Diabetes Phytotherapy.

    Science.gov (United States)

    Majumdar, Jayjeet; Chakraborty, Pratip; Mitra, Analava; Sarkar, Nirmal Kumar; Sarkar, Supriti

    2017-07-01

    Fenugreek ( Trigonella foenum graecum) , a medicinal herb with potent antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT (hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have important role in normal and type-1 diabetic subjects. FSE (confirmed to contain trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks. Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum levels of TRH, TSH (Thyroid stimulating hormone), fT 3 , fT 4 , insulin, leptin, glucose; thyroperoxidase activity and growth of thyroid gland, food intake, adiposity index were also studied FSE significantly down regulated prepro-TRH mRNA expression; decreased serum TRH, TSH, fT 3 , fT 4 levels, and regressed thyroid gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed control and diabetic rats. FSE decreased (psecretion, increased food intake and body weight in all FSE-fed rats. FSE improved insulin secretion, decreased glucose level but impaired HPT axis in diabetic rats, indicating insulin-independent central hypothyroidism. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal actions raises questions whether it can be safely used to treat diabetes and/or hyperthyroidism as was suggested by many workers. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Dioxins and dioxin-like compounds in the food supply: strategies to decrease exposure

    National Research Council Canada - National Science Library

    Committee on the Implications of Dioxin in the Food Supply; Food and Nutrition Board; Institute of Medicine; National Research Council

    2003-01-01

    .... While the amount of DLCs in the environment has declined since the late 1970s, the public continues to be concerned about the safety of the food supply and the potential adverse health effects of DLC...

  10. 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)

  11. 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...

  12. Regulation of Blood Pressure, Appetite, and Glucose by Leptin After Inactivation of Insulin Receptor Substrate 2 Signaling in the Entire Brain or in Proopiomelanocortin Neurons.

    Science.gov (United States)

    do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Freeman, Nathan J; Alsheik, Ammar J; Adi, Ahmad; Hall, John E

    2016-02-01

    Insulin receptor substrate 2 (IRS2) is one of the 3 major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake, and glucose regulation is unclear. We tested whether genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic, and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure and heart rate and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 μg/kg per minute) for 7 days. Compared with control IRS2(flox/flox) mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 versus 35±1 g and 3.6±0.5 versus 3.8±0.2 g per day) but higher mean arterial pressure (MAP) and heart rate (110±2 versus 102±2 mm Hg and 641±9 versus 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g per day), and had higher MAP and heart rate (108±2 mm Hg and 659±9 bpm) compared with control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2(flox/flox) and in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the central nervous system, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects. © 2015 American Heart Association, Inc.

  13. Electroacupuncture Reduces Weight Gain Induced by Rosiglitazone through PPARγ and Leptin Receptor in CNS

    Directory of Open Access Journals (Sweden)

    Xinyue Jing

    2016-01-01

    Full Text Available We investigate the effect of electroacupuncture (EA on protecting the weight gain side effect of rosiglitazone (RSG in type 2 diabetes mellitus (T2DM rats and its possible mechanism in central nervous system (CNS. Our study showed that RSG (5 mg/kg significantly increased the body weight and food intake of the T2DM rats. After six-week treatment with RSG combined with EA, body weight, food intake, and the ratio of IWAT to body weight decreased significantly, whereas the ratio of BAT to body weight increased markedly. HE staining indicated that the T2DM-RSG rats had increased size of adipocytes in their IWAT, but EA treatment reduced the size of adipocytes. EA effectively reduced the lipid contents without affecting the antidiabetic effect of RSG. Furthermore, we noticed that the expression of PPARγ gene in hypothalamus was reduced by EA, while the expressions of leptin receptor and signal transducer and activator of transcription 3 (STAT3 were increased. Our results suggest that EA is an effective approach for inhibiting weight gain in T2DM rats treated by RSG. The possible mechanism might be through increased levels of leptin receptor and STAT3 and decreased PPARγ expression, by which food intake of the rats was reduced and RSG-induced weight gain was inhibited.

  14. Sida rhomboidea. Roxb leaf extract down-regulates expression of PPARγ2 and leptin genes in high fat diet fed C57BL/6J Mice and retards in vitro 3T3L1 pre-adipocyte differentiation.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Ramani, Umed V; Devkar, Ranjitsinh V; Ramachandran, A V

    2011-01-01

    Sida rhomboidea. Roxb leaf extract (SRLE) is being used by the populace of North-East India to alleviate symptoms of diabetes and obesity. We have previously reported its hypolipidemic and anti-diabetic properties. In this study, we report the effect of SRLE on (i) in vivo modulation of genes controlling high fat diet (HFD) induced obesity and (ii) in vitro 3T3L1 pre-adipocyte differentiation and leptin release. Supplementation with SRLE significantly prevented HFD induced increment in bodyweight, plasma lipids and leptin, visceral adiposity and adipocyte hypertrophy. Also, SRLE supplementation reduced food intake, down regulated PPARγ2, SREBP1c, FAS and LEP expressions and up-regulated CPT-1 in epididymal adipose tissue compared to obese mice. In vitro adipogenesis of 3T3L1 pre-adipocytes was significantly retarded in the presence of SRLE extract. Also decreased triglyceride accumulation, leptin release and glyceraldehyde-3-Phosphate dehydrogenase activity along with higher glycerol release without significant alteration of viability of 3T3L1 pre-adipocytes, was recorded. Our findings suggest that prevention of HFD induced visceral adiposity is primarily by down regulation of PPARγ2 and leptin gene expression coupled with attenuation of food intake in C57BL/6J mice. SRLE induced prevention of pre-adipocytes differentiation, and leptin release further substantiated these findings and scientifically validates the potential application of SRLE as a therapeutic agent against obesity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Erkasap, N.; Ozkurt, M. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Erkasap, S.; Yasar, F. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uzuner, K. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Ihtiyar, E. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uslu, S.; Kara, M. [Department of Biochemistry, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Bolluk, O. [Department of Biostatistics, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey)

    2013-03-19

    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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    N. Erkasap

    Full Text Available 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.

  18. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  19. Leptin and reproduction: a review.

    Science.gov (United States)

    Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

    2002-03-01

    To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. A MEDLINE computer search was performed to identify relevant articles. Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

  20. Ability of GLP-1 to decrease food intake is dependent on nutritional status.

    Science.gov (United States)

    Ronveaux, Charlotte C; de Lartigue, Guillaume; Raybould, Helen E

    2014-08-01

    Gut-derived glucagon like peptide-1 (GLP-1) acts in the postprandial period to stimulate insulin secretion and inhibit gastrointestinal motor and secretory function; whether endogenous peripheral GLP-1 inhibits food intake is less clear. We hypothesized that GLP-1 inhibits food intake in the fed, but not fasted, state. There is evidence that GLP-1 acts via stimulation of vagal afferent neurons (VAN); we further hypothesized that the satiating effects of endogenous GLP-1 in the postprandial period is determined either by a change in GLP-1 receptor (GLP-1R) expression or localization to different cellular compartments in VAN. Food intake was recorded following administration of GLP-1 (50μg/kg or 100μg/kg) or saline (IP) in Wistar rats fasted for 18h or fasted then re-fed with 3g chow. GLP-1R protein expression and localization on VAN were determined by immunocytochemistry and immunoblots in animals fasted for 18h or fasted then re-fed for 40min. GLP-1R mRNA level was detected in animals fasted for 18h or fasted and re-fed ad libitum for 2h. GLP-1 (100μg/kg) significantly reduced 40min food intake by 38% in re-fed but not fasted rats (pfasted rats. However, GLP-1R localization to the plasma membrane was significantly increased in VAN by feeding. Feeding changes the ability of peripheral GLP-1 to inhibit food intake. GLP-1Rs are trafficked to the plasma membrane in response to a meal. GLP-1 may play a role in regulating food intake in the postprandial period. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Photoperiod-Induced Increases in Bone Mineral Apposition Rate in Siberian Hamsters and the Involvement of Seasonal Leptin Changes

    Directory of Open Access Journals (Sweden)

    Marie Kokolski

    2017-12-01

    Full Text Available The adipokine leptin regulates energy balance, appetite, and reproductive maturation. Leptin also acts on bone growth and remodeling, but both osteogenic and anti-osteogenic effects have been reported depending on experimental conditions. Siberian hamsters (Phodopus sungorus have natural variation in circulating leptin concentrations, where serum leptin is significantly decreased during the short day (SD-induced winter state. In summer long day (LD photoperiods, appetite and body adiposity increase with associated central leptin insensitivity. This natural change in leptin secretion was exploited to investigate leptin’s effect on bone growth. Hamsters were injected with calcium-chelating fluorescent dyes to measure bone mineral apposition rate (MAR. Measurements were initially obtained from 5-week and 6-month-old animals maintained in low leptin (SD or high leptin (LD states. A further study investigated effects of chronic administration of recombinant mouse leptin to hamsters housed in SD and LD conditions; growth plate thickness and bone density were also assessed. As expected, a reduction in body mass was seen in hamsters exposed to SD, confirming the phenotype change in all studies. Serum leptin concentrations were significantly reduced in SD animals in all studies. MAR was reproducibly and significantly increased in the femurs of SD animals in all studies. Vitamin D and growth plate thickness were significantly increased in SD animals at 6 months. No effect on bone density was observed in any study. Taken together these data suggest that bone growth is associated with the low leptin, winter, lean state. In leptin-treated animals, there was a significant interaction effect of leptin and photoperiod. In comparison to their vehicle counterparts, SD animals had decreased and LD animals had increased MAR, which was not apparent prior to leptin administration. In conclusion, increased MAR was associated with low serum leptin levels in early

  2. Intraduodenal infusion of a combination of tastants decreases food intake in humans

    NARCIS (Netherlands)

    Avesaat, M. van; Troost, F.J.; Ripken, D.; Peters, J.; Hendriks, H.F.J.; Masclee, A.A.M.

    2015-01-01

    Background: Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. Objective: This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and

  3. Intraduodenal infusion of a combination of tastants decreases food intake in humans

    NARCIS (Netherlands)

    Avesaat, Van Mark; Troost, F.J.; Ripken, Dina; Peters, Jelmer; Hendriks, H.F.J.; Masclee, A.A.M.

    2015-01-01

    Background: Taste receptors are expressed not only in taste buds but also in the gastrointestinal tract. It has been hypothesized that these receptors may play a role in satiety and food intake. Objective: This study investigated the effect of intraduodenal tastant infusions (bitter, sweet, and

  4. Effects of Metformin on Serum Levels of Secreted Klotho and Leptin in PCOS Women

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

    Science.gov (United States)

    Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2017-05-01

    Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

  7. Characterization of Leptin Intracellular Trafficking

    Directory of Open Access Journals (Sweden)

    E Walum

    2009-12-01

    Full Text Available Leptin is produced by adipose tissue, and its concentration in plasma is related to the amount of fat in the body. The leptin receptor (OBR is a member of the class I cytokine receptor family and several different isoforms, produced by alternative mRNA splicing are found in many tissues, including the hypothalamus. The two predominant isoforms includes a long form (OBRl with an intracellular domain of 303 amino acids and a shorter form (OBRs with an intracellular domain of 34 amino acids. Since OBRl is mainly expressed in the hypotalamus, it has been suggested to be the main signalling form. The peripheral production of leptin by adipocyte tissue and its effects as a signal of satiety in the central nervous system imply that leptin gains access to regions of the brain regulating in energy balance by crossing the blood-brain barrier. In an attempt to characterize the intracellular transport of leptin, we have followed binding internalization and degradation of leptin in HEK293 cells. We have also monitored the intracellular transport pathway of fluorescent conjugated leptin in HEK293 cells. Phenylarsine oxide, a general inhibitor of endocytosis, as well as incubation at mild hypertonic conditions, prevented the uptake of leptin, confirming a receptor-mediated internalization process. When internalized, 125I-leptin was rapidly accumulated inside the cells and reached a maximum after 10 min. After 70 minutes about 40-50% of total counts in each time point were found in the medium as TCA-soluble material. Leptin sorting, at the level of early endosomes, did not seem to involve recycling endosomes, since FITC-leptin was sorted from Cy3- transferrin containing compartments at 37°C. At 45 minutes of continuos internalization, FITC-leptin appeared mainly accumulated in late endocytic structures colocalizing with internalized rhodamine coupled epidermial growth factor (EGF and the lysosomal marker protein lamp-1. The transport of leptin was also shown

  8. Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner.

    Science.gov (United States)

    Folgueira, C; Sanchez-Rebordelo, E; Barja-Fernandez, S; Leis, R; Tovar, S; Casanueva, F F; Dieguez, C; Nogueiras, R; Seoane, L M

    2016-03-01

    Uroguanylin (UGN) is a 16 amino acid peptide produced mainly by intestinal epithelial cells. Nutrients intake increases circulating levels of prouroguanylin that is processed and converted to UGN to activate the guanylyl cyclase 2C receptor (GUCY2C). Given that the UGN-GUCY2C system has been proposed as a novel gut-brain endocrine axis regulating energy balance, the aim of the present study was to investigate the regulation of UGN protein levels in duodenum and circulating levels in lean and obese mice under different nutritional conditions and its potential interaction with leptin. Swiss, C57BL/6 wild-type and ob/ob male adult mice under different nutritional conditions were used: fed ad libitum standard diet (control); 48 h fasting (fasted); 48 h fasting followed by 24 h of feeding (refed); and fed high-fat diet (45 %) during 10 weeks. In addition, peripheral leptin administration was performed. Intestinal uroguanylin expression was studied by Western blot analysis; plasma levels were measured by ELISA. Food deprivation significantly reduced plasma UGN levels, which were correlated with the lower protein levels of UGN in duodenum. These effects were reverted after refeeding and leptin challenge. Consistently, in ob/ob mice UGN expression was decreased, whereas leptin treatment up-regulated UGN levels in duodenum in these genetically modified mice compared to WT. Diet-induced obese mice displayed increased UGN levels in intestine and plasma in comparison with lean mice. Our findings suggest that UGN levels are correlated with energy balance status and that the regulation of UGN by nutritional status is leptin-dependent.

  9. Variations in leptin, nesfatin-1 and irisin levels induced by aerobic exercise in young trained and untrained male subjects

    Directory of Open Access Journals (Sweden)

    Sermin Algul

    2017-12-01

    Full Text Available The aims of this study were to investigate the impacts of acute aerobic exercise on circulating levels of hormones associated with energy metabolism, namely leptin, nesfatin-1 and irisin, in trained and untrained male subjects and to determine whether the timing of the exercise (i.e. morning or night amplified these impacts. Thirty trained (19.2±0.7 years and 30 untrained (19.5±0.6 years male subjects performed two aerobic running exercises (3 days between tests to 64-76% of the subjects’ maximal heart rate for about 30 min. Pre- and post-exercise venous blood samples were taken and analysed for leptin, nesfatin-1 and irisin using enzyme-linked immunosorbent assay (ELISA. Paired samples and independent samples t-tests were used to analyse data. Irisin levels increased in all the subjects (p<0.001. In both groups, nesfatin-1 levels increased significantly after the night-time exercise (p<0.05. Importantly, leptin and nesfatin-1 levels varied among the trained and untrained groups: Both leptin and nesfatin-1 levels increased in 4 (13% and 12 (40% subjects, respectively, after the morning exercises, and they increased in 9 (30% and 10 (33% subjects, respectively, after the night-time exercise. They decreased in 5 (16% and 7 (23% subjects, respectively, after the morning exercise and in 6 (20% and 3 (10% subjects, respectively, after the night-time exercise. Exercise may result in increased energy consumption by altering irisin levels. However, due to variations among individuals, increasing leptin and nesfatin-1 levels by reducing food intake may not be applicable.

  10. Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

    Science.gov (United States)

    Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

    2008-07-01

    States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

  11. Dieting in bulimia nervosa is associated with increased food restriction and psychopathology but decreased binge eating.

    Science.gov (United States)

    Lowe, Michael R; Witt, Ashley A; Grossman, Stephanie L

    2013-08-01

    The cognitive behavioral model of bulimia nervosa (BN) suggests that dieting is central to the maintenance of binge eating. However, correlational and experimental studies suggest that additional clarification is needed about the nature of this relationship. Dieting, weight, eating disorder psychopathology, and depression were assessed at admission among 166 patients with BN presenting for residential treatment. As in past research, a significant fraction (43%) of patients with BN reported not currently dieting. A comparison of weight loss dieters and non-dieters found greater food restriction and eating disorder psychopathology among weight loss dieters. However, dieters reported less frequent binge eating. There were no significant group differences in depression. Results suggest that 1) while many individuals with BN are attempting to restrict their food intake, the goal of losing weight fundamentally alters the effect of such restriction on binge eating, and 2) treatment may benefit from helping patients to establish a healthier approach to achieving long-term weight stability. © 2013.

  12. Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats.

    Science.gov (United States)

    Ortolani, D; Oyama, L M; Ferrari, E M; Melo, L L; Spadari-Bratfisch, R C

    2011-07-06

    It has been suggested that access to high caloric food attenuates stress response. The present paper investigates whether access to commercial chow enriched with glucose and fat, here referred to as comfort food alters behavioral, metabolic, and hormonal parameters of rats submitted to three daily sessions of foot-shock stress. Food intake, anxiety-like behaviors, and serum levels of insulin, leptin, corticosterone, glucose and triglycerides were determined. The rats submitted to stress decreased the intake of commercial chow, but kept unaltered the intake of comfort food. During the elevated plus maze (EPM) test, stressed rats increased the number of head dipping, entries into the open arms, as well as the time spent there, and decreased the number of stretched-attend posture and risk assessment. These effects of stress were independent of the type of food consumed. Non-stressed rats ingesting comfort food decreased risk assessment as well. Stress and comfort food increased time spent in the center of the open field and delayed the first crossing to a new quadrant. Stress increased the plasma level of glucose and insulin, and reduced triglycerides, although consumption of comfort food increases glucose, triglyceride and leptin levels; no effect on leptin level was associated to stress. The stress induced increase in serum corticosterone was attenuated when rats had access to comfort food. It was concluded that foot-shock stress has an anorexigenic effect that is independent of leptin and prevented upon access to comfort food. Foot-shock stress also has an anxiolytic effect that is potentiated by the ingestion of comfort food and that is evidenced by both EPM and open field tests. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Single Nucleotide Polymorphisms in the Leptin-a Gene and Associations with Growth Traits in the Orange-Spotted Grouper (Epinephelus coioides

    Directory of Open Access Journals (Sweden)

    Haoran Lin

    2013-04-01

    Full Text Available Leptin is a multifunctional protein involved in processes such as body weight regulation, energy expenditure, fat metabolism, food intake, and appetite regulation. Duplicate leptin genes, leptin-a and leptin-b, were previously detected in the orange-spotted grouper. In this study, we cloned the full-length open reading frame (ORF of the leptin-a gene in the orange-spotted grouper, searched for polymorphisms, and performed association analyses between these polymorphisms and seven growth traits. Six polymorphisms, consisting of 2 SNPs in intron 1 (c.182T > G, c.183G > T and 4 SNPs in exon 2 (c.339C > G, c.345C > T, c.447G > A, c.531C > T, were identified and genotyped in 200 individuals. The c.182T > G and c.183G > T polymorphisms showed complete linkage and were analyzed together. Association analyses revealed that the c.182 + 183TG > GT polymorphism was significantly associated with body weight (BWT and body width (BWH, with the AB (TG/GT genotype showing positive effects on growth traits. Additionally, the SNP c.447G > A was significantly associated with BWT, BWH, overall length (OL, trunk width (TW, and head length (HL, with the GA genotype displaying positive effects on growth traits. The c.531C > T SNP showed a close association between the TT genotype and decreased growth. Our results demonstrate that several polymorphisms in the leptin-a gene are associated with growth traits and can be used for marker-assisted selection (MAS in orange-spotted grouper populations.

  14. Nurse's Desk: food bank-based outreach and screening to decrease unmet referral needs.

    Science.gov (United States)

    Larsson, Laura S; Kuster, Emilie

    2013-01-01

    The Nurse's Desk health screening project used the Intervention Wheel model to conduct outreach, screening, education, and referral for food bank clients (n = 506). Blood glucose, blood pressure, health care utilization, and unmet referral needs were assessed. Screening results identified 318 clients (62.8%) with 1 or more unmet referral needs, including 6 clients (3.16%) with capillary blood glucose more than 199 mg/dL and 132 (31.9%) with hypertension. Clients had higher-than-average systolic and diastolic blood pressures and undiagnosed diabetes than in the general population. A client-approved method for tracking completed referrals is needed for this potentially high-risk population.

  15. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

    Science.gov (United States)

    French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

    2017-06-08

    A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  16. 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

  17. Leptin: A biomarker for sleep disorders?

    OpenAIRE

    Pan, Weihong; Kastin, Abba J.

    2013-01-01

    Leptin, a pleiotropic protein hormone produced mainly by fat cells, regulates metabolic activity and many other physiological functions. The intrinsic circadian rhythm of blood leptin is modulated by gender, development, feeding, fasting, sleep, obesity, and endocrine disorders. Hyperleptinemia is implicated in leptin resistance. To determine the specificity and sensitivity of leptin concentrations in sleep disorders, we summarize here the alterations of leptin in four conditions in animal an...

  18. 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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  20. 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

  1. 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

  2. [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.

  3. 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.

  4. Taste bud leptin: sweet dampened at initiation site.

    Science.gov (United States)

    Travers, Susan P; Frank, Marion E

    2015-05-01

    The intriguing observation that leptin decreases sweet-evoked peripheral gustatory responses has aroused much interest (Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y. 2000. Leptin as a modulator of sweet taste sensitivities in mice. Proc Natl Acad Sci U S A. 97(20):11044-11049.) due to its implied importance in controlling appetite. The effects of this anorexic hormone, however, appear more conditional than originally believed. In this issue of Chemical Senses, a careful study by Glendinning and colleagues, find no effects of leptin on sweet-evoked chorda tympani responses, whereas an equally careful study by Meredith and colleagues, find decreased release of ATP and increased release of 5-HT from taste buds in response to sweet stimuli. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Correlation of the leptin

    DEFF Research Database (Denmark)

    Finucane, F; Luan, J; Wareham, N

    2009-01-01

    (M/I) from hyperinsulinaemic-euglycaemic clamp studies in 1,226 EGIR RISC participants. RESULTS: The LAR was highly correlated with HOMA-S in men (r = -0.58, p = 4.5 x 10(-33) and r = -0.65, p = 1.1 x 10(-66) within the Ely and EGIR RISC study cohorts, respectively) and in women (r = -0.51, p = 2.8 x...... 10(-36) and r = -0.61, p = 2.5 x 10(-73)). The LAR was also strongly correlated with the clamp M/I value (r = -0.52, p = 4.5 x 10(-38) and r = -0.47, p = 6.6 x 10(-40) in men and women, respectively), similar to correlations between HOMA-S and the M/I value. CONCLUSIONS/INTERPRETATION: The leptin...

  6. Curcuminoids Lower Plasma Leptin Concentrations: A Meta-analysis.

    Science.gov (United States)

    Atkin, Stephen L; Katsiki, Niki; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

    2017-12-01

    Curcumin is a naturally occurring polyphenol that has been suggested to improve several metabolic diseases. Leptin is an adipokine involved in metabolic status and appetite, with marked crosstalk with other systems. Available data suggest that curcumin may affect leptin levels; therefore, this meta-analysis was performed to evaluate this. A systematic review and meta-analysis were undertaken on all randomized controlled trials of curcumin studies that included the measurement of leptin. The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases. Quantitative data synthesis was performed by using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. A funnel plot, Begg's rank correlation, and Egger's weighted regression tests assessed the presence of publication bias. Four eligible articles comprising five treatment arms were selected for the meta-analysis. Meta-analysis showed a significant decrease in plasma leptin concentrations following curcumin treatment (standardized mean difference: -0.69, 95% confidence interval: -1.16, -0.23, p = 0.003; I 2  = 76.53%). There was no evidence of publication bias. This meta-analysis showed that curcumin supplementation is associated with a decrease in leptin levels that may be regarded as a potential mechanism for the metabolic effects of curcumin. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  7. A premeal snack of raisins decreases mealtime food intake more than grapes in young children.

    Science.gov (United States)

    Patel, Barkha P; Luhovyy, Bohdan; Mollard, Rebecca; Painter, James E; Anderson, G Harvey

    2013-04-01

    The effect of a premeal snack of grapes, raisins, or a mix of almonds and raisins, compared with a water control, on food intake (FI) was examined in 8- to 11-year-old normal-weight (15th to 85th percentile) children. Children randomly received 1 of 4 ad libitum (Experiment 1: 13 boys, 13 girls) or fixed-calorie (150 kcal; Experiment 2: 13 boys, 13 girls) treatments, followed by an ad libitum pizza meal 30 min later. Appetite was measured throughout the study, and FI was measured at 30 min. The ad libitum consumption (Experiment 1) of raisins reduced pizza intake (p snack (15%). Cumulative energy intake (in kcal: snack + pizza) was lower after water and raisins than after either grapes or the mixed snack (p snack (Experiment 2), raisins reduced pizza intake, compared with water (∼11%, p = 0.005), and resulted in a cumulative intake similar to water; however, both grapes and the mixed snack resulted in higher cumulative intakes (p snacks (p snack (p consumption of a premeal snack of raisins, but not grapes or a mix of raisins and almonds, reduces meal-time energy intake and does not lead to increased cumulative energy intake in children.

  8. A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

    Directory of Open Access Journals (Sweden)

    William W. French

    2017-06-01

    Full Text Available A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa and lean control (Fa/fa rats were randomly assigned to either a high-protein (40% energy or moderate-protein (20% energy diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8, lean 40% protein (L40; n = 10, obese 20% protein (O20; n = 8, and obese 40% protein (O40; n = 10. At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05 compared to O20. O40 rats had lower liver weight (p < 0.05 compared to O20. However, O40 rats had higher orexin (p < 0.05 levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1 phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ mRNA expression compared to O20 (p < 0.05, with no difference in 5′ AMP-activated protein kinase (AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1, protein kinase B (Akt or p70 ribosomal S6 kinase (p70S6K phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

  9. Plasma leptin concentration in donkeys.

    Science.gov (United States)

    Díez, E; López, I; Pérez, C; Pineda, C; Aguilera-Tejero, E

    2012-01-01

    Donkeys appear to be more predisposed than large breed horses to suffer from hyperlipemia. The reason for that predisposition is unknown but anorexia is a consistent feature of the disease. Leptin, a protein synthesized in fat tissue, is one of the major inhibitors of appetite in mammals. We hypothesized that donkeys could have elevated plasma leptin concentrations compared to horses. Blood samples were obtained from 50 donkeys for measurement of leptin, triglycerides (TGs), glucose, and insulin. Glucose/insulin ratio, modified insulin to glucose ratio, and reciprocal of the square root of insulin were calculated. Based on their body condition score (BCS), donkeys were classified as lean (n = 18), normal (n = 16), or overweight (n = 16). The results were compared with reference values from our laboratory and with a group of horses (n = 25) used as an internal control. Values of both leptin and TGs in donkeys were above the horse reference range and also significantly higher than those of the control horses: leptin (11.2 ± 1.7 versus 5.8 ± 0.5 µg/L, p donkeys had leptin (19.3 ± 2.9 µg/L) and TG (1.3 ± 0.2 mmol/L) concentrations that were significantly (p donkeys. A significant positive correlation (p Donkeys have higher plasma leptin concentrations than horses and leptin is correlated with BCS.

  10. Leptin, An Adipokine With Central Importance in the Global Obesity Problem.

    Science.gov (United States)

    Mechanick, Jeffrey I; Zhao, Shan; Garvey, W Timothy

    2017-12-13

    Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

  11. 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.

  12. Hormonal, lifestyle, and dietary factors in relation to leptin among elderly men.

    Science.gov (United States)

    Lagiou, P; Signorello, L B; Mantzoros, C S; Trichopoulos, D; Hsieh, C C; Trichopoulou, A

    1999-01-01

    Leptin, the adipocyte-secreted protein product of the ob gene, has been strongly linked to obesity and is believed to play a role in the regulation of the reproductive system. This study examines the potential influence of lifestyle and dietary factors, as well as of other hormones, on serum levels of leptin. The authors studied a population of 48 healthy elderly Greek men. Sera from these men were analyzed for leptin, several steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1. The authors also utilized data from food frequency questionnaires and information on demographic, anthropometric, and lifestyle (cigarette smoking, alcohol and coffee drinking) factors. Using linear regression modeling, serum leptin levels were inversely associated with testosterone and positively associated with estradiol and dehydroepiandrosterone sulfate, after adjustment for the other hormones and body mass index (BMI). Leptin levels in men with a BMI >30 kg/m2 were 170% higher than in men with a BMI coffee drinking, or total energy intake, on the other. When total energy intake was separated into its three major components (carbohydrate, fat, and protein), it appeared that fat intake may have an isocalorically differential effect on serum leptin levels; one marginal quintile increase in fat intake corresponded to an 11% increase in leptin (95% CI 0-24%). Serum levels of leptin may be influenced by other endocrine factors, especially testosterone and estradiol, and may be positively associated with excess fat intake independently of obesity.

  13. Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control.

    Science.gov (United States)

    Soliman, Ashraf T; Omar, Magdi; Assem, Hala M; Nasr, Ibrahim S; Rizk, Mohamed M; El Matary, Wael; El Alaily, Rania K

    2002-03-01

    Although obesity is a frequent feature of type 2 diabetes mellitus (DM), many patients with type 1 DM are prone to high body mass index (BMI). We measured serum leptin concentrations in a cohort of children (n = 55) with type 1 diabetes mellitus (DM), as well as their anthropometric parameters including BMI, skin fold thickness at multiple sites, and midarm circumference. Glycemic control was assessed by blood glucose (BG) monitoring before meals, and measurement of glycated hemoglobin (HbA1c) and insulin dose/kg/d was recorded. Dietary evaluation and assessment of caloric intake (kg/d) was performed by an expert dietitian. In the newly diagnosed children (n = 10) before initiation of insulin therapy, circulating leptin concentration was significantly lower (1.1 +/- 0.8 ng/dL) versus 5 days after insulin therapy (1.45 +/- 0.7 ng/dL). The decreased leptin level appears to be related to insulinopenia in these patients. In 45 children with type 1 DM on conventional therapy (2 doses of insulin mixture (NPH and regular) subcutaneous (SC) before breakfast and dinner for more than 2 years), serum leptin concentration was significantly higher (2.15 +/- 1 ng/dL) compared with age-matched normal children (1.3 +/- 1 ng/dL). Diabetic children were further divided into 2 groups according to their HbA1c level: group 1 with HbA1C less than 7.5% (less than 2 SD above the mean for normal population) (n = 29) and group 2 with HbA1c greater than 7.5%. (greater than 2 SD above the mean for normal population) (n = 16). Patients with a higher HbA1c level (group 2) had a higher leptin concentration (2.3 +/- 0.8 ng/dL), higher BMI (17.8 +/- 1.7), and were receiving higher insulin dose/kg (0.92 +/- 0.2 U/kg/d) compared with group 1 (lower HbA1c) (1.78 +/- 0.8 ng/dL, 16.7 +/- 1.5, and 0.59 +/- 0.2 U/kg/d, respectively). Group 2 patients had a higher incidence of late morning hypoglycemia (9/29) versus group 1 patients (2/16). Analysis of dietary intake showed that patients with a higher Hb

  14. 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.

  15. Leptin-dependent neurotoxicity via induction of apoptosis in adult rat neural stem cells

    Directory of Open Access Journals (Sweden)

    Stéphanie eSEGURA

    2015-09-01

    Full Text Available Adipocyte-derived hormone leptin has been recently implicated in the control of neuronal plasticity. To explore whether modulation of adult neurogenesis may contribute to leptin control of neuronal plasticity, we used the neurosphere assay of neural stem cells derived from the adult rat subventricular zone (SVZ. Endogenous expression of specific leptin receptor (ObRb transcripts, as revealed by RT-PCR, is associated with activation of both ERK and STAT-3 pathways via phosphorylation of the critical ERK/STAT-3 amino acid residues upon addition of leptin to neurospheres. Furthermore, leptin triggered withdrawal of neural stem cells from the cell cycle as monitored by Ki67 labelling. This effect was blocked by pharmacological inhibition of ERK activation thus demonstrating that ERK mediates leptin effects on neural stem cell expansion. Leptin-dependent withdrawal of neural stem cells from the cell cycle was associated with increased apoptosis, as detected by TUNEL, which was preceded by cyclin D1 induction. Cyclin D1 was indeed extensively colocalized with TUNEL-positive apoptotic cells. Cyclin-D1 silencing by specific shRNA prevented leptin-induced decrease of the cell number per neurosphere thus pointing to the causal relationship between leptin actions on apoptosis and cyclin D1 induction. Leptin target cells in SVZ neurospheres were identified by double TUNEL/phenotypic marker immunocytofluorescence as differentiating neurons mostly. The inhibition of neural stem cell expansion via ERK/cyclin D1-triggered apoptosis defines novel biological action of leptin which may be involved in adiposity-dependent neurotoxicity.

  16. 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.

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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)

  20. 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.

  1. Decreasing food fussiness in children with obesity leads to greater weight loss in family-based treatment.

    Science.gov (United States)

    Hayes, Jacqueline F; Altman, Myra; Kolko, Rachel P; Balantekin, Katherine N; Holland, Jodi Cahill; Stein, Richard I; Saelens, Brian E; Welch, R Robinson; Perri, Michael G; Schechtman, Kenneth B; Epstein, Leonard H; Wilfley, Denise E

    2016-10-01

    Food fussiness (FF), or the frequent rejection of both familiar and unfamiliar foods, is common among children and, given its link to poor diet quality, may contribute to the onset and/or maintenance of childhood obesity. This study examined child FF in association with anthropometric variables and diet in children with overweight/obesity participating in family-based behavioral weight loss treatment (FBT). Change in FF was assessed in relation to FBT outcome, including whether change in diet quality mediated the relation between change in FF and change in child weight. Child (N = 170; age = 9.41 ± 1.23) height and weight were measured, and parents completed FF questionnaires and three 24-h recalls of child diet at baseline and post-treatment. Healthy Eating Index-2005 scores were calculated. At baseline, child FF was related to lower vegetable intake. Average child FF decreased from start to end of FBT. Greater decreases in FF were associated with greater reductions in child body mass index and improved overall diet quality. Overall, diet quality change through FBT mediated the relation between child FF change and child body mass index change. Children with high FF can benefit from FBT, and addressing FF may be important in childhood obesity treatment to maximize weight outcomes. © 2016 The Obesity Society.

  2. 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

  3. Genetics and physiology of leptin in periparturient dairy cows

    NARCIS (Netherlands)

    Liefers, S.C.; Veerkamp, R.F.; Pas, te M.F.W.; Chilliard, Y.; Lende, van der T.

    2005-01-01

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

  4. 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.

  5. Leptin promotor mutations affect leptin levels and performance traits in dairy cows

    NARCIS (Netherlands)

    Liefers, S.C.; Pas, te M.F.W.; Veerkamp, R.F.; Platje, M.; Delavaud, C.; Chilliard, Y.; Lende, van der T.

    2005-01-01

    Leptin concentrations in body fluids and tissues undergo dynamic changes during the periparturient period. Polymorphisms in the leptin gene have been shown to be associated with differences in leptin concentration during late pregnancy but not during lactation. As the promoter of leptin regulates

  6. Severe energy deficit upregulates leptin receptors, leptin signaling, and PTP1B in human skeletal muscle.

    Science.gov (United States)

    Perez-Suarez, Ismael; Ponce-González, Jesús Gustavo; de La Calle-Herrero, Jaime; Losa-Reyna, Jose; Martin-Rincon, Marcos; Morales-Alamo, David; Santana, Alfredo; Holmberg, Hans-Christer; Calbet, Jose A L

    2017-11-01

    In obesity, leptin receptors (OBR) and leptin signaling in skeletal muscle are downregulated. To determine whether OBR and leptin signaling are upregulated with a severe energy deficit, 15 overweight men were assessed before the intervention (PRE), after 4 days of caloric restriction (3.2 kcal·kg body wt -1 ·day -1 ) in combination with prolonged exercise (CRE; 8 h walking + 45 min single-arm cranking/day) to induce an energy deficit of ~5,500 kcal/day, and following 3 days of control diet (isoenergetic) and reduced exercise (CD). During CRE, the diet consisted solely of whey protein ( n = 8) or sucrose ( n = 7; 0.8 g·kg body wt -1 ·day -1 ). Muscle biopsies were obtained from the exercised and the nonexercised deltoid muscles and from the vastus lateralis. From PRE to CRE, serum glucose, insulin, and leptin were reduced. OBR expression was augmented in all examined muscles associated with increased maximal fat oxidation. Compared with PRE, after CD, phospho-Tyr 1141 OBR, phospho-Tyr 985 OBR, JAK2, and phospho-Tyr 1007/1008 JAK2 protein expression were increased in all muscles, whereas STAT3 and phospho-Tyr 705 STAT3 were increased only in the arms. The expression of protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle was increased by 18 and 45% after CRE and CD, respectively ( P < 0.05). Suppressor of cytokine signaling 3 (SOCS3) tended to increase in the legs and decrease in the arm muscles (ANOVA interaction: P < 0.05). Myosin heavy chain I isoform was associated with OBR protein expression ( r  = -0.75), phospho-Tyr 985 OBR ( r  = 0.88), and phospho-Tyr 705 STAT3/STAT3 ( r = 0.74). In summary, despite increased PTP1B expression, skeletal muscle OBR and signaling are upregulated by a severe energy deficit with greater response in the arm than in the legs likely due to SOCS3 upregulation in the leg muscles. NEW & NOTEWORTHY This study shows that the skeletal muscle leptin receptors and their corresponding signaling cascade are upregulated in

  7. Maternal serum leptin concentration in gestational diabetes

    Directory of Open Access Journals (Sweden)

    Sedigheh Soheilykhah

    2011-06-01

    Conclusion: Our data showed that serum leptin level was higher in GDM and had a positive correlation with insulin resistance. Our findings suggest that high leptin levels might be a risk factor for GDM and IGT in pregnant women.

  8. Metabolic Risk Susceptibility in Men Is Partially Related to Adiponectin/Leptin Ratio

    Directory of Open Access Journals (Sweden)

    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.

  9. 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)

  10. Renaissance of leptin for obesity therapy

    DEFF Research Database (Denmark)

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

    2016-01-01

    evident that leptin as a stand-alone therapy is not an effective approach, the potential for employing sensitising pharmacology to unleash the weight-lowering properties of leptin has injected new hope into the field. Fascinatingly, these leptin-sensitising agents seem to act via distinct metabolic...

  11. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents.

    Directory of Open Access Journals (Sweden)

    Mario Perello

    Full Text Available The adipocyte-derived hormone leptin acts in the brain to reduce body weight and fat mass. Recent studies suggest that parvocellular oxytocin (OXT neurons of the hypothalamic paraventricular nucleus (PVN can mediate body weight reduction through inhibition of food intake and increased energy expenditure. However, the role of OXT neurons of the PVN as a primary target of leptin has not been investigated. Here, we studied the potential role of OXT neurons of the PVN in leptin-mediated effects on body weight regulation in fasted rats. We demonstrated that intracerebroventricular (ICV leptin activates STAT3 phosphorylation in OXT neurons of the PVN, showed that this occurs in a subpopulation of OXT neurons that innervate the nucleus of the solitary tract (NTS, and provided further evidence suggesting a role of OXT to mediate leptin's actions on body weight. In addition, our results indicated that OXT neurons are responsive to ICV leptin and mediate leptin effects on body weight in diet induced obese (DIO rats, which are resistant to the anorectic effects of the hormone. Thus, we conclude that leptin targets a specific subpopulation of parvocellular OXT neurons of the PVN, and that this action may be important for leptin's ability to reduce body weight in both control and obese rats.

  12. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Science.gov (United States)

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice.

    Science.gov (United States)

    Hakim, Fahed; Wang, Yang; Carreras, Alba; Hirotsu, Camila; Zhang, Jing; Peris, Eduard; Gozal, David

    2015-01-01

    Sleep fragmentation (SF) is highly prevalent and may constitute an important contributing factor to excessive weight gain and the metabolic syndrome. Increased endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) leading to the attenuation of leptin receptor signaling in the hypothalamus leads to obesity and metabolic dysfunction. Mice were exposed to SF and sleep control (SC) for varying periods of time during which ingestive behaviors were monitored. UPR pathways and leptin receptor signaling were assessed in hypothalami. To further examine the mechanistic role of ER stress, changes in leptin receptor (ObR) signaling were also examined in wild-type mice treated with the ER chaperone tauroursodeoxycholic acid (TUDCA), as well as in CHOP-/+ transgenic mice. Fragmented sleep in male mice induced increased food intake starting day 3 and thereafter, which was preceded by increases in ER stress and activation of all three UPR pathways in the hypothalamus. Although ObR expression was unchanged, signal transducer and activator of transcription 3 (STAT3) phosphorylation was decreased, suggesting reduced ObR signaling. Unchanged suppressor of cytokine signaling-3 (SOCS3) expression and increases in protein-tyrosine phosphatase 1B (PTP1B) expression and activity emerged with SF, along with reduced p-STAT3 responses to exogenous leptin. SF-induced effects were reversed following TUDCA treatment and were absent in CHOP -/+ mice. SF induces hyperphagic behaviors and reduced leptin signaling in hypothalamus that are mediated by activation of ER stress, and ultimately lead to increased PTP1B activity. ER stress pathways are therefore potentially implicated in SF-induced weight gain and metabolic dysfunction, and may represent a viable therapeutic target. © 2014 Associated Professional Sleep Societies, LLC.

  14. Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth.

    Science.gov (United States)

    McMillen, I C; Muhlhausler, B S; Duffield, J A; Yuen, B S J

    2004-08-01

    Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the 'unilocular' component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a 'lipostatic' role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.

  15. Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

    Science.gov (United States)

    Biesdorf, C; Wang, A-L; Topic, B; Petri, D; Milani, H; Huston, J P; de Souza Silva, M A

    2015-09-01

    Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. (a) These results confirm the importance of DA release in the NAc for

  16. [Leptin--an interim evaluation].

    Science.gov (United States)

    Bodner, J; Ebenbichler, C F; Lechleitner, M; Ritsch, A; Sandhofer, A; Gander, R; Wolf, H J; Huter, O; Patsch, J R

    1998-03-27

    The discovery of leptin, the product of the obese (ob)-gene, has broadened the horizons of research on energy balance. This hormone, produced and secreted by adipose tissue and some placental cells, finds its way to the hypothalamus, where it binds to the leptin receptors and signals satiety through the neuroendocrine axis. The fact that adipose tissue is not merely a storage depot, but also an important endocrine tissue, has revived the interest in the "lipostatic" theory of body fat regulation and has initiated many research efforts in the field of obesity, anorexia nervosa, bulimia, reproduction and haematology.

  17. Influence of dexamethasone and weight loss on the regulation of serum leptin levels in obese individuals

    Directory of Open Access Journals (Sweden)

    D.D.G. Lerario

    2001-04-01

    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.

  18. 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)

  19. Specific Features of the Hypothalamic Leptin Signaling Response to Cold Exposure Are Reflected in Peripheral Blood Mononuclear Cells in Rats and Ferrets

    Directory of Open Access Journals (Sweden)

    Bàrbara Reynés

    2017-08-01

    Full Text Available Objectives: Cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. The aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia.Methods: We analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months, as well as in ferrets. We also evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses.Results: As expected, cold exposure induced hypoleptinemia in rats, which could be responsible for the increased ratio of orexigenic/anorexigenic peptides gene expression in the hypothalamus, mainly due to decreased anorexigenic gene expression, especially in young animals. In ferrets, which resemble humans more closely, cold exposure induced greater changes in hypothalamic mRNA levels of orexigenic genes. Despite the key role of leptin in food intake control, the effect of cold exposure on the expression of key hypothalamic leptin signaling cascade genes is not clear. In our study, cold exposure seemed to affect leptin signaling in 4-month-old rats (increased Socs3 and Lepr expression, likely associated with the smaller-increase in food intake and decreased body weight observed at this particular age. Similarly, cold exposed ferrets showed greater hypothalamic Socs3 and Stat3 gene expression. Interestingly, peripheral blood mononuclear cells (PBMC mimicked the hypothalamic increase in Lepr and Socs3 observed in 4-month-old rats, and the increased Socs3 mRNA expression observed in ferrets in response to cold exposure.Conclusions: The most outstanding result of our study is that PBMC reflected the specific modulation of leptin signaling observed in both animal models, rats and ferrets, which points forwards PBMC as easily obtainable biological material to be

  20. 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.

  1. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein.

    Science.gov (United States)

    Shimada, Yasuko; Komatsu, Yasutaka; Ikezawa-Suzuki, Ikuyo; Tai, Hideaki; Sugita, Noriko; Yoshie, Hiromasa

    2010-08-01

    Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047). Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

  2. Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

    Directory of Open Access Journals (Sweden)

    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. 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...

  4. 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.

  5. Effect of leptin on proliferation and apoptosis of cholangiocarcinoma QBC939 cells

    Directory of Open Access Journals (Sweden)

    DAI Kai

    2013-03-01

    Full Text Available ObjectiveTo determine whether leptin can exert anti-proliferative and pro-apoptotic effects on human cholangiocarcinoma cells and to investigate the underlying molecular mechanisms. MethodsHuman cholangiocarcinoma QBC939 cells were cultured and treated with different concentrations of leptin. Changes in the proliferation rate were measured by the MTT assay. Changes in cell cycle and in the apoptosis incidence rate were detected by flow cytometry. Changes in cyclin D1, bax and bcl-2 gene expression were detected by measuring mRNA levels by real-time quantitative reverse transcription-polymerase chain reaction (qPCR. Changes in caspase-3 protease activity were detected by fluorometric assay. ResultsLeptin treatment significantly increased the proliferation rate of QBC939 cells in a dose- and time-dependent manner. Compared to untreated QBC939 cells, leptin treatment led to significantly more G0/G1 to S phase transition and significantly lower apoptosis rate. In addition, leptin-treated QBC939 cells showed enhanced mRNA expression of cyclin D1 and bcl-2, but decreased mRNA expression of bax. The leptin treatment also led to decreased caspase-3 activity. ConclusionLeptin promotes S to G0/G1 phase transition and proliferation, but inhibits apoptosis, of human cholangiocarcinoma cells in vitro.

  6. Leptin promotes wound healing in the skin.

    Directory of Open Access Journals (Sweden)

    Susumu Tadokoro

    Full Text Available Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

  7. Congenital leptin deficiency and thyroid function

    Directory of Open Access Journals (Sweden)

    Paz-Filho Gilberto

    2009-11-01

    Full Text Available Abstract Thyroid function is closely related to leptin's secretion by the adipose tissue. In states of leptin-deficiency, the circadian rhythm of TSH is altered, leading to central hypothyroidism in animal models. In humans, central hypothyroidism has also been described in rare cases of congenital leptin deficiency. However, the thyroid phenotype in these cases is heterogeneous, with the occurrence of central hypothyroidism in a minority of cases. Here we describe thyroid function in four leptin-deficient humans (2 males aged 5 and 27, and 2 females aged 35 and 40, before and during leptin replacement with recombinant human methionyl leptin (r-metHuLeptin. The child was evaluated for four years, and the adults, for eight years. In addition, the adults were submitted to a brief withdrawal of leptin during six weeks in the sixth year. Our results show that, regardless of leptin replacement, our leptin-deficient patients have normal thyroid function. In spite of having an important role in regulating the hypothalamic-pituitary-thyroidal axis, leptin is not required for normal thyroid function. Trial Registration ClinicalTrials.gov Identifiers: NCT00659828 and NCT00657605

  8. Leptin Receptor Deficiency is Associated With Upregulation of Cannabinoid 1 Receptors in Limbic Brain Regions

    Science.gov (United States)

    THANOS, PANAYOTIS K.; RAMALHETE, ROBERTO C.; MICHAELIDES, MICHAEL; PIYIS, YIANNI K.; WANG, GENE-JACK; VOLKOW, NORA D.

    2009-01-01

    Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid 1 receptors (CB1R) in overeating and the effects of food deprivation on CB1R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB1R (CB1R binding levels) were assessed using [3H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB1R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB1R binding levels than Le in most brain regions and food restriction was associated with higher CB1R levels in all brain regions in Ob, but not in Le rats. CB1R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB1R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB1R and that leptin interferes with CB1R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin. PMID:18563836

  9. Predictors of Cord Blood Leptin Level in Pregnancies Complicated With Preeclampsia, Fetal Growth Restriction and in Normal Pregnancies

    Directory of Open Access Journals (Sweden)

    Nilgün Öztürk Doğan

    2007-04-01

    CONCLUSION: Regulation of cord blood leptin level is a complex process involving fetal gender and fetal anthropometric variables as well as cord blood cortisol, intrauterine growth and hypoxia. Leptin level is decreased in cases of placental insufficiency like IUGR but not in uncomplicated preeclampsia alone.

  10. Review of theories on development of ovarian cancer. Leptin as a potential agent engaged in carcinogenesis

    International Nuclear Information System (INIS)

    Markowska, A.

    2007-01-01

    Many different hypotheses and theories have been formulated regarding the development of sporadic ovarian cancer. The augmented risk is associated with nulliparity or low fecundity. Apart from changes in the genital system, leptin can be linked in several ways to infertility or low fecundity, from poor alimentation (severe dieting) and its effects on the hypothalamushypophysis-ovary axis to improper blastocyst implantation in the endometrium. Ovulation used to be regarded as representing one of the factors which promote the development of ovarian cancer due to the associated lesions of the ovarian epithelium and the development of inclusion cysts. The risk is reduced by the long-term use of contraceptive pills. However, it has been demonstrated, that hormonal contraception is linked to the stabilization of plasma leptin levels and that it, possibly, has less pronounced effects on target tissues. In view of the suggestions on leptin involvement, the hypothesis regarding the effects of HRT on ovarian cancer development remains unsupported since leptin levels during a course of HRT manifest no increases or decreases- they remain stable. The inflammatory theory of ovarian cancer development might also be linked to the potential involvement of leptin in the pathogenesis of endometriosis, promoting endometrioid and clarocellular ovarian cancers. Leptin has been shown to be linked to the development of endometriosis, particularly due to its mitogenic and angiogenic effects. Bilateral ovariectomy, aimed at preventing the development of ovarian cancer, induces a decrease in serum leptin levels, in contrast to the reversible effects of pharmacological gonadectomy. Ovarian cancer develops more frequently in women who have high living standards, which is significantly associated with increased BMI and augmented serum leptin levels. The described theory concerning the two pathways of ovarian cancer development, including one typical for more aggressive serous cancers, may

  11. 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

  12. 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

  13. 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.

  14. Leptin expression in ruminants: nutritional and physiological regulations in relation with energy metabolism.

    Science.gov (United States)

    Chilliard, Y; Delavaud, C; Bonnet, M

    2005-07-01

    Leptin, mainly produced in adipose tissue (AT), is a protein involved in the central and/or peripheral regulation of body homeostasis, energy intake, storage and expenditure, fertility and immune functions. Its role is well documented in rodent and human species, but less in ruminants. This review is focused on some intrinsic and extrinsic factors which regulate adipose tissue leptin gene expression and leptinemia in cattle, sheep, goat and camel: age, physiological status (particularly pregnancy and lactation) in interaction with long-term (adiposity) and short-term effects of feeding level, energy intake and balance, diet composition, specific nutrients and hormones (insulin, glucose and fatty acids), and seasonal non-dietary factors such as photoperiod. Body fatness strongly regulates leptin and its responses to other factors. For example, leptinemia is higher after underfeeding or during lactation in fat than in lean animals. Physiological status per se also modulates leptin expression, with lactation down-regulating leptinemia, even when energy balance (EB) is positive. These results suggest that leptin could be a link between nutritional history and physiological regulations, which integrates the animal's requirements (e.g., for a pregnancy-lactation cycle), predictable food availability (e.g., due to seasonal variations) and potential for survival (e.g., body fatness level). Reaching permissive leptin thresholds should be necessary for pubertal or postpartum reproductive activity. In addition to the understanding of leptin yield regulation, these data are helpful to understand the physiological significance of changes in leptin secretion and leptin effects, and how husbandry strategies could integrate the adaptative capacities of ruminant species to their environment.

  15. Inhibitory effect of leptin on rosiglitazone-induced differentiation of primary adipocytes prepared from TallyHO/Jng mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ki Young; Kim, Joo Young; Sung, Yoon-Young; Jung, Won Hoon; Kim, Hee-Youn; Park, Ji Seon; Cheon, Hyae Gyeong [Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yuseong, 305-600 Daejon (Korea, Republic of); Rhee, Sang Dal, E-mail: sdrhee@krict.re.kr [Medicinal Science Division, Korea Research Institute of Chemical Technology, 100 Jang-dong, Yuseong, 305-600 Daejon (Korea, Republic of)

    2011-03-25

    Research highlights: {yields} In this study, we investigated the effects of leptin on adipocyte differentiation prepared from subcutaneous fat of TallyHo mice. {yields} Leptin inhibited the adipocytes differentiation at physiological concentration via inhibition of PPAR{gamma} expression. {yields} Inhibitors of ERK and STAT1 restored the leptin's inhibitory activity both in vitro and in vivo. -- Abstract: The effects of leptin on rosiglitazone-induced adipocyte differentiation were investigated in the primary adipocytes prepared from subcutaneous fat of TallyHO/Jng (TallyHO) mouse, a recently developed model animal for type 2 diabetes mellitus (T2DM). The treatment of leptin inhibited the rosiglitazone-induced adipocyte differentiation with a decreased expression of peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) a key adipogenic transcription factor, both in mRNA and protein levels. Leptin (10 nM) was sufficient to inhibit the adipocyte differentiation, which seemed to come from increased expression of leptin receptor genes in the fat of TallyHO mice. The inhibition of adipogenesis by leptin was restored by the treatment of inhibitors for extracellular-signal-regulated kinase (ERK) (PD98059) and signal transducer and activator of transcription-1 (STAT1) (fludarabine). Furthermore, in vivo intraperitoneal administration of PD98059 and fludarabine increased the PPAR{gamma} expression in the subcutaneous fat of TallyHO mice. These data suggest that leptin could inhibit the PPAR{gamma} expression and adipocyte differentiation in its physiological concentration in TallyHO mice.

  16. Bis(tributyltin)oxide (TBTO) decreases the food allergic response against peanut and ovalbumin in Brown Norway rats

    NARCIS (Netherlands)

    Jonge, J.D. de; Ezendam, J.; Knippels, L.M.J.; Odink, J.; Pourier, M.S.; Penninks, A.H.; Pieters, R.; Loveren, H. van

    2007-01-01

    Other factors than the allergen itself may be of importance in the development of food allergy. This report describes the influence of the immunosuppressive compound bis(tributyltin)oxide (TBTO), present in the food chain, on the development of food allergy to peanut or ovalbumin in Brown Norway

  17. Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.

    Science.gov (United States)

    Lambert, P D; Anderson, K D; Sleeman, M W; Wong, V; Tan, J; Hijarunguru, A; Corcoran, T L; Murray, J D; Thabet, K E; Yancopoulos, G D; Wiegand, S J

    2001-04-10

    Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

  18. Lung function testing according leptin levels in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    O. Radchenko

    2017-02-01

    Full Text Available Chronic obstructive pulmonary disease (COPD belongs to urgent medical and social problems of our time. Prognosis of COPD is often determined by a comorbidity, in particular obesity. The key chain, which unites COPD and obesity, is systemic inflammation, in the development of which the hormone of fatty tissue leptin plays an important role. The presence of receptors to leptin in the alveolar and bronchial epithelial cells, in smooth muscle tissue and submucous bronchial membrane allowes to assume that leptin takes pathogenetic part in COPD progression. The aim of our research was to estimate the leptin level in COPD patient and analyze changes of the respiratory function depending on it. Methods. We have been examined 26 patients with exacerbation of COPD (13 male and 13 female, 58 y.o. and 20 healthy people representative by gender, age and body mass. The level of serum leptin has been defined by the solid phase enzyme linked immunosorbent analysis, lung function – by computed testing. Results and conclusion. With the leptin level increase all of the lung function parameters progressively decreased, most significant - forced vital capacity and peak expiratory flow. Patients with hyperleptinemia had significantly lower measurements of forced expiratory volume in 1 second and vital lungs capacity. Severe degree of both obstructive and restrictive changes has been found more often among patients with hyperleptinemia and leptin level has been associated with the bronchial obstruction severity.

  19. 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.

  20. Impact of leptin on memory function and hippocampal structure in mild cognitive impairment.

    Science.gov (United States)

    Witte, A Veronica; Köbe, Theresa; Graunke, Anders; Schuchardt, Jan Philipp; Hahn, Andreas; Tesky, Valentina A; Pantel, Johannes; Flöel, Agnes

    2016-12-01

    Metabolic changes have been suggested to contribute to dementia and its precursor mild cognitive impairment (MCI), yet previous results particularly for the "satiety hormone" leptin are mixed. Therefore, we aimed to determine if MCI patients show systematic differences in leptin, independent of sex, adipose mass, age, and glucose and lipid metabolism, and whether leptin levels correlated with memory performance and hippocampal integrity. Forty MCI patients (20 females, aged 67 years ± 7 SD) were compared to 40 healthy controls (HC) that were pair-wise matched for sex, age, and body fat. Memory performance was assessed using the auditory verbal learning test. Volume and microstructure of the hippocampus were determined using 3T-neuroimaging. Fasting serum markers of leptin, glucose and lipid metabolism, and other confounding factors were assayed. MCI patients, compared with HC, showed lower serum leptin, independent of sex, age, and body fat (P memory and lower volume and microstructural integrity within hippocampal subfields. While leptin and memory were not significantly correlated, mediation analyses indicated that lower leptin contributed to poorer memory through its negative effect on right hippocampus volume and left hippocampus microstructure. We demonstrated that MCI is associated with lower serum leptin independent of sex, age, body fat, glucose, and lipid metabolism. Our data further suggest that inefficient leptin signaling could partly contribute to decreases in memory performance through changes in hippocampus structure, a hypothesis that should now be verified in longitudinal studies. Hum Brain Mapp 37:4539-4549, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function.

    Science.gov (United States)

    Zuure, Wieteke A; Roberts, Amy L; Quennell, Janette H; Anderson, Greg M

    2013-11-06

    The adipocyte-derived hormone leptin acts in the brain to modulate the central driver of fertility: the gonadotropin releasing hormone (GnRH) neuronal system. This effect is indirect, as GnRH neurons do not express leptin receptors (LEPRs). Here we test whether GABAergic or glutamatergic neurons provide the intermediate pathway between the site of leptin action and the GnRH neurons. Leptin receptors were deleted from GABA and glutamate neurons using Cre-Lox transgenics, and the downstream effects on puberty onset and reproduction were examined. Both mouse lines displayed the expected increase in body weight and region-specific loss of leptin signaling in the hypothalamus. The GABA neuron-specific LEPR knock-out females and males showed significantly delayed puberty onset. Adult fertility observations revealed that these knock-out animals have decreased fecundity. In contrast, glutamate neuron-specific LEPR knock-out mice displayed normal fertility. Assessment of the estrogenic hypothalamic-pituitary-gonadal axis regulation in females showed that leptin action on GABA neurons is not necessary for estradiol-mediated suppression of tonic luteinizing hormone secretion (an indirect measure of GnRH neuron activity) but is required for regulation of a full preovulatory-like luteinizing hormone surge. In conclusion, leptin signaling in GABAergic (but not glutamatergic neurons) plays a critical role in the timing of puberty onset and is involved in fertility regulation throughout adulthood in both sexes. These results form an important step in explaining the role of central leptin signaling in the reproductive system. Limiting the leptin-to-GnRH mediators to GABAergic cells will enable future research to focus on a few specific types of neurons.

  2. Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

    Science.gov (United States)

    Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2018-01-01

    Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

    African Journals Online (AJOL)

    use

    2011-12-05

    Dec 5, 2011 ... Lord et al., 1998) have shed light on the influence of leptin on both the .... A weak correlation between leptin serum levels and cow body condition ... Detection of polymorphisms in the ovine leptin (LEP) gene: .... Signals that.

  4. Genetic Variation in the Leptin Receptor Gene, Leptin, and Weight Gain in Young Dutch Adults

    NARCIS (Netherlands)

    Rossum, van C.T.M.; Hoebee, B.; Baak, van M.A.; Mars, M.; Saris, W.H.M.; Seidell, J.C.

    2003-01-01

    Objective: To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. Research Methods and Procedures: From two large prospective cohorts in The Netherlands (n = 17, 500), we compared the baseline leptin of 259 subjects who had gained an

  5. Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene

    NARCIS (Netherlands)

    Mars, M.; Rossum, van C.T.M.; Graaf, de C.; Hoebee, B.; Groot, de C.P.G.M.; Kok, F.J.

    2004-01-01

    Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in

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

    Science.gov (United States)

    Savino, Francesco; Sardo, Allegra; Rossi, Lorenza; Benetti, Stefania; Savino, Andrea; Silvestro, Leandra

    2016-06-21

    This study investigates correlations between mother and infant Body Mass Index (BMI), their serum leptin values and breast milk leptin concentration in early infancy. 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. 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). 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.

  7. Role of proopiomelanocortin neuron Stat3 in regulating arterial pressure and mediating the chronic effects of leptin.

    Science.gov (United States)

    Dubinion, John H; do Carmo, Jussara M; Adi, Ahmad; Hamza, Shereen; da Silva, Alexandre A; Hall, John E

    2013-05-01

    Although signal transducer and activator of transcription 3 (Stat3) is a key second messenger by which leptin regulates appetite and body weight, its role in specific neuronal populations in metabolic regulation and in mediating the chronic effects of leptin on blood pressure is unknown. The current study tested the hypothesis that Stat3 signaling in proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on mean arterial pressure (MAP), as well as on glucose regulation, energy expenditure, and food intake. Stat3(flox/flox) mice were crossed with POMC-Cre mice to generate mice with Stat3 deletion specifically in POMC neurons (Stat3(flox/flox)/POMC-Cre). Oxygen consumption (Vo2), carbon dioxide respiration (Vco2), motor activity, heat production, food intake, and MAP were measured 24 hours/d. After baseline measurements, leptin was infused (4 μg/kg per min, IP) for 7 days. Stat3(flox/flox)/POMC-Cre mice were hyperphagic, heavier, and had increased respiratory quotients compared with control Stat3(flox/flox) mice. Baseline MAP was not different between the groups, and chronic leptin infusion reduced food intake similarly in both groups (27 versus 29%). Vo2, Vco2, and heat production responses to leptin were not significantly different in control and Stat3(flox/flox)/POMC-Cre mice. However, leptin-mediated increases in MAP were completely abolished, and blood pressure responses to acute air-jet stress were attenuated in male Stat3(flox/flox)/POMC-Cre mice. These results indicate that Stat3 signaling in POMC neurons is essential for leptin-mediated increases in MAP, but not for anorexic or thermogenic effects of leptin.

  8. Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.

    Science.gov (United States)

    Llidó, Anna; Bartolomé, Iris; Darbra, Sònia; Pallarès, Marc

    2016-08-01

    Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Role of leptin in delayed embryonic development in the Indian short-nosed fruit bat, Cynopterus sphinx.

    Science.gov (United States)

    Banerjee, A; Meenakumari, K J; Krishna, A

    2010-08-01

    An adiposity-associated rise in leptin occurs at the time of delayed embryonic development in Cynopterus sphinx. The aim of present study was to examine the mechanism by which leptin may inhibit progesterone, and therefore could be responsible for delayed development. The study showed a significant increase in circulating leptin level during the period of increased fat accumulation, which coincided with significant decrease in serum progesterone level and delayed embryonic development in C. sphinx. The study showed increased Ob-R expression in the corpus luteum and in the utero-embryonic unit during the period of delayed embryonic development. The in vitro study showed suppressive effect of leptin on progesterone synthesis. The effect of high dose of leptin on ovarian steroidogenesis was found to be mediated through decreased expression of StAR and LH-R proteins in the ovary. The treatment with leptin caused increased expression of STAT 3 and iNOS proteins in the ovary, which correlated with decreased expression of StAR protein in the ovary. The inhibitory effects of leptin on progesterone synthesis in the ovary are thus mediated through STAT 3 and iNOS-NO signaling pathways. This study further demonstrated low expression of PCNA coinciding with the increased concentration of the leptin receptor in the utero-embryonic unit and high circulating leptin level during November. In conclusion, adiposity associated increased leptin level during November-December might play role in suppressing progesterone synthesis in the corpus luteum as well as suppressing the rate of cell-proliferation in the utero-embryonic unit thereby causing delayed embryonic development in C. sphinx. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Effect of different stress factors on IL-6 and leptin expression in HELA cell cultures

    International Nuclear Information System (INIS)

    Chu Zhenwei; Yang Tao; Wang Luhuan; Hao Xiuhua; Yan Guangtao

    2009-01-01

    Objective: To study the effect of three stress factors high glucose (HG), lipopolysaccharide (LPS) and hydrogen peroxide (H 2 O 2 ) on the expression of culture supernatant IL-6 (IL-6) and leptin contents of HELA cell line. Methods: HELA cell culture models of severe inflammatory response syndrome were prepared with cultures treated with 50 mmol/L glucose (HG), 4 μg/ ml LPS and 100 μmol/L H 2 O 2 respectively and supernatant contents of IL-6 and leptin were measured with RIA at 1h, 6h and 24h. Results: Generally speaking, the culture supernatant contents of IL-6 gradually increased and leptin contents gradually decreased with significant differences from those in cultures not treated with either stress factor at 6h and 12h (P<0.05). Conclusion: Leptin as a possible anti-inflammatory cytokine might plays an important protective role in severe inflammatory response. (authors)

  11. Serum Leptin Levels in Post-Hepatitis Band C Liver Cirrhosis

    International Nuclear Information System (INIS)

    Nosseir, N.M.; Abdel-Messeih, Ph.L.; Ismael, N.E.R.

    2010-01-01

    A healthy liver is able to regenerate most of its own cells when they become damaged, with the end stage cirrhosis the liver no longer replace damaged cells. Leptin is a hormone that plays a key role in regulating energy intake and expenditure including appetite and metabolism. This study was done to investigate serum Leptin level in liver cirrhosis (post hepatitis B and post-hepatitis C cirrhosis), as well as to determine its level in relation to liver functions in cirrhotic patients. In this study, serum Leptin level was significantly lower in post-hepatitis B cirrhosis than controls and insignificant changes were observed in patients with post-hepatitis C cirrhosis. Also a significant reduction in leptin level was observed as liver functions worsen as indicated by albumin decrease.

  12. The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

    Science.gov (United States)

    Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

    2015-01-01

    We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

  13. Serum Leptin levels do not correlate with disease activity in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Sibel Yilmaz Oner

    2015-01-01

    Full Text Available Objectives Leptin, is a fat tissue hormone which effects energy expenditure , food intake , hematopoiesis, osteogenesis, angiogenesis, reproductive and immune systems. We aimed to determine serum leptin levels and investigate the association between disease activity and other parameters in RA patients. Methods Patients with RA (n=106 as the study group, healthy controls (n=52 and osteoarthritis (OA patients (n=37 as a control group were enrolled to the study. RA patients were categorized in four different groups according to DAS28 scores: remission ,low (LDA, moderate (MDA or high (HDA disease activity . Results No differences were present between the body mass indices of the three groups. Mean leptin levels in RA patients, OA group and healthy individuals were 25,60±13,41, 23,03±11,51 and 23,81±12,85 ng/ml, respectively and no significant difference was present between the groups. Nine of (8,5% RA patients were in remission, 16 (15,1% were in LDA, 40 (37,7% in MDA and 41 (38,7% were in HDA. Leptin levels did not correlate with DAS28 scores of RA patients (r=-0,12, p=0,11. Mean leptin levels in RA patients with remission was 32,65±7, 28 in LDA 23,94±10,94 in MDA 26,73±14,92 and in HDA 23,59±13,50 ng/ml (p=NS. No associations were observed between leptin levels and CRP, ESR, RF positivity and disease duration. Conclusions Our study revealed no correlation of disease activity and serum leptin levels. Therefore leptin does not seem to be an appropriate biomarker to monitorize inflammation in RA.

  14. Study on changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis

    International Nuclear Information System (INIS)

    Sun Zihan; Luo Nanping; Niu Aijun; Qi Falian

    2006-01-01

    Objective: To investigate the changes of serum leptin, IGF-I and IL-2 levels in elderly subjects with osteoporosis. Methods: Serum leptin, IGF-I, IL-2 levels (with RIA), total cholesterol contents (with biochemical method) and bone mineral density (BMD) were examined in 65 aged patients with osteoporosis. Results: The serum leptin levels in subjects with osteoporosis were significantly higher than controls (P<0.01). The serum IGF-I and IL-2 levels in subjects with osteoporosis were significantly lower than those in controls (P<0.05, P<0.01). The BMD was positively correlated with the IGF-I levels and negatively correlated with leptin level. Conclusion: Derangement of leptin and IGF-I, IL-2 metabolism is one of the major causes of decreased bone mass and bone formation elderly subjects with osteoporosis. Measurement of serum levels of these parameters is of diagnostic help. (authors)

  15. Inhibiting Endogenous Cortisol Blunts the Meal-Entrained Rise in Serum Leptin

    Science.gov (United States)

    Laferrère, Blandine; Abraham, Cynthia; Awad, Marianne; Jean-Baptiste, Stephanie; Hart, Allison B.; Garcia-Lorda, Pilar; Kokkoris, Peter; Russell, Colleen D.

    2010-01-01

    Context Administration of glucocorticoids increases serum leptin levels in lean and obese individuals. A morning meal produces an increase in insulin, a cortisol peak, and an increase in leptin; these changes do not occur during fasting. Objective The objective of this study was to investigate whether inhibiting endogenous cortisol secretion with metyrapone decreases 24-h serum leptin levels and to determine whether a meal-related midmorning surge in cortisol is a prerequisite for the meal-entrained nocturnal rise in leptin. Design This was a randomized, cross-over study. Setting The study was performed at the General Clinical Research Center. Participants Lean males were studied. Intervention In study 1, seven lean men were studied for 24 h while their endogenous cortisol secretions were manipulated as follows: 1) CONTROL; 2) cortisol suppression by metyrapone (MET); and 3) MET and oral hydrocortisone (at 0900 h) (MET + CORT). Subjects were all fed a eucaloric diet (two meals at 1100 and 1700 h). In study 2, six men were studied without pharmacological intervention for 24 h on two occasions: once under a complete fast (FAST) and once in a feeding condition (one meal at 1100 h; FED). Main Outcome Measure The main outcome measure was serum leptin. Results MET significantly suppressed serum cortisol at 0800 h, midmorning, and over the 24-h period. As a result of cortisol suppression, 24-h serum leptin levels were decreased vs. control values despite similar insulin responses to meals. Administering a single dose of hydrocortisone to MET subjects potently stimulated serum leptin compared with the effect of MET alone. Conclusions Our data demonstrate that endogenous cortisol secretion is necessary for the maintenance of serum leptin levels over 24 h in lean, normally fed males. PMID:16537679

  16. Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults.

    Science.gov (United States)

    van Rossum, Caroline T M; Hoebee, Barbara; van Baak, Marleen A; Mars, Monica; Saris, Wim H M; Seidell, Jacob C

    2003-03-01

    To investigate the association between leptin levels, polymorphisms in the leptin receptor (LEPR) gene, and weight gain. From two large prospective cohorts in The Netherlands (n = 17,500), we compared the baseline leptin of 259 subjects who had gained an average of 12.6 kg (range 5.5 to 33 kg) with 277 subjects who kept stable weight (range -2.6 to 3.1 kg) after a mean follow-up of 6.8 years. Three polymorphisms in the LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) were determined. Weight gainers had significantly higher baseline leptin levels than those who kept stable weight (odds ratio = 1.27, 95% confidence interval 1.1 to 1.5, per SD increase in log(e)-transformed leptin). Weight gainers with the Arg109 or the Arg223 alleles had higher leptin levels compared with the noncarriers of these alleles. Only among men, the association between leptin and weight gain tended to be stronger among those with an Arg223 allele compared with those without this mutation. Relatively high leptin levels predict weight gain, suggesting that leptin resistance plays a role in the development of obesity in the general population. Higher leptin levels for those with a Lys109Arg or Gln223Arg mutation (or a linked other marker) may imply that these subjects have a modified functional leptin receptor. However, the role of these mutations on weight gain is limited.

  17. Leptin, immune responses and autoimmune disease. Perspectives on the use of leptin antagonists.

    Science.gov (United States)

    Peelman, F; Iserentant, H; Eyckerman, S; Zabeau, L; Tavernier, J

    2005-01-01

    The pivotal role of leptin in regulating body weight and energy homeostasis is very well established. More recently, leptin also emerged as an important regulator of T-cell-dependent immunity. Reduced leptin levels, as observed during periods of starvation, correlate with an impaired cellular immune response, whereby especially the T(H)1 pro-inflammatory immune response appears to be affected. Physiologically, this could reflect the high energy demand of such processes, which are suppressed in animals or people with nutrient shortage. Several autoimmune diseases are T(H)1 T-cell dependent. In line with a pro-inflammatory role for leptin, animal models of leptin deficiency are markedly resistant to a variety of T-cell dependent autoimmune diseases. Here, we review the role of leptin in immune responses, with emphasis on autoimmune diseases. The design and potential use of leptin antagonists is also discussed.

  18. 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

    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 leptin...... 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...... 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...

  19. Presynaptic Regulation of Leptin in a Defined Lateral Hypothalamus-Ventral Tegmental Area Neurocircuitry Depends on Energy State.

    Science.gov (United States)

    Liu, Jing-Jing; Bello, Nicholas T; Pang, Zhiping P

    2017-12-06

    Synaptic transmission controls brain activity and behaviors, including food intake. Leptin, an adipocyte-derived hormone, acts on neurons located in the lateral hypothalamic area (LHA) to maintain energy homeostasis and regulate food intake behavior. The specific synaptic mechanisms, cell types, and neural projections mediating this effect remain unclear. In male mice, using pathway-specific retrograde tracing, whole-cell patch-clamp recordings and post hoc cell type identification, we found that leptin reduces excitatory synaptic strength onto both melanin-concentrating hormone- and orexin-expressing neurons projecting from the LHA to the ventral tegmental area (VTA), which may affect dopamine signaling and motivation for feeding. A presynaptic mechanism mediated by distinct intracellular signaling mechanisms may account for this regulation by leptin. The regulatory effects of leptin depend on intact leptin receptor signaling. Interestingly, the synaptic regulatory function of leptin in the LHA-to-VTA neuronal pathway is highly sensitive to energy states: both energy deficiency (acute fasting) and excessive energy storage (high-fat diet-induced obesity) blunt the effect of leptin. These data revealed that leptin may regulate synaptic transmission in the LHA-to-VTA neurocircuitry in an inverted "U-shape" fashion dependent on plasma glucose levels and related to metabolic states. SIGNIFICANCE STATEMENT The lateral hypothalamic area (LHA) to ventral tegmental area (VTA) projection is an important neural pathway involved in balancing whole-body energy states and reward. We found that the excitatory synaptic inputs to both orexin- and melanin-concentrating hormone expressing LHA neurons projecting to the VTA were suppressed by leptin, a peptide hormone derived from adipocytes that signals peripheral energy status to the brain. Interestingly, energy states seem to affect how leptin regulates synaptic transmission since both the depletion of energy induced by acute food

  20. The interactive effects of a gradual temperature decrease and long-term food deprivation on cardiac and hepatic blood flows in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Petersen, L H; Dzialowski, E; Huggett, D B

    2011-11-01

    The aim of the present study was to determine the extent to which the fish liver is perfused with blood. Transonic® flow probes were therefore implanted around the ventral aorta and hepatic vein(s) to record baseline blood flows in rainbow trout (Oncorhynchus mykiss) previously held under two different feeding regimes (food-deprived or fed to satiation, 8-12 weeks). Fish from both groups were exposed to a gradual temperature decrease (12°C to 5°C) and physical disturbance. Cardiac output (Q), stroke volume (Sv) and hepatic venous blood flow (HVBF) were significantly reduced in food-deprived trout at 12°C. Heart rate was not significantly affected by nutritional status, but was significantly reduced when temperature was decreased to 5°C. Physically disturbing each fish at 12°C and 5°C showed that the performance capacity of the heart was not affected by food deprivation as the capacity to increase Q and Sv was not reduced in the food-deprived group. Overall this study showed that food deprivation in rainbow trout reduced cardiac and hepatic blood flows. However, long-term food deprivation did not affect the capacity of the heart to acutely increase performance. Copyright © 2011. Published by Elsevier Inc.

  1. 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 ...

  2. Cord Blood Leptin Levels in Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Özlem Şengül

    2010-08-01

    CONCLUSION: In this study there is a minimal clinical effect of cord blood leptin on macrosomia in women with GD, although it is increased in GD and associated with birthweight. Therefore overgrowth may be a result of direct anabolic effect of insulin, rather than indirect effect via leptin.

  3. 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 ...

  4. Nutritional status modulates plasma leptin, AMPK and TOR activation, and mitochondrial biogenesis: Implications for cell metabolism and growth in skeletal muscle of the fine flounder.

    Science.gov (United States)

    Fuentes, Eduardo N; Safian, Diego; Einarsdottir, Ingibjörg Eir; Valdés, Juan Antonio; Elorza, Alvaro A; Molina, Alfredo; Björnsson, Björn Thrandur

    2013-06-01

    Insight of how growth and metabolism in skeletal muscle are related is still lacking in early vertebrates. In this context, molecules involved in these processes, such as leptin, AMP-activated protein kinase (AMPK), target of rapamicyn (TOR), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, and oxidative phosphorylation complexes (OXPHOS), were assessed in the skeletal muscle of a fish species. Periods of fasting followed by a period of refeeding were implemented, using the fine flounder as a model (Paralichthys adspersus). This species exhibits remarkably slow growth and food intake, which is linked to an inherent growth hormone (GH) resistance and high circulating levels of leptin. Leptin increased during fasting concomitantly with AMPK activation, which was inversely correlated with TOR activation. On the other hand, AMPK was directly correlated with an increase in PGC-1α and OXPHOS complexes contents. Dramatic changes in the activation and content of these molecules were observed during short-term refeeding. Leptin, AMPK activation, and PGC-1α/OXPHOS complexes contents decreased radically; whereas, TOR activation increased significantly. During long-term refeeding these molecules returned to basal levels. These results suggest that there is a relation among these components; thus, during fasting periods ATP-consuming biosynthetic pathways are repressed and alternative sources of ATP/energy are promoted, a phenomenon that is reversed during anabolic periods. These results provide novel insight on the control of metabolism and growth in the skeletal muscle of a non-mammalian species, suggesting that both processes in fish muscle are closely related and coordinated by a subset of common molecules. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Low dietary protein is associated with an increase in food intake and a decrease in the in vitro release of radiolabeled glutamate and GABA from the lateral hypothalamus.

    Science.gov (United States)

    White, B D; Du, F; Higginbotham, D A

    2003-12-01

    Moderately low-protein diets lead to a rapid increase in food intake and body fat. The increase in feeding is associated with a decrease in the concentration of serum urea nitrogen, suggesting that the low-protein-induced increase in food intake may be related to the decreased metabolism of nitrogen from amino acids. We hypothesized that low dietary protein would be associated with a decrease in the synaptic release of two nitrogen-containing neurotransmitters, GABA and glutamate, whose nitrogen can be derived from amino acids. In this study, we examined the effects of a low-protein diet (10% casein) in Sprague-Dawley rats on the in vitro release of 3H-GABA and 14C-glutamate from the lateral and medial hypothalamus. The low-protein diet increased food intake by about 25% after one day. After four days, the in vitro release of radiolabeled GABA and glutamate was assessed. The calcium-dependent, potassium-stimulated release of radiolabeled GABA and glutamate from the lateral hypothalamus was decreased in rats fed the low-protein diet. The magnitude of neurotransmitter release from the lateral hypothalamus inversely correlated with food intake. No dietary differences in the release of neurotransmitters from the medial hypothalamus were observed. These results support the contention that alterations in nitrogen metabolism are associated with low-protein-induced feeding.

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

    Science.gov (United States)

    Shabana, -; Hasnain, Shahida

    2016-06-01

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

  7. Leptin and glucocorticoid signaling pathways in the hypothalamus of female and male fructose-fed rats

    Directory of Open Access Journals (Sweden)

    Vojnović-Milutinović Danijela

    2014-01-01

    Full Text Available Alterations in leptin and glucocorticoid signaling pathways in the hypothalamus of male and female rats subjected to a fructose-enriched diet were studied. The level of expression of the key components of the leptin signaling pathway (neuropeptide Y /NPY/ and suppressor of cytokine signaling 3 /SOCS3/, and the glucocorticoid signaling pathway (glucocorticoid receptor /GR/, 11β-hydroxysteroid dehydrogenase type 1 /11βHSD1/ and hexose-6-phosphate dehydrogenase /H6PDH/ did not differ between fructose-fed rats and control animals of both genders. However, in females, a fructose-enriched diet provoked increases in the adiposity index, plasma leptin and triglyceride concentrations, and displayed a tendency to decrease the leptin receptor (ObRb protein and mRNA levels. In male rats, the fructose diet caused elevations in plasma non-esterified fatty acids and triglycerides, as well as in both plasma and hypothalamic leptin concentrations. Our results suggest that a fructose-enriched diet can induce hyperleptinemia in both female and male rats, but with a more pronounced effect on hypothalamic leptin sensitivity in females, probably contributing to the observed development of visceral adiposity. [Projekat Ministarstva nauke Republike Srbije, br. III41009

  8. The Influence of Thyroid Hormones on Leptin and Resistin Levels in Hyperthyroid Female Patients

    Directory of Open Access Journals (Sweden)

    Al-Hindawi Sahar H

    2018-01-01

    Full Text Available Background: Hyperthyroidism or thyrotoxicosis occurs due to excess release of thyroid hormone. These hormones regulate the body’s energy balance and have effects on adipokine level. There are several reports suggesting interrelation between adipokines (resistin and leptin with thyroid dysfunction. Objectives: This study was established to investigate the effect of thyroid hormones in hyperthyroidism state on the level of some adipokines, leptin and resistin; in comparison with control. Patients and Methods: The present study included 50 Iraqi female patients with hyperthyroidism with age ranged between 30-58 years and 30 healthy controls with age ranged between 30-53 years. Serum samples were collected from study groups. The levels of thyroid hormones (TSH, T4 and T3 were determined by using automated Chemiluminescence Immunoassay (CLIA analysis system. Detection of leptin hormone and resistin hormone levels in the serum were determined by an enzyme linked immunosorbent assay (ELISA kits. Results: The results revealed that serum leptin levels were significantly low (P<0.004 in hyperthyroid patient groups as compared to control, and there were significant negative correlations between T4 and leptin (P<0.0001; also, T3 and leptin (P<0.05. Resistin hormone level increased non-significantly (P˃0.05 than control level; and there was significant negative correlation between TSH and resistin (P<0.035. Conclusion: The study shows that there is complex interrelation between adipocytokines (leptin and resistin with thyroid gland and pituitary gland. Leptin levels were decreased in hyperthyroid patients than control and associated negatively with T4 and T3 levels, while resistin levels were increased non-significantly than control and associated negatively with TSH level. They affect each other in their physiological function in the human body.

  9. Assessment of leptin and some Antioxidants in Blood of Chronic Renal Failure Patients

    International Nuclear Information System (INIS)

    Ahmed, A.M.

    2004-01-01

    The aim of the present work is to study the effect of haemodialysis on the state of the antioxidants glutathione peroxidase (GPx) and vitamin C and the role of leptin hormone on the redox homeostasis in patients with chronic renal failure (CRF). This study was carried out on 25 patients (15 females and 10 males) with CRF,aged 19-55 years, in addition to 25 healthy control (10 females and 15 males). Patients were subjected to regular haemodialysis for 4 hours three times weekly and blood samples were collected before haemodialysis. In this study, plasma leptin was significantly increased in CRF group than normal control. Vitamin C and GPx were decreased significantly in CRF group in comparison with normal control. There was non-significant difference in serum leptin level between males and females in both control and patient groups. Patients showed significant lower body mass index (BMI) and albumin and higher cholesterol. In the control group, serum leptin levels showed significant positive correlation with BMI, while CRF group had significant negative correlation. In CRF group, serum leptin showed significant negative correlation with serum albumin and non-significant negative correlation with both creatinine and cholesterol. This is probably due to malnutrition status commonly occurs in renal failure. Serum leptin levels showed non-significant negative correlation between both GPx and Vitamin C in control group while in patient group, leptin showed significant positive correlation with GPx and vitamin C. In conclusion leptin acts on energy metabolism and plays a role in the modulation of cellular redox balance while the oxidative stress plays a role in many disease states. These diseases had increased incidence in uremia and particularly in haemodialysis

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

    Directory of Open Access Journals (Sweden)

    Hakan Uzun

    2015-01-01

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

  11. Calcineurin /NFAT activation-dependence of leptin synthesis and vascular growth in response to mechanical stretch

    Directory of Open Access Journals (Sweden)

    Nadia Soudani

    2016-09-01

    Full Text Available Background and Aims- Hypertension and obesity are important risk factors of cardiovascular disease. They are both associated with high leptin levels and have been shown to promote vascular hypertrophy, through the RhoA/ROCK and ERK1/2 phosphorylation. Calcineurin/NFAT activation also induces vascular hypertrophy by upregulating various genes. This study aimed to decipher whether a crosstalk exists between the RhoA/ROCK pathway, Ca+2/calcineurin/NFAT pathway, and ERK1/2 phosphorylation in the process of mechanical stretch-induced vascular smooth muscle cell (VSMC hypertrophy and leptin synthesis. Methods and Results- Rat portal vein (RPV organ culture was used to investigate the effect of mechanical stretch and exogenous leptin (3.1 nM on VSMC hypertrophy and leptin synthesis. Results showed that stretching the RPV significantly upregulated leptin secretion, mRNA and protein expression, which were inhibited by the calcium channel blocker nifedipine (10 μM, the selective calcineurin inhibitor FK506 (1 nM and the ERK1/2 inhibitor PD98059 (1 μM. The transcription inhibitor actinomycin D (0.1M and the translation inhibitor cycloheximide (1 mM significantly decreased stretch-induced leptin protein expression. Mechanical stretch or leptin caused an increase in wet weight changes and protein synthesis, considered as hypertrophic markers, while they were inhibited by FK506 (0.1 nM; 1 nM. In addition, stretch or exogenous leptin significantly increased calcineurin activity and MCIP1 expression whereas leptin induced NFAT nuclear translocation in VSMCs. Moreover, in response to stretch or exogenous leptin, the Rho inhibitor C3 exoenzyme (30 ng/mL, the ROCK inhibitor Y-27632 (10 μM, and the actin depolymerization agents Latrunculin B (50 nM and cytochalasin D (1 μM reduced calcineurin activation and NFAT nuclear translocation. ERK1/2 phosphorylation was inhibited by FK506 and C3. Conclusions- Mechanical stretch-induced VSMC hypertrophy and leptin

  12. Leptin and ghrelin in anadromous Arctic charr: cloning and change in expressions during a seasonal feeding cycle.

    Science.gov (United States)

    Frøiland, Eirik; Murashita, Koji; Jørgensen, Even Hjalmar; Kurokawa, Tadahide

    2010-01-01

    Anadromous (sea-migrating) Arctic charr (Salvelinus alpinus) display pronounced seasonal variations in food intake and growth and is an interesting model for studying mechanisms of appetite regulation. In this study cDNAs encoding for ghrelin (GHRL) and leptin (LEP) in Arctic charr were cloned, after which stomach GHRL and liver LEP mRNA expressions were examined by qPCR during a seasonal feeding cycle of semi-wild anadromous Arctic charr. The fish were captured as they returned from summer feeding in seawater and transferred to an indoor tank where they were fed in excess until October the year after. Growth rate was low in late winter, increased in late spring and reached a peak during summer, and then declined during autumn, when the fish became sexually mature. The changes in growth rate were associated with corresponding changes in the proportion of fish that had been eating at each sampling date, and whole body lipid status. Stomach GHRL mRNA expression was high in late winter, decreased to a nadir in mid-summer and increased again to a high level in early autumn. Liver LEP mRNA remained low during winter, spring and early summer, after which there was a gradual, 7-fold increase until October. The seasonal changes in ghrelin and leptin support a role of these hormones in the long-term regulation of energy homeostasis in the anadromous Arctic charr. It cannot be excluded, however, that the increase in liver leptin expression during autumn is related to sexual maturation.

  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. Korean Curcuma longa L. induces lipolysis and regulates leptin in adipocyte cells and rats

    Science.gov (United States)

    Song, Won-Yeong

    2016-01-01

    BACKGROUND/OBJECTIVES Turmeric (Curcuma longa L.) has been reported to have many biological functions including anti-obesity. Leptin, peptide hormone produced by adipocytes and its concentration is increased in proportion to the amount of the adipocytes. In the present study, we examined the effects of Korean turmeric on the regulation of adiposity and leptin levels in 3T3-L1 adipocytes and rats fed a high-fat and high-cholesterol diet. MATERIALS/METHODS Leptin secretion, free fatty acid and glycerol contents in 3T3-L1 adipocytes were measured after incubation of cells with turmeric for 24 hours. Rats were divided into four experimental groups: a normal diet group (N), a high-fat and high-cholesterol diet group (HF), a high-fat and high-cholesterol diet group supplemented with 2.5% turmeric extracts (TPA group) and a high-fat and high-cholesterol diet group supplemented with 5% turmeric extracts (TPB group). Serum samples were used for the measurement of leptin concentration. RESULTS Contents of free fatty acid and glycerol showed concentration dependent increase in response to turmeric extracts. Effects of turmeric extracts on reduction of lipid accumulation in 3T3-L1 cells were examined by Oil Red O staining. Treatment with turmeric extracts resulted in increased expression levels of adipose triglyceride lipase and hormone-sensitive lipase mRNA. The concentration of leptin from 3T3-L1 adipocytes was significantly decreased by turmeric. Proportional abdominal and epididymal fats weights of the turmeric 5% supplemented group, TPB has significantly decreased compared to the HF group. The serum levels of leptin in the TPA and TPB groups were significantly lower than those of the HF group. CONCLUSIONS Based on these results, we suggested that Korean turmeric may contribute to the decreasing of body fat and regulating leptin secretion. PMID:27698955

  15. [Serum leptin levels and soluble leptin receptors in female patients with anorexia nervosa].

    Science.gov (United States)

    Jiskra, J; Haluzík, M; Svobodová, J; Haluzíková, D; Nedvídková, J; Parízková, J; Kotrlíková, E

    2000-10-25

    Leptin action in peripheral tissues is enabled by an interaction with specific transmembrane receptors. Several of leptin receptor isoforms were identified, including soluble leptin receptor isoform structurally identical to extracellular domain of the the long leptin receptor isoform. The soluble receptor isoform is released to the circulation and acts probably as leptin-binding factor. The aim of our study was to measure serum concentrations of the soluble leptin receptor in patients with anorexia nervosa and in the control group of healthy women. Relationships of soluble leptin receptor levels to body mass index (BMI), body fat content, serum leptin, TNF-alpha and insulin levels were also studied. 16 patients with anorexia nervosa and 16 age-matched lean healthy women were included into the study. All of the subjects were measured and weighed, the body fat content was estimated from the skinfold thickness measurement. The blood for the determination of leptin, soluble leptin receptor and other hormonal parameters was obtained from all subjects after the overnight fasting. BMI, body fat content, serum leptin and insulin levels in patients with anorexia nervosa were significantly lower than in the control group (BMI: 14.98 +/- 2.32 vs. 22.21 +/- 2.48, p anorexia nervosa were significantly higher compared the to control group (24.67 +/- 8.3 U.ml-1 vs. 15.71 +/- 2.79 U.ml-1, p anorexia nervosa were significantly higher in comparison with the healthy subjects. Except of the negative correlation between serum soluble leptin receptor levels and BMI no statistically significant relationships between serum soluble leptin receptor and the rest of parameters studied were found.

  16. PPARγ ablation sensitizes proopiomelanocortin neurons to leptin during high-fat feeding.

    Science.gov (United States)

    Long, Lihong; Toda, Chitoku; Jeong, Jing Kwon; Horvath, Tamas L; Diano, Sabrina

    2014-09-01

    Activation of central PPARγ promotes food intake and body weight gain; however, the identity of the neurons that express PPARγ and mediate the effect of this nuclear receptor on energy homeostasis is unknown. Here, we determined that selective ablation of PPARγ in murine proopiomelanocortin (POMC) neurons decreases peroxisome density, elevates reactive oxygen species, and induces leptin sensitivity in these neurons. Furthermore, ablation of PPARγ in POMC neurons preserved the interaction between mitochondria and the endoplasmic reticulum, which is dysregulated by HFD. Compared with control animals, mice lacking PPARγ in POMC neurons had increased energy expenditure and locomotor activity; reduced body weight, fat mass, and food intake; and improved glucose metabolism when exposed to high-fat diet (HFD). Finally, peripheral administration of either a PPARγ activator or inhibitor failed to affect food intake of mice with POMC-specific PPARγ ablation. Taken together, our data indicate that PPARγ mediates cellular, biological, and functional adaptations of POMC neurons to HFD, thereby regulating whole-body energy balance.

  17. Modelling decreased food chain accumulation of HOCs due to strong sorption to carbonaceous materials and metabolic transformation

    NARCIS (Netherlands)

    Moermond, C.T.A.; Traas, T.P.; Roessink, I.; Veltman, K.; Hendriks, A.J.; Koelmans, A.A.

    2007-01-01

    The predictive power of bioaccumulation models may be limited when they do not account for strong sorption of organic contaminants to carbonaceous materials (CM) such as black carbon, and when they do not include metabolic transformation. We tested a food web accumulation model, including sorption

  18. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet

    NARCIS (Netherlands)

    Mars, M.; Graaf, de C.; Groot, de C.P.G.M.; Rossum, van C.T.M.; Kok, F.J.

    2006-01-01

    Objective: Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between

  19. The role of leptin in the regulation of energy balance and adiposity

    NARCIS (Netherlands)

    van Dijk, G

    2001-01-01

    Since its discovery, leptin (a 167-amino acid product of the OB gene) has quickly moved to the forefront as an important hormone for regulation of energy balance. It closes a feedback loop from adipose tissue to hypothalamic neuropeptide-containing neural circuitry involved in regulation of food

  20. Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet.

    NARCIS (Netherlands)

    Mars, M; Graaf, C de; Groot, C P G M de; Rossum, Caroline T M van; Kok, F J

    2006-01-01

    OBJECTIVE: Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between

  1. Running on Empty: Leptin Signaling in VTA Regulates Reward from Physical Activity.

    Science.gov (United States)

    Chen, Zuxin; Kenny, Paul J

    2015-10-06

    Hunger increases physical activity and stamina to support food-directed foraging behaviors, but underlying mechanisms are unclear. In this issue, Fernandes et al. (2015) show that disruption of leptin-regulated STAT3 signaling in midbrain dopamine neurons increases the rewarding effects of running in mice, which could explain the "high" experienced by endurance runners. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The effect of cumulative endurance exercise on leptin and adiponectin and their role as markers to monitor training load

    Directory of Open Access Journals (Sweden)

    SC Voss

    2016-01-01

    Full Text Available Leptin and adiponectin play an essential role in energy metabolism. Leptin has also been proposed as a marker for monitoring training load. So far, no studies have investigated the variability of these hormones in athletes and how they are regulated during cumulative exercises This study monitored leptin and adiponectin in 15 endurance athletes twice daily in the days before, during and after a 9-day simulated cycling stage race. Adiponectin significantly increased during the race (p=0.001 and recovery periods (p=0.002 when compared to the baseline, while leptin decreased significantly during the race (p<0.0001 and returned to baseline levels during the recovery period. lntra-individual variability was substantially lower than inter-individual variability for both hormones (leptin 34.1 vs. 53.5%, adiponectin 19% vs. 37.2%. With regards to exercise, this study demonstrated that with sufficient, sustained energy expenditure, leptin concentrations can decrease within the first 24 hours. Under the investigated conditions there also appears to be an optimal leptin concentration which ensures stable energy homeostasis, as there was no significant decrease over the subsequent race days. ln healthy endurance athletes the recovery of leptin takes 48-72 hours and may even show a supercompensation- like effect. For adiponectin, significant increases were observed within 5 days of commencing racing, with these elevated values failing to return to baseline levels after 3 days of recovery. Additionally, when using leptin and adiponectin to monitor training loads, establishing individual threshold values improves their sensitivity.

  3. Adipocyte differentiation and leptin expression

    DEFF Research Database (Denmark)

    Hwang, C S; Loftus, T M; Mandrup, S

    1997-01-01

    Adipose tissue has long been known to house the largest energy reserves in the animal body. Recent research indicates that in addition to this role, the adipocyte functions as a global regulator of energy metabolism. Adipose tissue is exquisitely sensitive to a variety of endocrine and paracrine ...... of energy intake and expenditure. The hormonal and transcriptional control of adipocyte differentiation is discussed, as is the role of leptin and other factors secreted by the adipocyte that participate in the regulation of adipose homeostasis.......Adipose tissue has long been known to house the largest energy reserves in the animal body. Recent research indicates that in addition to this role, the adipocyte functions as a global regulator of energy metabolism. Adipose tissue is exquisitely sensitive to a variety of endocrine and paracrine......, most notably those of the C/EBP and PPAR families, which combine to regulate each other and to control the expression of adipocyte-specific genes. One such gene, i.e. the obese gene, was recently identified and found to encode a hormone, referred to as leptin, that plays a major role in the regulation...

  4. Oral administration of O-2 lean, an anti-obesity herbal composition increased 5-HT metabolism, decreased food intake and body weight in overweight rats

    International Nuclear Information System (INIS)

    Bano, F.; Akhtar, N.; Haleem, D.J.

    2012-01-01

    Feeding behavior is complex processes controlled by the neruroendocrine system.5-HT play an important role in regulation of energy balance by suppressing food intake. Depletion of brain serotonin increase feeding behavior and develop obesity. Many serotoninergic compounds are available in market for the management of body weight. 02-Lean is an anti-obesity herbal formulation prepared by combination of different herbs. Oral administration of aqueous suspension of 02-Lean caused a significant decrease in body weight, food intake, and increase in whole brain 5-HT 5HIAA, tryptophan and plasma tryptophan in over weight rats treated with 0.096g/2ml 02-Lean in comparison to control group. (author)

  5. 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

  6. [Mechanism study on leptin resistance in lung cancer cachexia rats treated by Xiaoyan Decoction].

    Science.gov (United States)

    Zhang, Yun-Chao; Jia, Ying-Jie; Yang, Pei-Ying; Zhang, Xing; Li, Xiao-Jiang; Zhang, Ying; Zhu, Jin-Li; Sun, Yi-Yu; Chen, Jun; Duan, Hao-Guo; Guo, Hua; Li, Chao

    2014-12-01

    To study the leptin resistance mechanism of Xiaoyan Decoction (XD) in lung cancer cachexia (LCC) rats. An LCC rat model was established. Totally 40 rats were randomly divided into the normal control group, the LCC model group, the XD group, and the positive control group, 10 in each group. After LCC model was set up, rats in the LCC model group were administered with normal saline, 2 mL each time. Rats in the XD group were administered with XD at the daily dose of 2 mL. Those in the positive control group were administered with Medroxyprogesterone Acetate suspension (20 mg/kg) by gastrogavage at the daily dose of 2 mL. All medication lasted for 14 days. The general condition and tumor growth were observed. Serum levels of leptin and leptin receptor in the hypothalamus were detected using enzyme-linked immunosorbent assay. Contents of neuropeptide Y (NPY) and anorexia for genomic POMC were detected using real-time PCR technique. Serum leptin levels were lower in the LCC model group than in the normal control group with statistical significance (P XD group (P XD or Medroxyprogesterone Acetate could effectively reduce levels of leptin receptor with statistical significance (P XD group and the positive control group (P 0.05). There was statistical difference in POMC between the normal control group and the LCC model group (P XD group and the positive control group with statistical significance (P XD group (P XD could increase serum leptin levels and reduce leptin receptor levels in the hypothalamus. LCC could be improved by elevating NPY contents in the hypothalamus and reducing POMC contents, promoting the appetite, and increasing food intake from the periphery pathway and the central pathway.

  7. Triiodothyronine modulates the expression of leptin and adiponectin in 3T3-L1 adipocytes.

    Science.gov (United States)

    Oliveira, Miriane de; de Síbio, Maria Teresa; Olimpio, Regiane Marques Castro; Moretto, Fernanda Cristina Fontes; Luvizotto, Renata de Azevedo Melo; Nogueira, Celia Regina

    2015-01-01

    To study the effect of different doses of triiodothyronine on gene expression of the adipokines leptin and adiponectin, at different times, and to evaluate the difference in expression between the two adipokines in each group. 3T3-L1 adipocytes were incubated with triiodothyronine at physiological dose (10nM) and supraphysiological doses (100nM or 1,000nM), or without triiodothyronine (control, C) for 0.5, 6, or 24 hours. Leptin and adiponectin mRNA was detected using real-time polymerase chain reaction (RT-PCR). One-way analyses of variance, Tukey's test or Student's t test, were used to analyze data, and significance level was set at 5%. Leptin levels decreased in the 1,000nM-dose group after 0.5 hour. Adiponectin levels dropped in the 10nM-dose group, but increased at the 100nM dose. After 6 hours, both genes were suppressed in all hormone concentrations. After 24 hours, leptin levels increased at 10, 100 and 1,000nM groups as compared to the control group; and adiponectin levels increased only in the 100nM group as compared to the control group. These results demonstrated fast actions of triiodothyronine on the leptin and adiponectin expression, starting at 0.5 hour, at a dose of 1,000nM for leptin and 100nM for adiponectin. Triiodothyronine stimulated or inhibited the expression of adipokines in adipocytes at different times and doses which may be useful to assist in the treatment of obesity, assuming that leptin is increased and adiponectin is decreased, in obesity cases.

  8. Leptin in first trimester pregnancy serum

    DEFF Research Database (Denmark)

    Hedley, Paula; Pihl, Kasper; Krebs, Lone

    2009-01-01

    and its relation to fetal growth disturbances were examined in this study. The study is a case-control study with 36 small-for-gestational-age (SGA) (pregnancies and 108 appropriate-for-gestational-age (AGA) (> or =5th percentile) pregnancies. The groups were matched by maternal age...... maternal BMI. There was no significant difference in maternal serum leptin concentrations between SGA and AGA pregnancies. In conclusion, SGA pregnancies are not associated with a lower maternal serum leptin concentration in first trimester. The maternal serum leptin concentration is largely determined...

  9. 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

  10. A synthetic fragment of leptin increase hematopoietic stem cell population and improve its engraftment ability.

    Science.gov (United States)

    Dias, Carolina C; Nogueira-Pedro, Amanda; Tokuyama, Paula Yumi; Martins, Marta N C; Segreto, Helena Regina Comodo; Buri, Marcus V; Miranda, Antonio; Paredes-Gamero, Edgar J

    2015-07-01

    Several studies have shown the important actions of cytokine leptin that regulates food intake and energy expenditure. Additionally, the ability to modulate hematopoiesis has also been demonstrated. Previous reports have shown that some synthetic sequences of leptin molecules can activate leptin receptor. Herein, decapeptides encompassing amino acids from positions 98 to 122 of the leptin molecule were constructed to evaluate their effects on hematopoiesis. Among them, the synthetic peptide Lep(110-119)-NH2 (LEP F) was the only peptide that possessed the ability to increase the percentage of hematopoietic stem cells (HSC). Moreover, LEP F also produced an increase of granulocyte/macrophage colony-forming units and activated leptin receptor. Furthermore, LEP F also improves the grafting of HSC in bone marrow, but did not accelerate the recovery of bone marrow after ablation with 5-fluorouracil. These results show that LEP F is a positive modulator of the in vivo expansion of HSC and could be useful in bone marrow transplantation. © 2015 Wiley Periodicals, Inc.

  11. Oleogels, a promising structured oil for decreasing saturated fatty acid concentrations: Production and food-based applications.

    Science.gov (United States)

    Pehlivanoğlu, Halime; Demirci, Mehmet; Toker, Omer Said; Konar, Nevzat; Karasu, Salih; Sagdic, Osman

    2018-05-24

    Oils and fats are widely used in the food formulations in order to improve nutritional and some quality characteristics of food products. Solid fats produced from oils by hydrogenization, interesterification, and fractionation processes are widely used in different foodstuffs for these aims. In recent years, consumer awareness of relation between diet and health has increased which can cause worry about solid fat including products in terms of their high saturated fatty acid and trans fatty acid contents. Therefore, different attempts have been carried out to find alternative ways to produce solid fat with low saturated fatty acid content. One of the promising ways is using oleogels, structuring oils with oleogelators. In this review, history, raw materials and production methods of the oleogels and their functions in oleogel quality were mentioned. Moreover, studies related with oleogel usage in different products were summarized and positive and negative aspects of oleogel were also mentioned. Considering the results of the related studies, it can be concluded that oleogels can be used in the formulation of bakery products, breakfast spreads, margarines, chocolates and chocolate-derived products and some of the meat products.

  12. Alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age.

    Directory of Open Access Journals (Sweden)

    Gregory E Bigford

    Full Text Available Chronic spinal cord injury (SCI results in an accelerated trajectory of several cardiovascular disease (CVD risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF, resistin (Rstn, long-form leptin receptor (LepRb and suppressor of cytokine-3 (SOCS3 gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER stress and activation of the uncoupled protein response (UPR as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions.

  13. The effect of hemodialysis on the levels of plasma leptin and serum neuropeptide Y in uremia patients

    International Nuclear Information System (INIS)

    Li Hong; Liu Yan; Zhuang Wenqing

    2007-01-01

    To evaluate the changes of plasma leptin and serum neuropeptide Y (NPY) levels in uremia patients after hemodialysis and to discuss the efficient method on improving uremia malnutrition. 69 uremia patients were divided into 3 groups: Group A with 32 patients using low- flux cellulosic dialyzer, Group B with 21 patients using low-flux polysulfone dialyzer(F6), and Group C with 16 patients using high-flux polysulfone dialyzer(F60) and blood dialyzer. 18 healthy volunteers were chosen as the control group. The plasma leptin and serum NPY levels were detected by RIA in uremia patients before and after dialysis and in control group. Compared with control, all uremia patients had obviously higher leptin and NPY levels before dialysis (P<0.01); Leptin and NPY levels in group A and B did not change after dialysis. The leptin levels were significantly decreased in group C after dialysis (P<0.05), but NPY levels did not change. There was no correlation between higher levels of leptin and NPY in uremia patients. They could not be cleared by hemodialysis alone. Hemo-filtration with high flux polysulfone dialyzer could increase the clearance efficiency of leptin and improve nutritional conditions for uremia patients. (authors)

  14. PF-05231023, a long-acting FGF21 analogue, decreases body weight by reduction of food intake in non-human primates.

    Science.gov (United States)

    Thompson, W Clayton; Zhou, Yingjiang; Talukdar, Saswata; Musante, Cynthia J

    2016-08-01

    PF-05231023, a long-acting FGF21 analogue, is a promising potential pharmacotherapy for the treatment of obesity and associated comorbidities. Previous studies have shown the potential of FGF21 and FGF21-like compounds to decrease body weight in mice, non-human primates, and humans; the precise mechanisms of action remain unclear. In particular, there have been conflicting reports on the degree to which FGF21-induced weight loss in non-human primates is attributable to a decrease in food intake versus an increase in energy expenditure. Here, we present a semi-mechanistic mathematical model of energy balance and body composition developed from similar work in mice. This model links PF-05231023 administration and washout to changes in food intake, which in turn drives changes in body weight. The model is calibrated to and compared with recently published data from cynomolgus macaques treated with PF-05231023, demonstrating its accuracy in describing pharmacotherapy-induced weight loss in these animals. The results are consistent with the hypothesis that PF-05231023 decreases body weight in cynomolgus macaques solely by a reduction in food intake, with no direct effect on energy expenditure.

  15. High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Firas Alhasson

    2018-07-01

    Full Text Available High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell activation and tubular inflammation that showed accelerated NASH phenotype and oxidative stress in the liver. Results showed that NAFLD kidneys had significant increases in α-SMA, a marker of mesangial cell activation, miR21 levels, tyrosine nitration and renal inflammation while they were significantly decreased in leptin and p47 phox knockout mice. Micro RNA21 knockout mice showed decreased tubular immunotoxicity and proinflammatory mediator release. Mechanistically, use of NOX2 siRNA or apocynin,phenyl boronic acid (FBA, DMPO or miR21 antagomir inhibited leptin primed-miR21-mediated mesangial cell activation in vitro suggesting a direct role of leptin-mediated NOX-2 in miR21-mediated mesangial cell activation. Finally, JAK-STAT inhibitor completely abrogated the mesangial cell activation in leptin-primed cells suggesting that leptin signaling in the mesangial cells depended on the JAK-STAT pathway. Taken together the study reports a novel mechanistic pathway of leptin-mediated renal inflammation that is dependent on NOX-2-miR21 axis in ectopic manifestations underlying NAFLD-induced co-morbidities. Keywords: Leptin, NOX-2, NADPH, Mesangial cells, miR21, Oxidative stress, NAFLD, JAK/STAT, siRNA

  16. Pivotal role of leptin in insulin effects

    Directory of Open Access Journals (Sweden)

    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.

  17. Polymorphisms in the bovine leptin promoter associated with serum leptin concentration, growth, feed intake, feeding behavior, and measures of carcass merit.

    Science.gov (United States)

    Nkrumah, J D; Li, C; Yu, J; Hansen, C; Keisler, D H; Moore, S S

    2005-01-01

    Leptin is the hormone product of the obese gene synthesized and secreted predominantly by white adipocytes. It functions as a lipostatic signal regulating BW, food intake, energy expenditure, reproduction, and certain immune system functions. Although previous studies have identified polymorphisms in the coding regions of the leptin gene in cattle that show considerable associations with feed intake, milk quality and quantity, and carcass fatness, no such associations have been reported for the leptin promoter. The current study reports associations between SNP in the 5' untranslated promoter region of the bovine leptin gene with serum leptin concentration, growth, BW, feed intake, feeding behavior, and carcass merit in hybrid cattle (n = 150). The study showed that animals with the TT genotype of a less frequent cytosine/thymine (C/ T) substitution (UASMS2; frequency of thymine allele equals 0.21) detected at position 528 in the bovine leptin promoter (GenBank Accession No. AB070368) show 48 and 39% increases in serum leptin concentration (P < 0.001), 39 and 31% increases in backfat thickness (P < 0.001), and 13 and 9% increase in marbling score (P = 0.01), compared with CC or CT genotypes, respectively. Animals with the TT genotype also show significantly higher feed intake (P < 0.001), growth rate, metabolic BW (P < 0.05), and live weight at slaughter (P < 0.10). Animals with the GG genotype of a more frequent cytosine/guanine (C/G) substitution (UASMS3; frequency of G allele equals 0.59) at position 1759 in the bovine leptin promoter (GenBank Accession No. AB070368) also show higher feed intake (P = 0.001), growth rate (P < 0.10), and BW (P < 0.01). The thymine allele of UASMS2 and the guanine allele of UASMS3 were separately associated with higher feeding duration (P < 0.05). The two SNP show significant linkage disequilibrium and could also be relevant in predicting other characteristics, such as milk yield and quality in cattle. These results, however

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

    DEFF Research Database (Denmark)

    Scholze, Alexandra; Tepel, Martin

    2007-01-01

    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 by stimulat......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......, 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...... concentration is an independent risk factor for mortality in these patients....

  19. Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development

    DEFF Research Database (Denmark)

    Petersen, Y. M.; Hartmann, B.; Holst, Jens Juul

    2003-01-01

    increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P anorexia (34 +/- 5 pmol/L, P ... in these pigs. We conclude that the introduction of enteral feeding transiently increases plasma GLP-2 concentrations and decreases small intestinal GLP-2R mRNA levels during pig development. GLP-2 may play a role in the growth of the small intestine around birth and weaning via a response to enteral nutrition....

  20. Changes in plasma ghrelin and leptin levels in patients with peptic ulcer and gastritis following eradication of Helicobacter pylori infection.

    Science.gov (United States)

    Kasai, Chika; Sugimoto, Kazushi; Moritani, Isao; Tanaka, Junichiro; Oya, Yumi; Inoue, Hidekazu; Tameda, Masahiko; Shiraki, Katsuya; Ito, Masaaki; Takei, Yoshiyuki; Takase, Kojiro

    2016-10-04

    Helicobacter pylori (H. pylori) infection and eradication therapy have been known to influence gastric ghrelin and leptin secretion, which may lead to weight gain. However, the exact relationship between plasma ghrelin/leptin levels and H. pylori infection has remained controversial. The aim of this study was to investigate plasma ghrelin and leptin levels in H. pylori-positive and -negative patients, to compare the two levels of the hormones before and after H. pylori eradication, and to examine the correlation between body mass index (BMI) and active ghrelin or leptin levels, as well as that between atrophic pattern and active ghrelin or leptin levels. Seventy-two H. pylori-positive patients who underwent upper gastrointestinal endoscopy, 46 diagnosed as having peptic ulcer and 26 as atrophic gastritis, were enrolled. Control samples were obtained from 15 healthy H. pylori-negative volunteers. The extent of atrophic change of the gastric mucosa was assessed endoscopically. Body weight was measured and blood was collected before and 12 weeks after H. pylori eradication therapy. Blood samples were taken between 8 and 10 AM after an overnight fast. Plasma ghrelin levels were significantly lower in H. pylori-positive patients than in H. pylori-negative patients. In particular, plasma active ghrelin levels were significantly lower in patients with gastritis compared with patients with peptic ulcer. Plasma ghrelin levels decreased after H. pylori eradication in both peptic ulcer and gastritis patients, while plasma leptin levels increased only in peptic ulcer patients. Plasma leptin levels and BMI were positively correlated, and active ghrelin levels and atrophic pattern were weakly negatively correlated in peptic ulcer patients. H. pylori infection and eradication therapy may affect circulating ghrelin/leptin levels. This finding suggests a relationship between gastric mucosal injury induced by H. pylori infection and changes in plasma ghrelin and leptin levels.

  1. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

    Science.gov (United States)

    Martins, Ana D; Moreira, Ana C; Sá, Rosália; Monteiro, Mariana P; Sousa, Mário; Carvalho, Rui A; Silva, Branca M; Oliveira, Pedro F; Alves, Marco G

    2015-09-01

    Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Circulating leptin in patients with anorexia nervosa, bulimia nervosa or binge-eating disorder: relationship to body weight, eating patterns, psychopathology and endocrine changes.

    Science.gov (United States)

    Monteleone, P; Di Lieto, A; Tortorella, A; Longobardi, N; Maj, M

    2000-05-15

    A decreased production of leptin has been reported in women with anorexia nervosa (AN) and has been attributed merely to the patients' reduced body fat mass. The extent to which eating patterns, purging behaviors, psychopathology and endocrine changes may contribute to the genesis of leptin alterations has not been deeply investigated. Therefore, we measured plasma levels of leptin, glucose and other hormones in three groups of eating disorder patients with different body weight (BW), eating patterns and purging behaviors. Sixty-seven women, 21 with AN, 32 with bulimia nervosa (BN), 14 with binge-eating disorder (BED) and 25 healthy females volunteered for the study. We found that circulating leptin was significantly reduced in AN and BN patients, but significantly enhanced in women with BED. In anorexics, plasma glucose was decreased, whereas plasma cortisol was enhanced; blood concentrations of 17beta-estradiol and prolactin (PRL) were reduced in both AN, BN and BED patients. In all subject groups, a strong positive correlation emerged between plasma levels of leptin and the subjects' BW or body mass index, but not between leptin and psychopathological measures, plasma glucose, cortisol, PRL and 17beta-estradiol. Since leptin was reduced in both underweight anorexics and normal weight bulimics, but increased in overweight BED women, who compulsively binge without engaging in compensatory behaviors, we suggest that factors other than BW may play a role in the determination of leptin changes in eating disorders.

  3. 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.

  4. Leptin responsiveness to energy restriction: genetic variation in the leptin receptor gene.

    Science.gov (United States)

    Mars, Monica; van Rossum, Caroline T M; de Graaf, Cees; Hoebee, Barbara; De Groot, Lisette C P G M; Kok, Frans J

    2004-03-01

    Serum leptin concentrations are an important afferent signal in energy balance homeostasis. It has been speculated that the leptin responsiveness to energy restriction is affected by the functionality of the leptin receptor. The purpose of this analysis was to explore the effect of polymorphisms in the LEPR gene on the acute decline in leptin after 4 days of 65% energy restriction. Leptin concentrations of the study group (n = 44; all men) declined by 2.3 +/- 1.5 micro g/L [-39.4% (95% confidence interval: -43.6 to -34.9)]. Leptin responses did not statistically differ between noncarriers and carriers of three mutant variants of the polymorphisms: Lys109/Lys109 (-41.4%) vs. Arg109/+ (-37.0%) (p = 0.33); Gln223/Gln223 (-41.5%) vs. Arg223/+ (-37.8%) (p = 0.40); Lys656/Lys656 (-39.5%) vs. Asn656/+ (-39.3%) (p = 0.96). No effect of the assessed polymorphisms in the LEPR gene on the acute decline in leptin after energy restriction was observed. Power calculations are provided for future studies on the leptin responsiveness to energy restriction.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. A work-for-food enrichment program increases exploration and decreases stereotypies in four species of bears.

    Science.gov (United States)

    Wagman, Jason D; Lukas, Kristen E; Dennis, Patricia M; Willis, Mark A; Carroscia, Joe; Gindlesperger, Curt; Schook, Mandi W

    2018-01-01

    Zoo-housed bears are prone to exhibiting stereotypic behaviors, generally considered indicators of negative welfare. We explored the effects of a variable-time feeding enrichment schedule on behavioral indicators of welfare in four bear species at Cleveland Metroparks Zoo. We distributed the diets of eight bears in one of five enrichment items, for two consecutive days each, and monitored behavior throughout the day. In Experiment 1, we compared variable-time to fixed-time presentation of enrichment over two, 10-day periods. Overall, bears performed more exploratory behavior when enriched (p enrichment was associated with a greater increase in exploratory behavior than fixed-time enrichment when compared to baseline (p enrichment were also associated with similar decreases in abnormal behavior compared to baseline. For Experiment 2, we tested habituation to enrichment over 30 days using multiple items and a semi-variable presentation schedule. Again during the enrichment period, bears exhibited increased exploratory behavior (p enrichment period for these behaviors. Collectively, these results suggest that daily, variable-schedule feeding enrichment, with intermittent presentation of unique enrichment items, increases behavioral indicators of positive welfare and decreases behavioral indicators of negative welfare. © 2018 Wiley Periodicals, Inc.

  8. To eat or not to eat: ontogeny of hypothalamic feeding controls and a role for leptin in modulating life-history transition in amphibian tadpoles.

    Science.gov (United States)

    Bender, Melissa Cui; Hu, Caroline; Pelletier, Chris; Denver, Robert J

    2018-03-28

    Many animal life histories entail changing feeding ecology, but the molecular bases for these transitions are poorly understood. The amphibian tadpole is typically a growth and dispersal life-history stage. Tadpoles are primarily herbivorous, and they capitalize on growth opportunities to reach a minimum body size to initiate metamorphosis. During metamorphic climax, feeding declines, at which time the gastrointestinal (GI) tract remodels to accommodate the carnivorous diet of the adult frog. Here we show that anorexigenic hypothalamic feeding controls are absent in the tadpole, but develop during metamorphosis concurrent with the production of the satiety signal leptin. Before metamorphosis there is a large increase in leptin mRNA in fat tissue. Leptin receptor mRNA increased during metamorphosis in the preoptic area/hypothalamus, the key brain region involved with the control of food intake and metabolism. This corresponded with an increase in functional leptin receptor, as evidenced by induction of socs3 mRNA and phosphorylated STAT3 immunoreactivity, and suppression of feeding behaviour after injection of recombinant frog leptin. Furthermore, we found that immunoneutralization of leptin in tadpoles at metamorphic climax caused them to resume feeding. The absence of negative regulation of food intake in the tadpole allows the animal to maximize growth prior to metamorphosis. Maturation of leptin-responsive neural circuits suppresses feeding during metamorphosis to facilitate remodelling of the GI tract. © 2018 The Author(s).

  9. Hypothalamic mTOR signaling regulates food intake.

    Science.gov (United States)

    Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

    2006-05-12

    The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

  10. The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

    Science.gov (United States)

    Akyol, Murat; Demir, Leyla; Alacacioglu, Ahmet; Ellidokuz, Hülya; Kucukzeybek, Yuksel; Yildiz, Yasar; Gumus, Zehra; Bayoglu, Vedat; Yildiz, Ibrahim; Salman, Tarık; Varol, Umut; Kucukzeybek, Betul; Demir, Lutfiye; Dirican, Ahmet; Sutcu, Recep; Tarhan, Mustafa Oktay

    2016-01-01

    A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone. © 2015 S. Karger AG, Basel.

  11. Frequency of soup intake and amount of dietary fiber intake are inversely associated with plasma leptin concentrations in Japanese adults.

    Science.gov (United States)

    Kuroda, Motonaka; Ohta, Masanori; Okufuji, Tatsuya; Takigami, Chieko; Eguchi, Masafumi; Hayabuchi, Hitomi; Ikeda, Masaharu

    2010-06-01

    Previous studies have shown that the intake of soup negatively correlates with the body mass index (BMI), suggesting that soup intake reduces the risk of obesity. In this study, to clarify the association of the intake of soup and various nutrients with plasma leptin concentration, a cross-sectional study on 504 Japanese adults aged 20-76 years (103 men and 401 women) was performed. The intake of soup and various nutrients was investigated by food frequency questionnaires. Plasma leptin concentration was measured in fasting blood by radioimmunoassay. The correlation was analyzed by multiple regression analysis. The average frequency of soup intake was 7.6 times/week. The average plasma leptin concentration was 7.76 ng/ml. After adjusting the confounding factors, the frequency of soup intake has a significant inverse association with plasma leptin concentration. Among the macronutrients, only dietary fiber intake negatively correlated with plasma leptin concentration after the adjustment for potential confounding factors. These results suggest that the intakes of soup and dietary fiber were negatively correlated with plasma leptin concentration in Japanese adults. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity

    Directory of Open Access Journals (Sweden)

    Natália P. Castro

    2017-02-01

    Full Text Available Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM% was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI, weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin (p = 0.001 and pre-pregnancy BMI (p < 0.001; adj. R2 = 0.19 were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

  13. The Relationship between Maternal Plasma Leptin and Adiponectin Concentrations and Newborn Adiposity.

    Science.gov (United States)

    Castro, Natália P; Euclydes, Verônica V; Simões, Fernanda A; Vaz-de-Lima, Lourdes R A; De Brito, Cyro A; Luzia, Liania A; Devakumar, Delan; Rondó, Patrícia H C

    2017-02-23

    Increased maternal blood concentrations of leptin and decreased adiponectin levels, which are common disturbances in obesity, may be involved in offspring adiposity by programming fetal adipose tissue development. The aim of this study was to assess the relationship between maternal leptin and adiponectin concentrations and newborn adiposity. This was a cross-sectional study involving 210 healthy mother-newborn pairs from a public maternity hospital in São Paulo, Brazil. Maternal blood samples were collected after delivery and leptin and adiponectin concentrations were measured by enzyme-linked immunosorbent assay. Newborn body composition was estimated by air displacement plethysmography. The association between maternal leptin and adiponectin concentrations and newborn adiposity (fat mass percentage, FM%) was evaluated by multiple linear regression, controlling for maternal age, socioeconomic status, parity, pre-pregnancy body mass index (BMI), weight gain, gestational age, and newborn age at the time of measurement. No relationship was found between maternal leptin and FM% of male or female newborn infants. Maternal adiponectin ( p = 0.001) and pre-pregnancy BMI ( p < 0.001; adj. R ² = 0.19) were positively associated with FM% of newborn males, indicating that maternal adiponectin is involved in fetal fat deposition in a sex-specific manner. Large-scale epidemiological, longitudinal studies are necessary to confirm our results.

  14. Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

    Science.gov (United States)

    Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

    2011-02-25

    Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Sleep restriction is associated with increased morning plasma leptin concentrations, especially in women.

    Science.gov (United States)

    Simpson, Norah S; Banks, Siobhan; Dinges, David F

    2010-07-01

    We evaluated the effects of sleep restriction on leptin levels in a large, diverse sample of healthy participants, while allowing free access to food. Prospective experimental design. After 2 nights of baseline sleep, 136 participants (49% women, 56% African Americans) received 5 consecutive nights of 4 hours time in bed (TIB). Additionally, one subset of participants received 2 additional nights of either further sleep restriction (n = 27) or increased sleep opportunity (n = 37). Control participants (n = 9) received 10 hr TIB on all study nights. Plasma leptin was measured between 10:30 a.m. and 12:00 noon following baseline sleep, after the initial sleep-restriction period, and after 2 nights of further sleep restriction or recovery sleep. Leptin levels increased significantly among sleep-restricted participants after 5 nights of 4 hr TIB (Z = -8.43, p women compared to men (Z = -4.77, p restriction (p restriction with ad libitum access to food significantly increases morning plasma leptin levels, particularly among women.

  16. Melatonin Absence Leads to Long-Term Leptin Resistance and Overweight in Rats

    Science.gov (United States)

    Buonfiglio, Daniella; Parthimos, Rafaela; Dantas, Rosana; Cerqueira Silva, Raysa; Gomes, Guilherme; Andrade-Silva, Jéssica; Ramos-Lobo, Angela; Amaral, Fernanda Gaspar; Matos, Raphael; Sinésio, José; Motta-Teixeira, Lívia Clemente; Donato, José; Reiter, Russel J.; Cipolla-Neto, José

    2018-01-01

    Melatonin (Mel), a molecule that conveys photoperiodic information to the organisms, is also involved in the regulation of energy homeostasis. Mechanisms of action of Mel in the energy balance remain unclear; herein we investigated how Mel regulates energy intake and expenditure to promote a proper energy balance. Male Wistar rats were assigned to control, control + Mel, pinealectomized (PINX) and PINX + Mel groups. To restore a 24-h rhythm, Mel (1 mg/kg) was added to the drinking water exclusively during the dark phase for 13 weeks. After this treatment period, rats were subjected to a 24-h fasting test, an acute leptin responsiveness test and cold challenge. Mel treatment reduced food intake, body weight, and adiposity. When challenged to 24-h fasting, Mel-treated rats also showed reduced hyperphagia when the food was replaced. Remarkably, PINX rats exhibited leptin resistance; this was likely related to the capacity of leptin to affect body weight, food intake, and hypothalamic signal-transducer and activator of transcription 3 phosphorylation, all of which were reduced. Mel treatment restored leptin sensitivity in PINX rats. An increased hypothalamic expression of agouti-related peptide (Agrp), neuropeptide Y, and Orexin was observed in the PINX group while Mel treatment reduced the expression of Agrp and Orexin. In addition, PINX rats presented lower UCP1 protein levels in the brown adipose tissue and required higher tail vasoconstriction to get a proper thermogenic response to cold challenge. Our findings reveal a previously unrecognized interaction of Mel and leptin in the hypothalamus to regulate the energy balance. These findings may help to explain the high incidence of metabolic diseases in individuals exposed to light at night. PMID:29636725

  17. Leptin stimulates aromatase in the growth plate: limiting catch-up growth efficiency.

    Science.gov (United States)

    Masarwi, Majdi; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

    2018-06-01

    Catch-up growth (CUG) in childhood is defined as periods of growth acceleration, after the resolution of growth attenuation causes, bringing the children back to their original growth trajectory. Sometimes, however, CUG is incomplete, leading to permanent growth deficit and short stature. The aim of this study was to investigate the mechanisms that limit nutritional-CUG. Specifically, we focused on the crosstalk between leptin, increased by re-feeding, and sex hormones, which increase with age. In vivo studies were performed in young male Sprague Dawley rats fed ad libitum or subjected to 10/36 days of 40% food restriction followed by 90-120 days of re-feeding. In vitro studies were performed on ATDC5 cells. Analyses of mRNA and protein levels were done using qPCR and Western blot, respectively. CUG was complete in body weight and humerus length in animals that were food-restricted for 10 days but not for those food-restricted for 36 days. In vitro studies showed that leptin significantly increased aromatase gene expression and protein level as well as the expression of estrogen and leptin receptors in a dose- and time-dependent manner. The effect of leptin on aromatase was direct and was mediated through the MAPK/Erk, STAT3 and PI3K pathways. The crosstalk between leptin and aromatase in the growth plate suggests that re-feeding during puberty may lead to increased estrogen level and activity, and consequently, irreversible premature epiphyseal growth plate closure. These results may have important implications for the development of novel treatment strategies for short stature in children. © 2018 Society for Endocrinology.

  18. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  19. 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.

  20. Molecular characterization of leptin (obese) gene in domesticated ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-03-06

    Mar 6, 2009 ... National Bureau of Animal Genetic Resources, Karnal, ... Leptin is obesity gene involved in production and reproduction traits in domestic animals. In the ..... leptin concentration, growth, feed intake, feeding behavior, and.

  1. Effect of Raised Body Fat on Vitamin D, Leptin and Bone Mass

    International Nuclear Information System (INIS)

    Fatima, S. S.; Alam, F.

    2015-01-01

    Objectives: To estimate leptin, vitamin D and bone mineral density levels in individuals with high fat mass, and to assess any correlation. Methods: The cross-sectional study was conducted at the Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, and Aga Khan University, Karachi, from August 2012 to July 2014, and comprised healthy male volunteers between the ages of 18-60 years. Body fat percentage was determined using bioelectrical impedance analysis and the participants were classified as: Group A (15-21.9); Group B (22-27.9); and Group C (>28). Bone mineral density was calculated by ultrasound bone densitometer (T-score between +1 and -1 considered normal). Enzyme-linked immunosorbent assay kits were used to determine the levels of vitamin D and leptin. SPSS 19 was used for statistical analysis. Results: A total of 132 male subjects participated in this study, with each of the 3 groups having 44(33.3 percent). Despite all groups having low Vitamin D, a marked decrease was observed in group C compared to groups A and B (p <0.018). Bone mineral density T-score was <-1; total calcium was within normal range in all three groups. Serum leptin was raised in Group C compared to group A and B (p=0.03). Body fat percentage was negatively associated with vitamin D (p=0.004; r = -0.351), while it was positively correlated with leptin (p =0.038; r = 0.256). Conclusion: Excess of body fat percentage led to decreased vitamin D and raised leptin. However, bone mineral density and calcium levels were within normal range, suggesting that other factors might have played a role in maintaining bone mass in obese individuals, such as leptin. (author)

  2. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    International Nuclear Information System (INIS)

    Mohamed, S.K.

    2010-01-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  3. The Role of Serum Leptin and IL-6 Levels in Post Viral Hepatitis Cirrhotic patients

    Energy Technology Data Exchange (ETDEWEB)

    Mohamed, S.K., E-mail: Safaa-K-mohamed@hotmail.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P. O. Box:29 Nasr City, Cairo (Egypt)

    2010-07-01

    Chronic liver disease is characterized by numerous metabolic alterations resulting in the clinical picture of malnutrition or even cachexia and contributing to complications such as hepatic encephalopathy and ascites. Leptin is a hormone that plays an important role in regulating energy intake and expenditure including appetite and metabolism. Interleukin-6 (IL-6), on the other hand, is generally considered to be one of the important cytokines that regulate immunologic and metabolic actions. The aim of the present study was to investigate serum leptin and IL-6 levels in liver cirrhosis, as well as to determine their levels in relation to liver functions and lipid profile. This study was conducted on 25 patients with post- viral hepatic cirrhosis compared to 20 healthy matched individuals served as controls with the same age and sex. The severity of the disease assessed with Child-Pugh criteria yielded 8 patients (3 women, 5 men) with stage A, 10 patients (4 women, 6 men) with stage B and 7 patients (2 women, 5 men) with stage C. Compared to controls, body mass index (BMI) was decreased and reached statistical significance in group C liver cirrhosis (P< 0.05). Also, serum leptin level was highly significantly decreased in the three groups, while IL-6 level showed highly significant increase. Leptin level negatively correlated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin and positively correlated with serum albumin, triglycerides (TG), cholesterol and low density lipoprotein (LDL). In contrast, serum IL-6 level positively correlated with parameters of liver functions and negatively correlated with parameters of lipid profile. Additionally, there was highly significant negative correlation between serum leptin and IL-6 levels (P < 0.001) in post-hepatic cirrhotic patients. We concluded that leptin and IL-6 have important role in diagnosis and prognosis of patients with post-hepatic liver cirrhosis

  4. High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell.

    Science.gov (United States)

    Lin, Xian-Hua; Wang, Hui; Wu, Dan-Dan; Ullah, Kamran; Yu, Tian-Tian; Ur Rahman, Tanzil; Huang, He-Feng

    2017-07-01

    Obesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children.

    Science.gov (United States)

    Besbas, Nesrin; Ozaltin, Fatih; Coşkun, Turgay; Ozalp, Sila; Saatçi, Umit; Bakkaloğlu, Aysin; El Nahas, A Meguid

    2003-12-01

    Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin

  6. Leptin promotes osteoblast differentiation and mineralization of primary cultures of vascular smooth muscle cells by inhibiting glycogen synthase kinase (GSK)-3{beta}

    Energy Technology Data Exchange (ETDEWEB)

    Zeadin, Melec G.; Butcher, Martin K.; Shaughnessy, Stephen G. [Department of Medicine, McMaster University, Hamilton, ON (Canada); Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (Canada); Werstuck, Geoff H., E-mail: Geoff.Werstuck@taari.ca [Department of Medicine, McMaster University, Hamilton, ON (Canada); Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (Canada)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Leptin promotes osteoblast differentiation of primary smooth muscle cells. Black-Right-Pointing-Pointer Leptin regulates the expression of genes involved in osteoblast differentiation. Black-Right-Pointing-Pointer Constitutively active GSK-3{beta} attenuates leptin-induced osteoblast differentiation. Black-Right-Pointing-Pointer This suggests that leptin signals through GSK-3{beta} to promote osteoblast differentiation. -- Abstract: In this study, we begin to investigate the underlying mechanism of leptin-induced vascular calcification. We found that treatment of cultured bovine aortic smooth muscle cells (BASMCs) with leptin (0.5-4 {mu}g/ml) induced osteoblast differentiation in a dose-dependent manner. Furthermore, we found that leptin significantly increased the mRNA expression of osteopontin and bone sialoprotein, while down-regulating matrix gla protein (MGP) expression in BASMCs. Key factors implicated in osteoblast differentiation, including members of the Wnt signaling pathway, were examined. Exposure to leptin enhanced phosphorylation of GSK-3{beta} on serine-9 thereby inhibiting activity and promoting the nuclear accumulation of {beta}-catenin. Transfection of BASMCs with an adenovirus that expressed constitutively active GSK-3{beta} (Ad-GSK-3{beta} S9A) resulted in a >2-fold increase in GSK-3{beta} activity and a significant decrease in leptin-induced alkaline phosphatase (ALP) activity. In addition, qRT-PCR analysis showed that GSK-3{beta} activation resulted in a significant decrease in the expression of osteopontin and bone sialoprotein, but a marked increase in MGP mRNA expression. When taken together, our results suggest a mechanism by which leptin promotes osteoblast differentiation and vascular calcification in vivo.

  7. Circulating Ghrelin, Leptin, and Soluble Leptin Receptor Concentrations and Cardiometabolic Risk Factors in a Community-Based Sample

    OpenAIRE

    Ingelsson, Erik; Larson, Martin G.; Yin, Xiaoyan; Wang, Thomas J.; Meigs, James B.; Lipinska, Izabella; Benjamin, Emelia J.; Keaney, John F.; Vasan, Ramachandran S.

    2008-01-01

    Context: The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown.

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

    African Journals Online (AJOL)

    The mutation in leptin receptor (LEPR) gene causes splicing abnormality that resulted in truncated receptor, aberrant signal transduction, leptin resistance, and obesity. This study aims to determine the association of LEPR gene polymorphisms, rs1137100 and rs1137101, on phenotype and leptin level between obese and ...

  9. Role of leptin in energy expenditure : The hypothalamic perspective

    NARCIS (Netherlands)

    Pandit, R.; Beerens, S.; Adan, R. A.H.

    2017-01-01

    The adipocyte-derived hormone leptin is a peripheral signal that informs the brain about the metabolic status of an organism. Although traditionally viewed as an appetite-suppressing hormone, studies in the past decade have highlighted the role of leptin in energy expenditure. Leptin has been shown

  10. 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 ...

  11. 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 + ...

  12. Effect of nutritional recovery with soybean flour diet on body composition, energy balance and serum leptin concentration in adult rats

    Directory of Open Access Journals (Sweden)

    Boschero Antonio C

    2009-08-01

    Full Text Available Abstract Background Malnutrition in early life is associated with obesity in adulthood and soybean products may have a beneficial effect on its prevention and treatment. This study evaluated body composition, serum leptin and energy balance in adult rats subjected to protein restriction during the intrauterine stage and lactation and recovering on a soybean flour diet. Methods Five groups of the Wistar strain of albino rats were used: CC, offspring born to and suckled by mothers fed a control diet and fed the same diet after weaning; CS, offspring born to and suckled by mothers fed a control diet and fed a soybean diet with 17% protein after weaning; LL, offspring of mothers fed a low protein diet and fed the same diet after weaning; LC, offspring of mothers fed a low protein diet, but fed a control diet after weaning; LS, offspring of mothers fed a low protein diet, but fed a soybean diet with 17% protein after weaning. Food intake, body, perirenal and retroperitoneal adipose tissue were measured in grams. Leptin was quantified using the Enzyme Linked Immuno Sorbent Assay (ELISA and insulin by radioimmunoassay (RIA. Carcass composition was determined by chemical methods and energy expenditure was calculated by the difference between energy intake and carcass energy gain. Data were tested by analysis of variance (ANOVA. Results The LC and LS groups had higher energetic intake concerning body weight, lower energy expenditure, proportion of fat carcass and fat pads than CC and CS groups. The LS group showed reduced body weight gain and lower energy efficiency, which was reflected in less energy gain as protein and the proportion of carcass protein, and lower energy gain as lipid than in the LC groups, although both groups had eaten the same amount of diet and showed equal energy expenditure. Serum leptin did not differ among groups and was unrelated to food or energy intake and energy expenditure. Serum insulin was higher in the LS than in the LC

  13. Serum Leptin and Adiponectin Levels in Breast Cancer Before and After Post Mastectomy Radiotherapy

    International Nuclear Information System (INIS)

    Nosseir, N.M.; Abdel -Messeih, Ph.L.; Mohamed, S.K.

    2010-01-01

    Obesity is a risk factor for postmenopausal breast cancer and is associated with poor prognosis. Leptin and adiponectin are cytokines synthesized in adipose tissue and have been implicated as a link between obesity and breast cancer. Therefore, in this study we analyzed and compared: serum leptin, adiponectin, lipid profile including cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) and body mass index (BMI) in breast cancer patients before and after Post Mastectomy Radio- therapy (PMRT).Serum leptin and adiponectin significantly increased and decreased respectively in patients after PMRT compared to the controls. BMI statistically decreased after radiotherapy while LDL-c increased in breast cancer patients; in both patients groups. HDL-c was statistically decreased but triglycerides showed significant increase in breast cancer patients. These results denoted that dyslipidemia may be associated with breast cancer risk and the evaluation of leptin and adiponectin can be used for follow up of patients under radiotherapy treatment for breast cancer

  14. Serum Leptin and Adiponectin Levels in Breast Cancer Before and After Post Mastectomy Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nosseir, N M; Abdel -Messeih, Ph L; Mohamed, S.K., E-mail: neveennosseir@Live.co [Health Radiation Research Department, National Center for Radiation Research and Technology, P.O.Box:29 Nasr City-Cairo (Egypt)

    2010-07-01

    Obesity is a risk factor for postmenopausal breast cancer and is associated with poor prognosis. Leptin and adiponectin are cytokines synthesized in adipose tissue and have been implicated as a link between obesity and breast cancer. Therefore, in this study we analyzed and compared: serum leptin, adiponectin, lipid profile including cholesterol, triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) and body mass index (BMI) in breast cancer patients before and after Post Mastectomy Radio- therapy (PMRT).Serum leptin and adiponectin significantly increased and decreased respectively in patients after PMRT compared to the controls. BMI statistically decreased after radiotherapy while LDL-c increased in breast cancer patients; in both patients groups. HDL-c was statistically decreased but triglycerides showed significant increase in breast cancer patients. These results denoted that dyslipidemia may be associated with breast cancer risk and the evaluation of leptin and adiponectin can be used for follow up of patients under radiotherapy treatment for breast cancer

  15. Three months of high-fructose feeding fails to induce excessive weight gain or leptin resistance in mice.

    Directory of Open Access Journals (Sweden)

    Erik J Tillman

    Full Text Available High-fructose diets have been implicated in obesity via impairment of leptin signaling in humans and rodents. We investigated whether fructose-induced leptin resistance in mice could be used to study the metabolic consequences of fructose consumption in humans, particularly in children and adolescents. Male C57Bl/6 mice were weaned to a randomly assigned diet: high fructose, high sucrose, high fat, or control (sugar-free, low-fat. Mice were maintained on their diets for at least 14 weeks. While fructose-fed mice regularly consumed more kcal and expended more energy, there was no difference in body weight compared to control by the end of the study. Additionally, after 14 weeks, both fructose-fed and control mice displayed similar leptin sensitivity. Fructose-feeding also did not change circulating glucose, triglycerides, or free fatty acids. Though fructose has been linked to obesity in several animal models, our data fail to support a role for fructose intake through food lasting 3 months in altering of body weight and leptin signaling in mice. The lack of impact of fructose in the food of growing mice on either body weight or leptin sensitivity over this time frame was surprising, and important information for researchers interested in fructose and body weight regulation.

  16. Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

    Science.gov (United States)

    Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

    2012-04-01

    The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

  17. Decreasing methane yield with increasing food intake keeps daily methane emissions constant in two foregut fermenting marsupials, the western grey kangaroo and red kangaroo.

    Science.gov (United States)

    Vendl, Catharina; Clauss, Marcus; Stewart, Mathew; Leggett, Keith; Hummel, Jürgen; Kreuzer, Michael; Munn, Adam

    2015-11-01

    Fundamental differences in methane (CH4) production between macropods (kangaroos) and ruminants have been suggested and linked to differences in the composition of the forestomach microbiome. Using six western grey kangaroos (Macropus fuliginosus) and four red kangaroos (Macropus rufus), we measured daily absolute CH4 production in vivo as well as CH4 yield (CH4 per unit of intake of dry matter, gross energy or digestible fibre) by open-circuit respirometry. Two food intake levels were tested using a chopped lucerne hay (alfalfa) diet. Body mass-specific absolute CH4 production resembled values previously reported in wallabies and non-ruminant herbivores such as horses, and did not differ with food intake level, although there was no concomitant proportionate decrease in fibre digestibility with higher food intake. In contrast, CH4 yield decreased with increasing intake, and was intermediate between values reported for ruminants and non-ruminant herbivores. These results correspond to those in ruminants and other non-ruminant species where increased intake (and hence a shorter digesta retention in the gut) leads to a lower CH4 yield. We hypothesize that rather than harbouring a fundamentally different microbiome in their foregut, the microbiome of macropods is in a particular metabolic state more tuned towards growth (i.e. biomass production) rather than CH4 production. This is due to the short digesta retention time in macropods and the known distinct 'digesta washing' in the gut of macropods, where fluids move faster than particles and hence most likely wash out microbes from the forestomach. Although our data suggest that kangaroos only produce about 27% of the body mass-specific volume of CH4 of ruminants, it remains to be modelled with species-specific growth rates and production conditions whether or not significantly lower CH4 amounts are emitted per kg of meat in kangaroo than in beef or mutton production. © 2015. Published by The Company of Biologists Ltd.

  18. 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.

  19. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  20. Time course metabolome of Roux-en-Y gastric bypass confirms correlation between leptin, body weight and the microbiome.

    Directory of Open Access Journals (Sweden)

    Loqmane Seridi

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery. We analyzed the metabolome in association to five hormones (Adiponectin, Insulin, Ghrelin, Leptin, and Resistin, four peptide hormones (GIP, Glucagon, GLP1, and PYY, and two cytokines (IL-6 and TNF. PCA showed samples cluster by surgery time and many microbially driven metabolites (indoles in particular correlated with the three months after the surgery. Network analysis of metabolites revealed a connection between carbohydrate (mannosamine and glucosamine and glyoxylate and confirms glyoxylate association to diabetes. Only leptin and IL-6 had a significant association with the measured metabolites. Leptin decreased immediately after RYGB (before significant weight loss, whereas IL-6 showed no consistent response to RYGB. Moreover, leptin associated with tryptophan in support of the possible role of leptin in the regulation of serotonin synthesis pathways in the gut. These results suggest a potential link between gastric leptin and microbial-derived metabolites in the context of obesity and diabetes.

  1. [The effect of a single moderate physical exertion on serum leptin levels in patients with essential hypertension (preliminary results)].

    Science.gov (United States)

    Zyśko, D; Gajek, J; Jołda-Mydłowska, B

    2000-08-01

    Leptin is a product of the ob gene and is secreted by the adipose tissue. It takes part in regulation of nervous, cardiovascular, endocrine system and renal functions. The aim of this study was to assess the influence of short term moderate exercise on serum leptin levels in patients with arterial hypertension. The study group consisted of 34 patients with essential hypertension: 15 women (48.9 +/- 12.1 years old) and 19 men (43.5 +/- 14.6 years old). There were 7 patients with stage I of hypertension, 17 patients with stage II of hypertension and 10 patients with stage III of hypertension. The blood samples were taken before and after the exercise test. Serum leptin levels were assessed by radioimmunoassay. Serum leptin levels were significantly higher in women then in men. The logarithm of serum leptin levels after the exercise was significantly lower than before (0.8 +/- 0.4 and 0.9 +/- 0.5 respectively). The moderate, short term exercise decreases serum leptin levels in the hypertensive patients.

  2. The correlation between leptin and highly sensitive C-reactive protein levels in obese children aged 9-15 years

    Directory of Open Access Journals (Sweden)

    Sarah M. Warouw

    2011-02-01

    Full Text Available Background Obesity is a low level and chronic inflammatory condition predominantly affecting white adipose tissue, where macrophage infiltration is found. Leptin is one of many molecules relating obesity to cardiovascular disease. Leptin can increase cytokine production in macrophages and monocytes, and increase oxidative stress on endothelial cells. Pro-inflammatory cytokines, in turn, may trigger the release of C-reactive protein. Objective To examine the correlation between leptin and hsCRP in obese children aged 9-15 years. Methods This cross-sectional study was done in Manado from May to December 2009, on elementary and junior high school children. Subjects were obese children aged 9-15 years, with nutritional status detennined by Body Mass Index and converted into z-score. Physical examination, blood pressure, and blood examinations for  fasting blood sugar (FBS, lipid profile, leptin, and hsCRP were perfonned. Data were analyzed with appropriate statistical methods. Results The mean leptin level in obese children was 34,009.2 pgiL (SD 18,224.79, higher than that of the control, 7,760.9 pgiL (SD 8,859.55 (P<0.0001. The mean hsCRP level in obese children was 3.6 mgiL (SD 3.60, higher than that of the control, 0.7 mgiL (SD 1.32 (<0.0001. There was a significant positive correlation between leptin and hsCRP levels in obese children (r 0.355; P<0.0001. Conclusions There is significant positive correlation between leptin and hsCRP levels in obese children aged 9-15 years. Increased leptin and hsCRP levels indicate a low degree of chronic inflammation. Thus, intervention is needed to decrease the body weight of obese children.

  3. Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

    NARCIS (Netherlands)

    Zeinoaldini, S.; Swarts, J.J.M.; Heijning, van de B.J.M.

    2006-01-01

    Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset

  4. 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

    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 duplica...

  5. Acute regulation of plasma leptin by isoprenaline in lean and obese fasted subjects.

    Science.gov (United States)

    Baynes, K C R; Nicholas, M D; Shojaee-Moradie, F; Umpleby, A M; Giannoulis, M G

    2006-07-01

    In human obesity, there is some evidence for impaired adrenergic sensitivity with respect to catecholamine-induced lipolysis. The beta-adrenoceptor agonist isoprenaline has been shown to suppress plasma leptin levels in lean humans in vivo. We hypothesized that a reduced adrenergic sensitivity in obese humans would result in impaired suppression of leptin secretion. Eight obese [Ob, body mass index (BMI) = 33.3 kg/m2] and seven lean (Ln, BMI = 21.8 kg/m2) men were studied after an overnight fast. Intravenous isoprenaline infusion was initiated at a rate of 8 ng/kg/min, titrated up to 24 ng/kg/min over 30 min and continued at this rate for a further 120 min with continuous electrocardiogram monitoring. Baseline fasting plasma leptin was higher in obese compared with lean subjects (Ob 12.2 +/- 1.8, Ln 2.6 +/- 0.6 ng/ml, p fasting glycerol as a measure of lipolysis was similar in both groups (Ob 62.9 +/- 7.6, Ln 42.4 +/- 8.9 micromol/l) and increased from baseline to 150 min by equivalent amounts (Ob +66.9%, Ln +81.2%, p = NS). Plasma leptin decreased from baseline to 150 min with similar relative changes in both groups (Ob -29.2%, Ln -27.8%). Obese subjects show a similar lipolytic and leptin response to acute isoprenaline infusion compared with lean subjects. Impaired beta-adrenergic-induced inhibition of leptin secretion does not appear to contribute to hyperleptinaemia in obese human subjects.

  6. Habitual dietary intake of fatty acids are associated with leptin gene expression in subcutaneous and visceral adipose tissue of patients without diabetes.

    Science.gov (United States)

    Rostami, Hosein; Samadi, Mohammad; Yuzbashian, Emad; Zarkesh, Maryam; Asghari, Golaleh; Hedayati, Mehdi; Daneshafrooz, Afsoon; Mirmiran, Parvin; Khalaj, Alireza

    2017-11-01

    The purpose of the study was to investigate the association of leptin gene expression in visceral and subcutaneous adipose tissues with habitual fatty acid intake and its subtypes in adults. Visceral and subcutaneous adipose tissues were gathered from 97 participants aged ≥ 20, who had undergone elective abdominal surgery. Dietary fatty acid intakes including total fatty acids (TFA), saturated fatty acid (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-3, n-6, and n-9 fatty acids were collected using a valid and reliable food-frequency questionnaire (FFQ). The leptin gene expression in visceral and subcutaneous adipose tissues was measured by Real-Time PCR. After controlling for body mass index (BMI) and insulin, energy-adjusted dietary intake of SFA was positively and MUFA and n-3 fatty acids were negatively associated with subcutaneous and visceral adipose tissues leptin gene expression. Besides, a significant negative association of PUFA, n-6, and n-9 fatty acids with leptin mRNA from visceral adipose tissue were observed. In order to better interpretations of the results, the participants were allocated two groups including non-obese (BMI fatty acids had a negative association with visceral leptin gene expression. Habitual intake of SFA, MUFA, and n-3 fatty acids were associated with leptin gene expression in visceral and subcutaneous adipose tissues, suggesting an important role of quality and quantity of fatty acids intake in adipose tissue to regulate leptin expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The cellular and molecular bases of leptin and ghrelin resistance in obesity.

    Science.gov (United States)

    Cui, Huxing; López, Miguel; Rahmouni, Kamal

    2017-06-01

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

  8. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin concentrations in older and young adults: evidence for increased CCK activity as a cause of the anorexia of aging.

    NARCIS (Netherlands)

    MacIntosh, C.G.; Morley, J.E.; Wishart, J.M.; Morris, H.A.; Jansen, J.B.M.J.; Horowitz, M.M.; Chapman, I.M.

    2001-01-01

    Healthy aging is associated with reductions in appetite and food intake--the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on

  9. HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

    Science.gov (United States)

    White, Christy L.; Whittington, Amy; Barnes, Maria J.; Wang, Zhong; Bray, George A.; Morrison, Christopher D.

    2009-01-01

    Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin sensitivity following 28 days of high-fat (HF) feeding in rats. A significant increase in PTP1B mRNA levels was also observed in rats chronically infused with leptin (3 μg/day icv) for 14 days (P = 0.01) and in leptin-deficient ob/ob mice infused with leptin (5 μg/day sc for 14 days; P = 0.003). When saline-infused ob/ob mice were placed on a HF diet for 14 days, an increase in hypothalamic PTP1B mRNA expression was detected (P = 0.001) despite the absence of circulating leptin. In addition, although ob/ob mice were much more sensitive to leptin on a low-fat (LF) diet, a reduction in this sensitivity was still observed following exposure to a HF diet. Taken together, these data indicate that hypothalamic PTP1B is specifically increased during HF diet-induced leptin resistance. This increase in PTP1B is due in part to chronic hyperleptinemia, suggesting that hyperleptinemia is one mechanism contributing to the development of leptin resistance. However, these data also indicate that leptin is not required for the increase in hypothalamic PTP1B or the development of leptin resistance. Therefore, additional, leptin-independent mechanisms must exist that increase hypothalamic PTP1B and contribute to leptin resistance. PMID:19017730

  10. Growth Hormone Overexpression Disrupts Reproductive Status Through Actions on Leptin

    Directory of Open Access Journals (Sweden)

    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

  11. 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)

  12. Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice.

    Science.gov (United States)

    Wei, Zhikui; Lei, Xia; Petersen, Pia S; Aja, Susan; Wong, G William

    2014-04-01

    Transgenic overexpression of CTRP9, a secreted hormone downregulated in obesity, confers striking protection against diet-induced obesity and type 2 diabetes. However, the physiological relevance of this adiponectin-related plasma protein remains undefined. Here, we used gene targeting to establish the metabolic function of CTRP9 in a physiological context. Mice lacking CTRP9 were obese and gained significantly more body weight when fed standard laboratory chow. Increased food intake, due in part to upregulated expression of hypothalamic orexigenic neuropeptides, contributed to greater adiposity in CTRP9 knockout mice. Although the frequency of food intake remained unchanged, CTRP9 knockout mice increased caloric intake by increasing meal size and decreasing satiety ratios. The absence of CTRP9 also resulted in peripheral tissue insulin resistance, leading to increased fasting insulin levels, impaired hepatic insulin signaling, and reduced insulin tolerance. Increased expression of lipogenic genes, combined with enhanced caloric intake, contributed to hepatic steatosis in CTRP9 knockout mice. Loss of CTRP9 also resulted in reduced skeletal muscle AMPK activation and mitochondrial content. Together, these results provide the genetic evidence for a physiological role of CTRP9 in controlling energy balance via central and peripheral mechanisms.

  13. 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.

  14. 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

  15. Ghrelin, leptin and insulin in cirrhotic children and adolescents: relationship with cirrhosis severity and nutritional status.

    Science.gov (United States)

    Dornelles, Cristina T L; Goldani, Helena A S; Wilasco, Maria Inês A; Maurer, Rafael L; Kieling, Carlos O; Porowski, Marilene; Ferreira, Cristina T; Santos, Jorge L; Vieira, Sandra M G; Silveira, Themis R

    2013-01-10

    Ghrelin, leptin, and insulin concentrations are involved in the control of food intake and they seem to be associated with anorexia-cachexia in cirrhotic patients. The present study aimed to investigate the relationship between the nutritional status and fasting ghrelin, leptin and insulin concentrations in pediatric cirrhotic patients. Thirty-nine patients with cirrhosis and 39 healthy controls aged 0-15 years matched by sex and age were enrolled. Severity of liver disease was assessed by Child-Pugh classification, and Pediatric for End Stage Liver Disease (PELD) or Model for End-stage Liver Disease (MELD) scores. Blood samples were collected from patients and controls to assay total ghrelin, acyl ghrelin, leptin and insulin by using a commercial ELISA kit. Anthropometry parameters used were standard deviation score of height-for-age and triceps skinfold thickness-for-age ratio. A multiple linear regression analysis was used to determine the correlation between dependent and independent variables. Acyl ghrelin was significantly lower in cirrhotic patients than in controls [142 (93-278) pg/mL vs 275 (208-481) pg/mL, P=0.001]. After multiple linear regression analysis, total ghrelin and acyl ghrelin showed an inverse correlation with age; acyl ghrelin was associated with the severity of cirrhosis and des-acyl ghrelin with PELD or MELD scores ≥15. Leptin was positively correlated with gender and anthropometric parameters. Insulin was not associated with any variable. Low acyl ghrelin and high des-acyl ghrelin concentrations were associated with cirrhosis severity, whereas low leptin concentration was associated with undernourishment in children and adolescents with cirrhosis. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model

    Directory of Open Access Journals (Sweden)

    Xiao Tan

    2017-02-01

    Full Text Available Persistent organic pollutants (POPs pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route, inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions (I-consistency and I I -consistency are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I-consistency results were more acceptable than the I I -consistency results.

  17. Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model.

    Science.gov (United States)

    Tan, Xiao; Gong, Zaiwu; Huang, Minji; Wang, Zhou-Jing

    2017-02-14

    Persistent organic pollutants (POPs) pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route), inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions ( I -consistency and I I -consistency) are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I -consistency results were more acceptable than the I I -consistency results.

  18. 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.

  19. Elevated hypothalamic TCPTP in obesity contributes to cellular leptin resistance

    Science.gov (United States)

    Loh, Kim; Fukushima, Atsushi; Zhang, Xinmei; Galic, Sandra; Briggs, Dana; Enriori, Pablo J.; Simonds, Stephanie; Wiede, Florian; Reichenbach, Alexander; Hauser, Christine; Sims, Natalie A.; Bence, Kendra K.; Zhang, Sheng; Zhang, Zhong-Yin; Kahn, Barbara B.; Neel, Benjamin G.; Andrews, Zane B.; Cowley, Michael A.; Tiganis, Tony

    2011-01-01

    SUMMARY In obesity, anorectic responses to leptin are diminished, giving rise to the concept of ‘leptin resistance’. Increased expression of protein tyrosine phosphatase 1B (PTP1B) has been associated with the attenuation of leptin signaling and development of cellular leptin resistance. Here we report that hypothalamic levels of the tyrosine phosphatase TCPTP are also elevated in obesity to attenuate the leptin response. We show that mice that lack TCPTP in neuronal cells have enhanced leptin sensitivity and are resistant to high fat diet-induced weight gain and the development of leptin resistance. Also, intracerebroventricular administration of a TCPTP inhibitor enhances leptin signaling and responses in mice. Moreover, the combined deletion of TCPTP and PTP1B in neuronal cells has additive effects in the prevention of diet-induced obesity. Our results identify TCPTP as a critical negative regulator of hypothalamic leptin signaling and causally link elevated TCPTP to the development of cellular leptin resistance in obesity. PMID:22000926

  20. Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

    Science.gov (United States)

    Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy; Awara, Mahmoud A; Moniz, Caje; le Roux, Carel W

    2011-09-01

    Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.

  1. Role of adiponectin and leptin on body development in infants during the first year of life

    Directory of Open Access Journals (Sweden)

    Gasparoni Antonella

    2010-03-01

    Full Text Available Abstract Background The control of growth and nutritional status in the foetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to evaluate levels of adiponectin, leptin and insulin in appropriate (AGA and small for gestational age (SGA children during the 1st year of life and to correlate these with auxological parameters. Methods In 33 AGA and 29 SGA infants, weight, length, head circumference, glucose, insulin, adiponectin and leptin levels were evaluated at the second day of life, and at one, six and twelve months, during which a portion of SGA could show catch-up growth (rapid growth in infants born small for their gestational age. Results Both total and isoform adiponectin levels were comparable between AGA and SGA infants at birth and until age one year. These levels significantly increased from birth to the first month of life and then decreased to lower values at 1 year of age in all subjects. Circulating leptin concentrations were higher in AGA (2.1 ± 4.1 ng/ml than in SGA neonates (0.88 ± 1.03 ng/ml, p st and the 6th month of age, but they increased in SGA from six months to one year, when they showed catch-up growth. Circulating insulin levels were not statistically different in AGA and SGA neonates at any study time point. Insulin levels in both AGA and SGA infants increased over the study period, and were significantly lower at birth compared to one, six and 12 months of age. Conclusions During the first year of life, in both AGA and SGA infants a progressive decrease in adiponectin levels was observed, while a difference in leptin values was correlated with the nutritional status.

  2. Leptin promotes wound healing in the oral mucosa.

    Science.gov (United States)

    Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

    2014-01-01

    Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

  3. 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.

  4. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High Fat Diets

    Directory of Open Access Journals (Sweden)

    Laurence B Lindenmaier

    2016-08-01

    Full Text Available Low bone mass is often associated with increased bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Genetic (e.g., leptin deficiency and high fat diet-induced (e.g., leptin resistance obesity are associated with increased marrow adipose tissue (MAT and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice using recombinant adeno-associated virus (rAAV gene therapy. In a first study, eight- to ten-week-old male ob/ob mice were randomized into 4 groups: (1 untreated, (2 rAAV-Lep, (3 rAAV-green fluorescent protein (rAAV-GFP, or (4 pair-fed to rAAV-Lep. For vector administration, mice were placed in a Kopf stereotaxic apparatus, and injected intracerebroventricularly with either rAAV-Lep or rAAV-GFP (9 × 107 particles in 1.5 µl. The mice were maintained for 30 weeks following vector administration. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high fat diets. Eight- to ten-week-old male ob/ob mice were randomized into 2 groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high fat diet for 8 weeks. Wild type (WT controls included age-matched mice fed regular or high fat diet. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high fat diet to values similar to WT mice fed regular diet. These

  5. Turmeric Supplementation Improves Serum Glucose Indices and Leptin Levels in Patients with Nonalcoholic Fatty Liver Diseases.

    Science.gov (United States)

    Navekar, Roya; Rafraf, Maryam; Ghaffari, Aida; Asghari-Jafarabadi, Mohammad; Khoshbaten, Manouchehr

    2017-01-01

    Insulin and leptin resistance are important risk factors for non-alcoholic fatty liver disease (NAFLD). There is limited evidence regarding the effects of turmeric on NAFLD. The aim of this study was to investigate the effects of turmeric supplementation on glycemic status and serum leptin levels in patients with NAFLD. This double-blind randomized controlled clinical trial was conducted on 46 patients with NAFLD (21males and 25 females) aged 20-60 years old and body mass index (BMI) between 24.9 and 40 kg/m2. The turmeric group (n = 23) was given six turmeric capsules daily for 12 weeks. Each capsule contained 500 mg turmeric powder (6×500 mg). The placebo group (n = 23) was given six placebo capsules daily for the same period. Fasting blood samples, anthropometric measurements, and physical activity levels were collected at the baseline and at the end of the study. Daily dietary intakes also were obtained throughout the study. Data were analyzed by independent t test, paired t test and analysis of covariance. Turmeric consumption decreased serum levels of glucose, insulin, HOMA-IR and leptin (by 1.22, 17.69, 19.48 and 21.33% respectively, p Turmeric supplementation improved glucose indexes and serum leptin levels and may be useful in the control of NAFLD complications.

  6. Helicobacter pylori infection and serum leptin, obestatin, and ghrelin levels in Mexican schoolchildren.

    Science.gov (United States)

    Romo-González, Carolina; Mendoza, Eugenia; Mera, Robertino M; Coria-Jiménez, Rafael; Chico-Aldama, Patricia; Gomez-Diaz, Rita; Duque, Ximena

    2017-10-01

    BackgroundThere is little information about the possible role of Helicobacter pylori infection on appetite-regulating peptides in children. This study evaluated the association between H. pylori infection and serum levels of ghrelin, leptin, and obestatin in schoolchildren.MethodsOne hundred seventy-eight schoolchildren, students at boarding schools in Mexico City, participated. H. pylori infection status was determined every 6 months for 1 year by a breath test using 13 C-urea; schoolchildren with consistently positive or negative results were selected to participate. Age, sex, and body mass index (BMI) were recorded. Serum concentrations of total ghrelin, leptin, and obestatin via specific enzyme-linked immunosorbent assays were determined.ResultsSchoolchildren with H. pylori infection had lower concentration of leptin, -0.54 pg/ml (95% CI: -0.98 to -0.09), compared to the schoolchildren without infection, after adjustment by age, gender, and BMI. And the children with the infection had a median of obestatin lower in 0.99 ng/ml (95% CI: -1.93 to -0.06) compared with the uninfected children after adjustment by BMI.ConclusionAssociation was found between H. pylori infection and decreased serum concentrations of leptin and obestatin. These results suggest that in schoolchildren, H. pylori infection affects the levels of hormones implicated in regulating appetite and energy homeostasis.

  7. Perception of academic examination stress: effects on serum leptin, cortisol, appetite and performance.

    Science.gov (United States)

    Inam, Qurrat-ul-Aen; Shireen, Erum; Haider, Saida; Haleem, Darakhshan Jabeen

    2011-01-01

    Examination stress is a psychological stress that activate hypothalamic-pituitary adrenocortical (HPA) axis to increase circulating levels of glucocorticoids. The fat derived hormone leptin is also released in response to stress-inducing condition. To workout the role of leptin and cortisol in response to perceived levels of examination stress and their effects on academic performance. The present study was designed to monitor the relationship of self reported perceived levels of examination stress on serum levels of cortisol and leptin in female students going to appear in university examination. Fifty-six female undergraduate students participated in the study. Examination stress, appetite levels were assessed by a questionnaire and blood samples were collected one hour before appearing in the examination. Performance was evaluated from the marks obtained in that particular examination. Serum cortisol levels increased with an increase in the intensity of perceived examination stress. Serum leptin levels increased only in the group under moderate stress while increases in mild and severe stress group were not significant. Mild to moderate stress enhanced performance but severe stress decreased it. The present study shows an inverted U-shaped relationship between self reported different levels of perceived examination stress and academic performance.

  8. The effect of obesity on inflammatory cytokine and leptin production following acute mental stress.

    Science.gov (United States)

    Caslin, H L; Franco, R L; Crabb, E B; Huang, C J; Bowen, M K; Acevedo, E O

    2016-02-01

    Obesity may contribute to cardiovascular disease (CVD) risk by eliciting chronic systemic inflammation and impairing the immune response to additional stressors. There has been little assessment of the effect of obesity on psychological stress, an independent risk factor for CVD. Therefore, it was of interest to examine interleukin-6, tumor necrosis factor-α, interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1Ra), and leptin following an acute mental stress task in nonobese and obese males. Twenty college-aged males (21.3 ± 0.56 years) volunteered to participate in a 20-min Stroop color-word and mirror-tracing task. Subjects were recruited for obese (body mass index: BMI > 30) and nonobese (BMI stress task elicited an increase in heart rate, catecholamines, and IL-1β in all subjects. Additionally, acute mental stress increased cortisol concentrations in the nonobese group. There was a significant reduction in leptin in obese subjects 30 min posttask compared with a decrease in nonobese subjects 120 min posttask. Interestingly, the relationship between the percent change in leptin and IL-1Ra at 120 min posttask in response to an acute mental stress task was only observed in nonobese individuals. This is the first study to suggest that adiposity in males may impact leptin and inflammatory signaling mechanisms following acute mental stress. © 2015 Society for Psychophysiological Research.

  9. A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

    Science.gov (United States)

    Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

    2017-08-01

    Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

  10. Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons.

    Science.gov (United States)

    Lee, Dong Kun; Jeong, Jae Hoon; Chun, Sung-Kun; Chua, Streamson; Jo, Young-Hwan

    2015-03-26

    Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin's action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signalling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signalling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons.

  11. Upregulation of miR21 and repression of Grhl3 by leptin mediates sinusoidal endothelial injury in experimental nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Sahar Pourhoseini

    Full Text Available Sinusoidal endothelial dysfunction (SED has been found to be an early event in nonalcoholic steatohepatitis (NASH progression but the molecular mechanisms underlying its causation remains elusive. We hypothesized that adipokine leptin worsens sinusoidal injury by decreasing functionally active nitric oxide synthase 3 (NOS3 via miR21. Using rodent models of NASH, and transgenic mice lacking leptin and leptin receptor, results showed that hyperleptinemia caused a 4-5 fold upregulation of hepatic miR21 as assessed by qRTPCR. The upregulation of miR21 led to a time-dependent repression of its target protein Grhl3 levels as shown by western blot analyses. NOS3-p/NOS3 ratio which is controlled by Grhl3 was significantly decreased in NASH models. SED markers ICAM-1, VEGFR-2, and E-selectin as assessed by immunofluorescence microscopy were significantly up regulated in the progressive phases of NASH. Lack of leptin or its receptor in vivo, reversed the upregulation of miR21 and restored the levels of Grhl3 and NOS3-p/NOS3 ratio coupled with decreased SED dysfunction markers. Interestingly, leptin supplementation in mice lacking leptin, significantly enhanced miR21 levels, decreased Grhl3 repression and NOS3 phosphorylation. Leptin supplementation in isolated primary endothelial cells, Kupffer cells and stellate cells showed increased mir21 expression in stellate cells while sinusoidal injury was significantly higher in all cell types. Finally miR21 KO mice showed increased NOS3-p/NOS3 ratio and reversed SED markers in the rodent models of NASH. The experimental results described here show a close association of leptin-induced miR21 in aiding sinusoidal injury in NASH.

  12. A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats.

    Directory of Open Access Journals (Sweden)

    Pascaline Aimé

    Full Text Available Insulin is involved in multiple regulatory mechanisms, including body weight and food intake, and plays a critical role in metabolic disorders such as obesity and diabetes. An increasing body of evidence indicates that insulin is also involved in the modulation of olfactory function. The olfactory bulb (OB contains the highest level of insulin and insulin receptors (IRs in the brain. However, a role for insulin in odor detection and sniffing behavior remains to be elucidated. Using a behavioral paradigm based on conditioned olfactory aversion (COA to isoamyl-acetate odor, we demonstrated that an intracerebroventricular (ICV injection of 14 mU insulin acutely decreased olfactory detection of fasted rats to the level observed in satiated animals. In addition, whereas fasted animals demonstrated an increase in respiratory frequency upon food odor detection, this effect was absent in fasted animals receiving a 14 mU insulin ICV injection as well as in satiated animals. In parallel, we showed that the OB and plasma insulin levels were increased in satiated rats compared to fasted rats, and that a 14 mU insulin ICV injection elevated the OB insulin level of fasted rats to that of satiated rats. We further quantified insulin receptors (IRs distribution and showed that IRs are preferentially expressed in the caudal and lateral parts of the main OB, with the highest labeling found in the mitral cells, the main OB projection neurons. Together, these data suggest that insulin acts on the OB network to modulate olfactory processing and demonstrate that olfactory function is under the control of signals involved in energy homeostasis regulation and feeding behaviors.

  13. Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice.

    Science.gov (United States)

    Bo, E; Farinetti, A; Marraudino, M; Sterchele, D; Eva, C; Gotti, S; Panzica, G

    2016-07-01

    Tributyltin (TBT), a pesticide used in antifouling paints, is toxic for aquatic invertebrates. In vertebrates, TBT may act in obesogen- inducing adipogenetic gene transcription for adipocyte differentiation. In a previous study, we demonstrated that acute administration of TBT induces c-fos expression in the arcuate nucleus. Therefore, in this study, we tested the hypothesis that adult exposure to TBT may alter a part of the nervous pathways controlling animal food intake. In particular, we investigated the expression of neuropeptide Y (NPY) immunoreactivity. This neuropeptide forms neural circuits dedicated to food assumption and its action is mediated by Y1 receptors that are widely expressed in the hypothalamic nuclei responsible for the regulation of food intake and energy homeostasis. To this purpose, TBT was orally administered at a dose of 0.025 mg/kg/day/body weight to adult animals [male and female C57BL/6 (Y1-LacZ transgenic mice] for 4 weeks. No differences were found in body weight and fat deposition, but we observed a significant increase in feed efficiency in TBT-treated male mice and a significant decrease in circulating leptin in both sexes. Computerized quantitative analysis of NPY immunoreactivity and Y1-related β-galactosidase activity demonstrated a statistically significant reduction in NPY and Y1 transgene expression in the hypothalamic circuit controlling food intake of treated male mice in comparison with controls. In conclusion, the present results indicate that adult exposure to TBT is profoundly interfering with the nervous circuits involved in the stimulation of food intake. © 2016 American Society of Andrology and European Academy of Andrology.

  14. Leptin level correlates with obesity and health related quality of life in obstructive sleep apnea syndrome patients.

    Science.gov (United States)

    Dubey, Abhishek; Kant, Surya; Tiwari, Sunita; Agarwal, Sarita; Mahdi, Abbas Ali

    2015-04-01

    Leptin takes part in regulation of energy balance, neuronal functions, pain and mood. It may act as intermediary marker for various components of HRQOL in patients of obstructive sleep apnea syndrome. To document the correlation among leptin levels, obesity and HRQoL in OSAS patients. A tertiary care hospital based cross-sectional study was done in 224 subjects aged 18-65 years, after taking informed consent. Subjects with previous history of smoking, Liver disease, COPD, CHD, T2 DM, asthma, cancer, end stage renal disease, heart failure, any endocrine disorder including Cushing syndrome, thyroid, on systemic steroid or any continuous medication for last 6 months, on dieting or suffering from any disability condition (other than obesity and OSAS) affecting their HRQoL were excluded from the study. All subjects underwent Polysomnography. Leptin assay was done by ELISA method. Hindi version of HRQoL tool SF-36 was used to evaluate HRQoL. SPSS 20 was used to analyse data. Three groups (AHI 15) were compared. Significant differences were observed in BMI, NC, WC, WHR and ESS. Differences were not significant in sleep architecture and Leptin level. SF-36 HRQoL, scores were observed decreased with increase in severity of disease. Leptin level was found significantly correlated with "Role limitations due to physical health problems", "Social functioning", Hypopnea and obesity indices. In these subjects Obesity indices are the most important correlates of Leptin level. Oxygen desaturation indices with exception of Hypopnea and HRQoL may not be exclusively correlated to leptin levels. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

  15. Menstrual cycle hormones, food intake, and cravings

    Science.gov (United States)

    Objective: Food craving and intake are affected by steroid hormones during the menstrual cycle, especially in the luteal phase, when craving for certain foods has been reported to increase. However, satiety hormones such as leptin have also been shown to affect taste sensitivity, and therefore food ...

  16. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension.

    Science.gov (United States)

    Bruder-Nascimento, Thiago; Butler, Benjamin R; Herren, David J; Brands, Michael W; Bence, Kendra K; Belin de Chantemèle, Eric J

    2015-12-01

    Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. 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.

  18. 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)

  19. Food restriction-induced changes in gonadotropin-inhibiting hormone-immunoreactive cells are associated with sexual motivation and food hoarding, but not sexual performance and food intake

    Directory of Open Access Journals (Sweden)

    Candice M Klingerman

    2011-12-01

    Full Text Available We hypothesized that putative anorectic and orexigenic peptides control the motivation to engage in either ingestive or sex behaviors, and these peptides function to optimize reproductive success in environments where energy fluctuates. Here, the putative orexigenic peptide, gonadotropin-inhibiting hormone (GnIH, also known as RFamide-related peptide-3 and the putative anorectic hormones leptin, insulin and estradiol were examined during the course of food restriction. Groups of female Syrian hamsters were restricted to 75% of their ad libitum food intake or fed ad libitum for 4, 8, or 12 days. Two other groups were food restricted for 12 days and then re-fed ad libitum for 4 or 8 days. After testing for sex and ingestive behavior, blood was sampled and assayed for peripheral hormones. Brains were immunohistochemically double-labeled for GnIH and the protein product of the immediate early gene, c-fos, a marker of cellular activation. Food hoarding, the number of double-labeled cells, and the percent of GnIH-Ir cells labeled with Fos-Ir were significantly increased at 8 and 12 days after the start of food restriction. Vaginal scent marking and GnIH-Ir cell number significantly decreased after the same duration of restriction. Food hoarding, but not food intake, was significantly positively correlated with cellular activation in GnIH-Ir cells. Vaginal scent marking was significantly negatively correlated with cellular activation in GnIH-Ir cells. There were no significant effects of food restriction on plasma insulin, leptin, estradiol, or progesterone concentrations. In the dorsomedial hypothalamus (DMH of energetically-challenged females, strong projections from NPY-Ir cells were found in close apposition to GnIH-Ir cells. Together these results are consistent with the idea that metabolic signals influence sexual and ingestive motivation via NPY fibers that project to GnIH cells in the DMH.

  20. Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction.

    Science.gov (United States)

    Chu, Alison; Thamotharan, Shanthie; Ganguly, Amit; Wadehra, Madhuri; Pellegrini, Matteo; Devaskar, Sherin U

    2016-10-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long-term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER] stress) that are immunologically mediated and important for cellular survival and functioning, and (3) the resulting IUGR phenotype and placental histopathology in this animal model. After subjecting pregnant mice to mild and moderate FR from gestational day 10 to 19, we collected placentas and embryos at gestational day 19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity. In summary, maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. 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.

  2. Interaction between serum leptin levels and hypothalamo-hypophyseal-thyroid axis in patients with anorexia nervosa.

    Science.gov (United States)

    Nedvídková, J; Papezová, H; Haluzík, M; Schreiber, V

    2000-05-01

    The main objective of the study was to evaluate the endocrinological picture of anorexia. Serum leptin levels are low in untreated anorexia nervosa (AN), but studies of the exact relationship between leptin, body weight and hormones of hypothalamo-hypophyseal-thyroid axis and the impact of refeeding in anorectics are limited. The sample consistent of 15 patients with anorexia nervosa before and 1 month after partial weight recovery, and 15 age-matched control subjects. The body mass index (BMI), leptin, plasma neuropeptide Y (NPY), serotonin, thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in serum were evaluated for each subject. The mean serum levels of leptin, T4, and T3 were significantly lower before weight recovery in 15 patients with AN than they were in control subjects. After partial weight recovery, basal T3 levels were unchanged and significantly lower than in controls. Basal T4 was even still more reduced, but we observed significantly elevated ratio of T3/T4 and reduced ratio rT3/T4 of in AN patients after gain recovery, indicating increased conversion of T4 to T3 than to rT3. The levels of serum leptin were low in AN, but after partial weight recovery slightly increased, and correlated with BMI. No differences were observed in serum NPY. Serum levels of IGF-1 and serotonin were lower in AN than in controls before and after partial weight gain. IGF-1 was slightly increased after partial weight gain. We did not find correlation between serum levels of leptin and serum T4. The low serum levels of T3 associated with chronic starvation were thought to be the result of impaired peripheral conversion of T4 to T3. However, decreased levels of T3 were still apparent even after a partial weight gain, and the concentration of T4 was even lower. The diminished serum level of TSH in AN, however, appeared to return to the level of controls. On the basis of these results, we assume that low serum levels of thyroid hormones in AN reflect a

  3. The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women.

    Science.gov (United States)

    Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

    2014-01-01

    Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were measured five times on 0, 7th, 14th and 28th days of Ramadan and on the 14th day post-Ramadan. The data were analyzed by SPSS software (version 11.5) using repeated measures ANOVA to find whether any changes occurred in the variables of interest during the study, and Pearson correlation coefficient was used to examine the relations among the variables. A significant change in fasting blood sugar, neuropeptide Y and leptin was observed during the study (pRamadan and increased after Ramadan, with the lowest value at the end of Ramadan. Neuropeptide Y increased both during Ramadan and two weeks after Ramadan. Also, leptin decreased significantly two weeks after Ramadan compared to the end of Ramadan. No significant change was observed in insulin level during the study (p>0.05). The result of this study revealed the important role of leptin and neuropeptide Y in the long term regulation of energy balance in pregnant women with chronic diurnal fasting, and it further revealed that Ramadan fasting did not significantly change the serum insulin level.

  4. Downregulation of leptin and resistin expression in blood following bariatric surgery.

    Science.gov (United States)

    Edwards, Claire; Hindle, A Katharine; Fu, Sidney; Brody, Fredrick

    2011-06-01

    Type 2 diabetes (T2D) resolves rapidly after bariatric surgery, even before substantial weight is lost. However, the molecular pathways underlying this phenomenon remain unclear. Microarray data has shown that numerous genes are differentially expressed in blood after bariatric surgery, including resistin and leptin. Resistin and leptin are circulating hormones derived from adipose tissue, which are associated with obesity and insulin resistance. This study examined expression of these genes before and after bariatric surgery in diabetic and nondiabetic obese patients. The study included 16 obese patients who underwent bariatric surgery, either Roux-en-Y gastric bypass (RYGB) or adjustable gastric banding. Eight patients had T2D. Preoperative blood samples were collected in PAXgene tubes to stabilize mRNA. Postoperative samples were collected 3 months after surgery. Total RNA was isolated and cDNA was synthesized. Real-time quantitative PCR was used to quantify mRNA. Results were analyzed using Student's t test with a P<0.05 considered significant. Postoperatively, five diabetic patients had discontinued hypoglycemic medications and one showed improved glycemic control. Both leptin and resistin mRNA levels were elevated in the diabetic group but decreased after surgery to levels near those of the nondiabetic group. Greater downregulation of resistin and leptin expression occurred in patients who lost more excess body weight (EBW), while patients who lost less than 10% EBW had a mean increase in expression of the two genes. Downregulation of both genes was more pronounced after RYGB compared to gastric banding. Downregulation of resistin and leptin gene expression after bariatric surgery may play a role in normalizing obesity-associated insulin resistance. Interestingly, downregulation is greater after RYGB and in patients who lose a greater proportion of EBW. Targeted therapies for obesity and diabetes may be developed by understanding the pathways by which these

  5. Osteocalcin as a negative regulator of serum leptin concentration in humans: insight from triathlon competitions.

    Science.gov (United States)

    Guadalupe-Grau, Amelia; Ara, Ignacio; Dorado, Cecilia; Vicente-Rodríguez, German; Perez-Gomez, Jorge; Cabrero, Javier Chavarren; Serrano-Sanchez, José A; Santana, Alfredo; Calbet, Jose A L

    2010-10-01

    Osteocalcin is a hormone produced by osteoblasts which acts as a negative regulator of fat mass, protecting against diet induced obesity and insulin resistance in rodents. To determine if an acute increase in osteocalcin concentration is associated with opposed changes in circulating leptin levels and insulin resistance we studied 15 middle and long distance male triathletes, (age 32.1 ± 6.9 years), before and 48 h after an Olympic (OT) or an Ironman (IT) triathlon competition. Muscle power, anaerobic capacity, body composition (dual-energy X-ray absorptiometry), and serum concentrations of testosterone, dihydrotestosterone, osteocalcin, leptin, glucose, insulin and insulin resistance (HOMA) were determined pre- and post-race. Pre- and 48 h post-race total and regional lean body mass was not altered, but fat mass was similarly increased (~250 g) 48 h after the competitions. This elicited an increase in plasma leptin of 33% after the IT while it remained unchanged after the OT, likely due to a 25% increase in plasma osteocalcin which occurred only after the OT (all p < 0.05). Post-race HOMA remained unchanged in OT and IT. Performance was normalized 48 h after the competitions, with the exception of a slightly lower jumping capacity after the IT. Serum testosterone concentration tended to decrease by 10% after the IT whilst dihydrotestosterone was reduced by 24% after the IT. In conclusion, an acute increase in serum osteocalcin concentration blunts the expected increase of serum leptin concentration that should occur with fat mass gain. This study provides evidence for osteocalcin as a negative regulator of serum leptin in humans.

  6. 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.

  7. [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.

  8. Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.

    Science.gov (United States)

    Delgado, María Gabriela; Gracia-Sancho, Jordi; Marrone, Giusi; Rodríguez-Vilarrupla, Aina; Deulofeu, Ramon; Abraldes, Juan G; Bosch, Jaume; García-Pagán, Juan Carlos

    2013-10-01

    Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction, and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 wk. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavailability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis, were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability and with decreased O2(-) levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. In conclusion, the present study shows that blockade of the leptin signaling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.

  9. Relationship between serum leptin levels, ATPase activity of erythrocyte membrance and development of diabetic nephropathy in patients with DM2

    International Nuclear Information System (INIS)

    Wang Yuming

    2009-01-01

    Objective: To study the possible mechanism of development of nephrosis affected by changes of serum leptin levels and alteration of activities of Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase of erythrocyte membrane in patients with type 2 diabetes(DM2). Methods: Serum leptin levels (with RIA) and erythrocyte membrane Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase activitities (with Reinila method) were determined in 40 DM2 patients without nephropathy, 32 DM2 patients with nephropathy and 35 controls. Results Serum leptin levels were significantly higher in the diabetics as a whole than those in controls (P + K + -ATPase and Ca 2+ Mg 2+ -ATPase activities were significantly lower (P<0.01). Among the diabetic patients, the serum leptin levels in patients without nephrosis (P<0.05), but the RBC membrance ATPase activities were significantly lower(P<0.05). Conclusion: Development of type 2 diabetes nephrosis might be correlated with the high serum leptin level and decreased ATPase activities of erythrocite membrane. (authors)

  10. Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit

    Directory of Open Access Journals (Sweden)

    Heiko Löhr

    2018-05-01

    Full Text Available Summary: Anorexigenic pro-opiomelanocortin (Pomc/alpha-melanocyte stimulating hormone (αMSH neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca. In turn, this leads to reduced activation of hypophysiotropic somatostatin (Sst-neurons that express the melanocortin receptor Mc4r, elevated growth hormone (GH expression in the pituitary, and enhanced somatic growth. Mc4r expression and αMSH responsiveness are conserved in Sst-expressing hypothalamic neurons of mice. Thus, acquired leptin resistance and attenuation of pomca transcription in response to excessive caloric intake may represent an ancient mechanism to promote somatic growth when food resources are plentiful. : The melanocortin system controls energy homeostasis and somatic growth, but the underlying mechanisms are elusive. Löhr et al. identify a functional neural circuit in which Pomc neurons stimulate hypothalamic somatostatin neurons, thereby inhibiting hypophyseal growth hormone production. Excessive feeding and acquired leptin resistance attenuate this pathway, allowing faster somatic growth when food resources are rich. Keywords: Pomc neuron, somatostatin neuron, somatic growth, growth hormone, melanocortin system, high-fat diet, obesity, leptin resistance, zebrafish, mouse

  11. 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 insulin (p insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.

  12. The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system.

    Science.gov (United States)

    Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik; Hallén, Anna; Bäckhed, Fredrik; Jansson, John-Olov

    2013-10-01

    The gut microbiota contributes to fat mass and the susceptibility to obesity. However, the underlying mechanisms are not completely understood. To investigate whether the gut microbiota affects hypothalamic and brainstem body fat-regulating circuits, we compared gene expression of food intake-regulating neuropeptides between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R mice had decreased expression of the antiobesity neuropeptide glucagon-like peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both the hypothalamus and the brainstem, CONV-R mice had decreased expression of the antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and agouti-related protein (Agrp), and increased expression of the antiobesity peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated transcript (Cart) in the hypothalamus. The latter changes in neuropeptide expression could be secondary to elevated fat mass in CONV-R mice. Leptin treatment caused less weight reduction and less suppression of orexigenic Npy and Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic expression of leptin resistance-associated suppressor of cytokine signaling 3 (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and Bdnf, an alteration that may contribute to fat mass induction by the gut microbiota. Moreover, the presence of body fat-inducing gut microbiota is associated with hypothalamic signs of Socs-3-mediated leptin resistance, which may be linked to failed compensatory body fat reduction.

  13. Impaired leptin gene expression and release in cultured preadipocytes isolated from individuals born with low birth weight

    DEFF Research Database (Denmark)

    Schultz, Ninna S; Broholm, Christa; Gillberg, Linn

    2014-01-01

    controls born with normal birth weight (NBW). Biopsies were obtained from subcutaneous abdominal fat depots and preadipocytes were isolated and cultured. Gene expression of leptin and selected differentiation markers were analyzed during preadipocyte differentiation and cell culture media was collected......Low birth weight (LBW) is associated with increased risk of developing type 2 diabetes (T2D). The appetite-regulating hormone leptin is released from mature adipocytes and its production may be decreased in immature preadipocytes from LBW individuals. We recruited 14 men born with LBW and 13...

  14. Leptin: A Link Between Energy Imbalance and Exercise-Induced Amenorrhea in Female Athletes

    OpenAIRE

    Miles, Marie

    2001-01-01

    Up to a quarter of female athletes may experience exercise-induced amenorrhea, depending on the type of sport and the level of competition. This amenorrhea is a component of the Female Athlete Triad, a term used to describe three interrelated conditions commonly seen together in the elite female athlete: chronic dieting and/or disordered eating, amenorrhea, and decreased bone mass. Leptin, a hormone secreted by adipose tissue and believed to play a central role in eating behaviors and energy ...

  15. Effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13 and IL-2 in bronchial asthmatic children

    International Nuclear Information System (INIS)

    Pan Jiongwei

    2011-01-01

    Objective: To determine the effect of long-term inhalation of glucocorticoids on the level of leptin, IL-13, and IL-2 in bronchial asthmatic patient. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum IL-13 and IL-2 level in 60 healthy persons (normal control group) and 70 bronchial asthma patients untreated and 3, 6, 12 months post-treatment, meanwhile leptin was determined by radio immunoassay. Results: The serum levels of leptin, Il-13, and IL-2 in were significantly increased in patient with bronchial asthma compared with that in the normal control group. The serum levels of leptin, IL-13, and IL-2 in children with asthma were decreased gradually after inhaling glucocorticoids for 3 months (P<0.05). The treatment of inhaled glucocorticoids for 6 and 12 months can attenuate the elevation of leptin, IL-13, and IL-2 compared with that before the treatment. Conclusion: Long-term inhaled glucocorticoid is an important means for asthma, and the effects are related to the decrease of level of leptin, IL-13, and IL-2. (authors)

  16. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  17. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  18. [Plasma levels of insulin and leptin in patients with morbid obesity and anorexia nervosa after weight loss or gain, respectively].

    Science.gov (United States)

    Escobar, L; Freire, J M; Girón, J A; Vázquez, J M; Pajares, M; Ortego, J; Gavilán, I; Chover, A J; Carrasco, M; Epinosa, R; Marín, F; Aguilar, M

    2000-06-01

    The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese

  19. Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications.

    Science.gov (United States)

    Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P

    2002-05-01

    Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients

  20. 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.

  1. 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.

  2. Decreases in High-Fat and/or High-Added-Sugar Food Group Intake Occur when a Hypocaloric, Low-Fat Diet Is Prescribed Within a Lifestyle Intervention: A Secondary Cohort Analysis.

    Science.gov (United States)

    Sheikh, Vaishali Keshani; Raynor, Hollie A

    2016-10-01

    When a hypocaloric, low-fat diet is prescribed, intake of currently consumed foods can decrease, foods naturally low in fat and/or added sugar may increase, or fat- or sugar-modified foods may increase. To examine food group intake change and its relation to reductions in energy and fat intake and weight during a lifestyle intervention. Secondary cohort analysis. One hundred sixty-nine participants (aged 52.0±8.6 years, body mass index 34.9±4.5, 92% white, 97.6% non-Hispanic, and 56.8% women) with complete data at 0 and 6 months collected in a research setting. From three 24-hour telephone dietary recalls, 165 food groups from Nutrition Data System for Research software were coded into 25 larger food groups assessing intake of higher-fat and/or added-sugar food groups vs naturally lower-fat and/or added-sugar food groups and into 17 larger food groups assessing intake of nonmodified vs fat- and/or sugar-modified food groups. Repeated measures analyses of covariance (intervention group: covariate) assessed changes from 0 to 6 months. Hierarchical regressions examined changes in food group intake and changes in energy intake, percent energy from fat intake, and w