scholarly journals Suppression of Leptin Receptor Messenger Ribonucleic Acid and Leptin Responsiveness in the Ventromedial Nucleus of the Hypothalamus during Pregnancy in the Rat

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3868-3874 ◽  
Author(s):  
S. R. Ladyman ◽  
D. R. Grattan
Keyword(s):  
Choroid Plexus ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Ventromedial Nucleus ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Messenger Ribonucleic Acid ◽  
Leptin Receptors ◽  
Receptor Isoforms

Abstract Pregnancy in the rat is a state of leptin resistance associated with impaired leptin signal transduction in the hypothalamus. The aim of this study was to determine whether this leptin-resistant state is mediated by a change in the level of leptin receptors in the hypothalamus. Real-time RT-PCR was used to determine levels of mRNA for the various leptin receptor isoforms in a number of microdissected hypothalamic nuclei and the choroid plexus. To investigate the functional activation of the leptin receptor, immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (pSTAT3) was examined in the arcuate nucleus and the ventromedial nucleus of the hypothalamus (VMH) of fasted diestrous and d-14 pregnant rats after an intracerebroventricular (i.c.v.) injection of either leptin (4 μg) or vehicle. A significant reduction of Ob-Rb mRNA levels was observed in the VMH during pregnancy compared with the nonpregnant controls. Furthermore, in pregnant rats the number of cells positive for leptin-induced pSTAT3 in the VMH was greatly reduced during pregnancy compared with nonpregnant rats. There were no differences in the level of Ob-Rb mRNA or in the number of leptin-induced pSTAT3-positive cells in the arcuate nucleus of nonpregnant and pregnant rats. These data implicate the VMH as a key hypothalamic site involved in pregnancy-induced leptin resistance. There were also reduced levels of mRNA for Ob-Ra, a proposed leptin transporter molecule, in the choroid plexus on d 7 and 21 of pregnancy. Hence, diminished transport of leptin into the brain may also contribute to pregnancy-induced leptin resistance.

scholarly journals Seasonal and Nutritional Fluctuations in the mRNA Levels of the Short Form of the Leptin Receptor (LRa) in the Hypothalamus and Anterior Pituitary in Resistin-Treated Sheep

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2451
Author(s):  
Weronika Biernat ◽  
Malgorzata Szczęsna ◽  
Katarzyna Kirsz ◽  
Dorota Anna Zieba
Keyword(s):  
Anterior Pituitary ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Preoptic Area ◽  
Short Form ◽  
Leptin Resistance ◽  
Mrna Levels ◽  
Mrna Transcript ◽  
The Central Nervous System ◽  
Short Days

The short form of the leptin receptor (LRa) plays a key role in the transport of leptin to the central nervous system (CNS). Here, the resistin (RSTN)-mediated expression of LRa in the preoptic area (POA), ventromedial and dorsomedial nuclei (VMH/DMH),arcuate nucleus (ARC) and the anterior pituitary gland (AP)was analyzed considering the photoperiodic (experiment 1) and nutritional status (experiment 2) of ewes. In experiment 1, 30 sheep were fed normally and received one injection of saline or two doses of RSTN one hour prior to euthanasia. RSTN increased LRa expression mainly in the ARC and AP during long days (LD) and only in the AP during short days (SD). In experiment 2, an altered diet for 5 months created lean or fat sheep. Twenty sheep were divided into four groups: the lean and fat groups were given saline, while the lean-R and fat-R groups received RSTN one hour prior to euthanasia. Changes in adiposity influenced the effect of RSTN on LRa mRNA transcript levels in the POA, ARC and AP and without detection of LRa in the VMH/DMH. Overall, both photoperiodic and nutritional signals influence the effects of RSTN on leptin transport to the CNS and are involved in the adaptive/pathological phenomenon of leptin resistance in sheep.

scholarly journals Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3704-3711 ◽  
Author(s):  
S. R. Ladyman ◽  
D. R. Grattan
Keyword(s):  
Food Intake ◽  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
Pregnant Rats ◽  
Hypothalamic Nuclei ◽  
Stat3 Phosphorylation ◽  
Vehicle Treatment ◽  
Plasma Leptin

Abstract Leptin concentrations increase during pregnancy, but this does not prevent the pregnancy-induced increase in food intake, suggesting a state of leptin resistance. This study investigated the response to intracerebroventricular leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14 pregnant rats received leptin (4 μg) or vehicle, then food intake was measured. Serial blood samples were collected in another group of rats to determine plasma leptin concentrations. Further groups of d-14 pregnant and nonpregnant rats were killed after leptin or vehicle treatment, and brains were collected. Hypothalamic nuclei were microdissected, and levels of signal transducer and activator of transcription (STAT)3 phosphorylation were measured using Western blot analysis. Fasting decreased leptin concentrations in both pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition, there was no postfasting hyperphagic response in the pregnant rats. In the pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and lateral hypothalamus was not different between pregnant and nonpregnant rats. These data indicate that pregnant rats become resistant to the satiety action of leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during pregnancy, specifically in the arcuate nucleus and VMH. These data support the hypothesis that pregnancy is a state of hypothalamic leptin resistance.

scholarly journals Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade

2020 ◽  
Author(s):  
Chen Li ◽  
Fantao Meng ◽  
Yun Lei ◽  
Jing Liu ◽  
Jing Liu ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Leptin Receptor ◽  
Histone Acetyltransferase ◽  
Expression Profiles ◽  
Mrna Levels ◽  
Bdnf Gene ◽  
Leptin Receptors ◽  
Pleiotropic Functions ◽  
H3 Acetylation ◽  
Stimulation Of

Abstract Leptin is an adipocyte-derived hormone with pleiotropic functions affecting appetite and mood. While leptin’s role in the regulation of appetite has been extensively studied in hypothalamic neurons, its function in the hippocampus, where it regulates mood-related behaviors, is poorly understood. Here, we show that the leptin receptor (LepRb) colocalizes with brain-derived neurotrophic factor (BDNF), a key player in the pathophysiology of major depression and the action of antidepressants, in the dentate gyrus of the hippocampus. Leptin treatment increases, whereas deficiency of leptin or leptin receptors decreases, total Bdnf mRNA levels, with distinct expression profiles of specific exons, in the hippocampus. Epigenetic analyses reveal that histone modifications, but not DNA methylation, underlie exon-specific transcription of the Bdnf gene induced by leptin. This is mediated by stimulation of AKT signaling, which in turn activates histone acetyltransferase p300 (p300 HAT), leading to changes in histone H3 acetylation and methylation at specific Bdnf promoters. Furthermore, deletion of Bdnf in the dentate gyrus, or specifically in LepRb-expressing neurons, abolishes the antidepressant-like effects of leptin. These findings indicate that leptin, acting via an AKT-p300 HAT epigenetic cascade, induces exon-specific Bdnf expression, which in turn is indispensable for leptin-induced antidepressant-like effects.

scholarly journals Distribution and Abundance of Messenger Ribonucleic Acid for Growth Hormone Receptor Isoforms in Human Tissues1

2000 ◽  
Vol 85 (8) ◽  
pp. 2865-2871
Author(s):  
Mercedes Ballesteros ◽  
Kin-Chuen Leung ◽  
Richard J. M. Ross ◽  
Tiina P. Iismaa ◽  
Ken K. Y. Ho
Keyword(s):  
Cell Lines ◽  
Ribonucleic Acid ◽  
Full Length ◽  
Liver Fat ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Messenger Ribonucleic Acid ◽  
Receptor Isoforms ◽  
Alternatively Spliced ◽  
Exon 9

Two alternatively spliced exon 9 variants of human GH receptor (GHR) messenger ribonucleic acid (mRNA), GHR-(1–279) and GHR-(1–277), were recently identified in liver. They encode receptor proteins lacking most of the intracellular domain and inhibit GH action in a dominant negative manner. Little is known about tissue distribution and abundance of these GHR isoforms. We have developed quantitative RT-PCR assays specific for the full-length and truncated GHRs and investigated their expression in various human tissues and cell lines. The mRNA of full-length GHR and GHR-(1–279) were readily detectable in all tissues investigated, with liver, fat, muscle, and kidney showing high levels of expression. These two receptor isoforms were also detected in a range of human cell lines, with strongest expression in IM9, a lymphoblastoid cell line. In contrast, GHR-(1–277) message was expressed at low levels in liver, fat, muscle, kidney, and prostate and in trace amount in IM9 cells. Full-length GHR was the most abundant isoform, accounting for over 90% of total receptor transcripts in liver, fat, and muscle for quantitative RT-PCR. However, liver had 2- to 4-fold more full-length receptor mRNA and 16- to 40-fold more GHR-(1–277) mRNA than fat and muscle, whereas the mRNA levels of GHR-(1–279) were similar in the three tissues. GHR-(1–279) constituted less than 4% in liver and 7–10% in fat and muscle. GHR-(1–277) accounted for 0.5% of total GHR transcripts in liver and less than 0.1% in the other two tissues. These data suggest that the absolute and relative abundance of mRNA of the three GHR isoforms may be tissue specific. The regulation of expression of exon 9 alternatively spliced GHR variants may provide a potential mechanism for modulation of GH sensitivity at the tissue level.

scholarly journals Leptin Signaling in the Hypothalamus during Chronic Central Leptin Infusion

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3789-3798 ◽  
Author(s):  
Rekha Pal ◽  
Abhiram Sahu
Keyword(s):  
Food Intake ◽  
Leptin Receptor ◽  
Binding Activity ◽  
Janus Kinase ◽  
Male Rats ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Leptin Signaling ◽  
Initial Decrease

Abstract Using a rat model of chronic central leptin infusion in which neuropeptide Y neurons develop leptin resistance, we examined whether leptin signal transduction mechanism in the hypothalamus is altered during central leptin infusion. Adult male rats were infused chronically into the lateral cerebroventricle with leptin (160 ng/h) or vehicle via Alzet pumps for 16 d. In the leptin-infused group, the initial decrease in food intake was followed by a recovery to their preleptin levels by d 16, although food intake remained significantly lower than in artificial cerebrospinal fluid controls; and body weight gradually decreased reaching a nadir at d 11 and remained stabilized at lower level thereafter. Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion. However, phosphorylated Janus kinase-2 was increased during the early part of leptin infusion but remained unaltered on d 16. Although hypothalamic suppressors of cytokine signaling-3 (SOCS3) mRNA levels were increased throughout leptin infusion, SOCS3 protein levels were increased only on d 16. This study demonstrates a sustained elevation in hypothalamic leptin receptor signaling through Janus kinase-STAT pathway despite an increased expression of SOCS3 during chronic central leptin infusion. We propose that an alteration in leptin signaling in the hypothalamus through pathways other than STAT3 and/or a defect in downstream of STAT3 signaling may be involved in food intake recovery seen after an initial decrease during chronic central leptin infusion.

scholarly journals HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms

2009 ◽  
Vol 296 (2) ◽  
pp. E291-E299 ◽  
Author(s):  
Christy L. White ◽  
Amy Whittington ◽  
Maria J. Barnes ◽  
Zhong Wang ◽  
George A. Bray ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Leptin Resistance ◽  
Whole Body ◽  
Mrna Levels ◽  
Protein Levels ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
Concomitant Reduction ◽  
Specific Deletion

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.

scholarly journals Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4880-4889 ◽  
Author(s):  
Heike Münzberg ◽  
Jeffrey S. Flier ◽  
Christian Bjørbæk
Keyword(s):  
High Fat Diet ◽  
Leptin Receptor ◽  
Elevated Serum ◽  
Brain Regions ◽  
Leptin Resistance ◽  
Hypothalamic Nucleus ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
High Fat ◽  
Suppressor Of Cytokine Signaling

Abstract Leptin resistance in diet-induced obese (DIO) mice is characterized by elevated serum leptin and a decreased response to exogenous leptin and is caused by unknown defects in the central nervous system. Leptin normally acts on several brain nuclei, but a detailed description of leptin resistance within individual brain regions has not been reported. We first mapped leptin-responsive cells in brains from DIO mice using phospho-signal transducer and activator of transcription (P-STAT3) immunohistochemistry. After 16 wk of high-fat-diet feeding, leptin-activated P-STAT3 staining within the arcuate nucleus (ARC) was dramatically decreased. In contrast, other hypothalamic and extrahypothalamic nuclei remained leptin sensitive. Reduced leptin-induced P-STAT3 in the ARC could also be detected after 4 wk and as early as 6 d of a high-fat diet. To examine potential mechanisms for leptin-resistant STAT3 activation in the ARC of DIO mice, we measured mRNA levels of candidate signaling molecules in the leptin receptor-STAT3 pathway. We found that the level of suppressor of cytokine signaling 3 (SOCS-3), an inhibitor of leptin signaling, is specifically increased in the ARC of DIO mice. The study suggests that the ARC is selectively leptin resistant in DIO mice and that this may be caused by elevated suppressor of cytokine signaling 3 in this hypothalamic nucleus. Defects in leptin action in the ARC may play a role in the pathogenesis of leptin-resistant obesity.

scholarly journals FRUCTOSE ALTERS THE EXPRESSION OF TYPE B LEPTIN RECEPTOR IN HYPHOTALAMUS AND INTESTINUM OF Rattus Novergicus

2018 ◽  
Vol 2 (2) ◽  
pp. 26
Author(s):  
Ermin Rachmawati ◽  
Risma Aprinda Kristanti ◽  
Nurlaili Susanti
Keyword(s):  
Insulin Resistance ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Intestinal Cell ◽  
Control Group ◽  
Type B ◽  
Leptin Receptors ◽  
Induce Insulin Resistance ◽  
Group 2 ◽  
Levene Test

<p><strong>Background</strong>: Several epidemiological data’s reported significant correlation between fructose consumption and diabetes mellitus type 2 by inducing insulin resistance. Leptin resistance induced by fructose was proposed as one novel mechanism that induce insulin resistance but the exact mechanism remains unclear.  We hypothesize that fructose diminish the type b leptin receptors in hypothalamus and intestine.</p><p><strong>Aim</strong>: This study was aimed to elucidate fructose effect on the expression of leptin receptor type b in hypothalamus and intestine of Rattus novergicus.</p><p><strong>Method</strong>: twenty eight rats were used and divided into 4 groups: Group 1 was control, group 2 was given fructose 10%, group 3 was given fructose 30% and group 4 was given fructose 55% for 2 months. At the end of treatment, the animal were sacrificed and then the hypothalamus and intestine were collected. The expression of type b leptin receptor were measured by immunohistochemistry technique with primary antibody from <em>Bioss antibodies type</em> <em>Leptin receptor polyclonal antibody bs-0109R using </em>Staining kit <em>Skytec Laboratories and DAB chromogen. </em>A positive expression can be seen as a brown colour in cell cytoplasm and counted in 100 cell. The expression then analysed using SPSS 18 with anova one way tes (p&lt;0,05) followed by post hoc test after the data showed normality and homogeneity using Saphiro wilk and Levene test (p&gt;0,05).</p><p><strong>Result</strong>: There was significant differences in type b leptin receptors found in hypothalamus between each group (p&lt;0.05). The significant differences also could be seen in the expression between control and group fructose 30 and 50% in intestinal cell (p&lt;0.05).</p><p><strong>Conclusion</strong>: the consumption of Fructose 55% for 2 months attenuates the expression of type b leptin receptors in hypothalamus and intestine of <em>R</em><em>at novergicus</em>.</p><p> </p>

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