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Denise D. Belsham - One of the best experts on this subject based on the ideXlab platform.

  • palmitate induces an anti inflammatory response in immortalized microglial bv 2 and img Cell Lines that decreases tnfα levels in mhypoe 46 Hypothalamic neurons in co culture
    Neuroendocrinology, 2018
    Co-Authors: Emma K Mcilwraith, Jennifer A Chalmers, Denise D. Belsham
    Abstract:

    BACKGROUND AND OBJECTIVES: Elevated levels of saturated fatty acids (SFA) induce a state of neuroinflammation in the hypothalamus. It has been suggested that microglia sense palmitate, a prevalent circulating SFA, and act as mediators of this inflammatory process by communicating with neurons, particularly those involved in appetite regulation. In this study, we examined the inflammatory response to palmitate in immortalized microglial Cell Lines, BV-2 and IMG, and the subsequent effects on inflammatory gene expression in a model of NPY/AgRP neurons, mHypoE-46. METHODS: The BV-2 Cells were treated with 50 µM palmitate for 4 and 24 h, and the transcriptional regulation of markers for inflammation and Cellular stress was assessed using an RT2 Profiler PCR Array. Select genes were verified with qRT-PCR. The BV-2 and IMG Cells were then co-cultured using 1.0-µm Cell culture inserts with an immortalized Hypothalamic Cell Line, mHypoE-46, to investigate potential interCellular communication between microglia and neurons. RESULTS: We found that palmitate increased the mRNA levels of specific inflammatory genes, and a general anti-inflammatory profile was revealed in the microglia Cells. The mRNA changes in TNFα at 4 and 24 h in BV-2 Cells were abrogated with the toll-like receptor 4 (TLR4) inhibitor, TAK-242, indicating the involvement of TLR4. Co-culture of mHypoE-46 neurons with microglia pre-treated with palmitate resulted in repression of TNFα expression in the Hypothalamic neurons. As palmitate significantly increased IL-13 expression in microglia, the effect of this cytokine was tested in mHypoE-46 neurons. The addition of IL-13 to neuronal cultures normalized the palmitate-mediated increase in IL-6 and AgRP expression, suggesting that microglia may protect surrounding neurons, at least in part, through the release of IL-13. CONCLUSIONS: These results suggest a potential anti-inflammatory role of microglia towards the palmitate-induced neuroinflammation, and potentially energy homeostasis, in Hypothalamic neurons.

  • glucose alters per2 rhythmicity independent of ampk whereas ampk inhibitor compound c causes profound repression of clock genes and agrp in mhypoe 37 Hypothalamic neurons
    PLOS ONE, 2016
    Co-Authors: Johanneke E Oosterman, Denise D. Belsham
    Abstract:

    Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, Hypothalamic Cell Line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation.

  • palmitate alters the rhythmic expression of molecular clock genes and orexigenic neuropeptide y mrna levels within immortalized Hypothalamic neurons
    Biochemical and Biophysical Research Communications, 2011
    Co-Authors: Laura J Fick, Denise D. Belsham, Gordon H Fick
    Abstract:

    The control of energy homeostasis within the hypothalamus is under the regulated control of homeostatic hormones, nutrients and the expression of neuropeptides that alter feeding behavior. Elevated levels of palmitate, a predominant saturated fatty acid in diet and fatty acid biosynthesis, alter Cellular function. For instance, a key mechanism involved in the development of insulin resistance is lipotoxicity, through increased circulating saturated fatty acids. Although many studies have begun to determine the underlying mechanisms of lipotoxicity in peripheral tissues, little is known about the effects of excess lipids in the brain. To determine these mechanisms we used an immortalized, clonal, Hypothalamic Cell Line, mHypoE-44, to demonstrate that palmitate directly alters the expression of molecular clock components, by increasing Bmal1 and Clock, or by decreasing Per2, and Rev-erbα, their mRNA levels and altering their rhythmic period within individual neurons. We found that these neurons endogenously express the orexigenic neuropeptides NPY and AgRP, thus we determined that palmitate administration alters the mRNA expression of these neuropeptides as well. Palmitate treatment causes a significant increase in NPY mRNA levels and significantly alters the phase of rhythmic expression. We explored the link between AMPK and the expression of neuropeptide Y using the AMPK inhibitor compound C and the AMP analog AICAR. AMPK inhibition decreased NPY mRNA. AICAR also elevated basal NPY, but prevented the palmitate-mediated increase in NPY mRNA levels. We postulate that this palmitate-mediated increase in NPY and AgRP synthesis may initiate a detrimental positive feedback loop leading to increased energy consumption.

  • estrogen facilitates both phosphatidylinositol 3 kinase akt and erk1 2 mitogen activated protein kinase membrane signaling required for long term neuropeptide y transcriptional regulation in clonal immortalized neurons
    The Journal of Neuroscience, 2008
    Co-Authors: Danny Titolo, Christopher M Mayer, Sandeep S Dhillon, Denise D. Belsham
    Abstract:

    It is established that increases in neuropeptide Y (NPY) expression are associated with hyperphagia and obesity. These effects can be reversed by estrogen, a recognized anorexigen. We found that 17β-estradiol (E2) regulates biphasic NPY gene expression in a clonal, immortalized Hypothalamic Cell Line, N-38, through estrogen receptor (ER) action at the level of the NPY promoter. However, rapid, nongenomic actions of estrogen, linked to the phosphatidylinositol 3-kinase (PI3-K)/Akt and ERK1/2 mitogen-activated protein kinase (MAPK) pathways, may also play a role. We therefore examined the changes in the phosphorylation status of Akt, ERK1/2, and cAMP response element-binding protein (CREB) after treatment with 10 nm E2 in the N-38 neurons and found activation of these signaling proteins within 5–30 min. We also demonstrated possible cross talk between the estrogen-activated PI3-K/Akt and MAPK/extraCellular signal-regulated kinase pathways using pharmacological inhibitors. We find that only ERα is involved in the early signaling events using the ERα agonist 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol and the ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile. Furthermore, we can detect colocalization of ERα and caveolin-1, a membrane-associated signaling protein. Remarkably, we find that the membrane-mediated events are critical for the long-term estrogen-mediated repression of NPY gene expression that can be mapped to within −97 bp of the NPY promoter. To link the early signaling events to downstream effectors, we detected induction of c-fos and inactivation of MSK-1 by estrogen and binding of CREB to this minimal promoter region. These observations suggest that rapid estrogen-mediated signaling is mediated by ERα, and the signal transduction events potentiate the genomic actions of estrogen on NPY gene expression in the N-38 NPY neurons.

  • Inhibition of Agouti-Related Peptide Expression by Glucose in a Clonal Hypothalamic Neuronal Cell Line Is Mediated by Glycolysis, Not Oxidative Phosphorylation
    Endocrinology, 2007
    Co-Authors: Hui Cheng, Fumiko Isoda, Denise D. Belsham, Charles V Mobbs
    Abstract:

    The regulation of neuroendocrine electrical activity and gene expression by glucose is mediated through several distinct metabolic pathways. Many studies have implicated AMP and ATP as key metabolites mediating neuroendocrine responses to glucose, especially through their effects on AMP-activated protein kinase (AMPK), but other studies have suggested that glycolysis, and in particular the cytoplasmic conversion of nicotinamide adenine dinucleotide (NAD+) to reduced NAD (NADH), may play a more important role than oxidative phosphorylation for some effects of glucose. To address these molecular mechanisms further, we have examined the regulation of agouti-related peptide (AgRP) in a clonal Hypothalamic Cell Line, N-38. AgRP expression was induced monotonically as glucose concentrations decreased from 10 to 0.5 mm glucose and with increasing concentrations of glycolytic inhibitors. However, neither pyruvate nor 3-β-hydroxybutyrate mimicked the effect of glucose to reduce AgRP mRNA, but on the contrary, prod...

Greti Aguilera - One of the best experts on this subject based on the ideXlab platform.

  • cyclic amp inducible early repressor mediates the termination of corticotropin releasing hormone transcription in Hypothalamic neurons
    Cellular and Molecular Neurobiology, 2009
    Co-Authors: Greti Aguilera
    Abstract:

    Elevations of inducible cAMP early repressor (ICER), the repressor isoform of the cAMP-responsive element modulator (CREM), are associated with protein binding to the corticotrophin releasing hormone (CRH) promoter and termination of CRH transcriptional responses to stress. To determine whether endogenous ICER production represses CRH transcription, we examined the effect of CREM siRNA on forskolin-stimulated ICER formation and CRH transcription in the Hypothalamic Cell Line, 4B, and in primary cultures of Hypothalamic neurons. Cotransfection of 4B Cells with CREM siRNA and a CRH promoter-driven luciferase reporter gene markedly reduced the induction of ICER by forskolin and potentiated the stimulatory effect of forskolin on CRH promoter activity, compared with Cells cotransfected with a nonspecific oligonucleotide. The role of ICER on endogenous CRH expression was studied in primary cultures of Hypothalamic neurons by examining the effect of CREM siRNA on forskolin-induced primary transcript (CRH hnRNA) using intronic real-time PCR. As observed during stress in vivo, forskolin-stimulated CRH hnRNA was transient, increasing up to 60 min and declining to near basal values by 3 h. Transfection of CREM siRNA reduced forskolin-induced ICER by about 45% 48-h later and partially reversed the declining phase of CRH hnRNA production at 3 h. The data provide evidence that endogenous ICER formation is required for termination of CRH transcription and support the hypothesis that ICER is part of an intraCellular feedback mechanism limiting the activation of CRH transcription during stress.

  • prolactin activates mitogen activated protein kinase signaling and corticotropin releasing hormone transcription in rat Hypothalamic neurons
    Endocrinology, 2009
    Co-Authors: Annegret Blume, Greti Aguilera, Luz Torner, Sivan Subburaju, Inga D Neumann
    Abstract:

    Prolactin (PRL) modulates maternal behavior and mediates Hypothalamic pituitary adrenal axis inhibition during lactation via PRL receptors in the brain. To identify mechanisms mediating these effects, we examined the effects of PRL on signaling and CRH transcription in Hypothalamic neurons in vivo and in vitro. Western blot of Hypothalamic proteins from rats receiving intracerebroventricular PRL injection revealed increases in phosphorylation of the MAPK and ERK. Double-staining immunohistochemistry demonstrated phosphorylated ERK localization in parvoCellular CRH neurons as well as magnoCellular vasopressin and oxytocin neurons of the Hypothalamic paraventricular (PVN) and supraoptic nuclei. PRL also induced ERK phosphorylation in vitro in the Hypothalamic Cell Line, 4B, which expresses PRL receptors, and in primary Hypothalamic neuronal cultures. Using reporter gene assays in 4B Cells, or quantitative RT-PCR for primary transcript in Hypothalamic Cell cultures, PRL potentiated forskolin-stimulated CRH transcription through activation of the ERK/MAPK pathway. The effect of PRL in Hypothalamic Cell cultures was unaffected by tetrodotoxin, suggesting a direct effect on CRH neurons. The data show that PRL activates the ERK/MAPK pathway and facilitates CRH transcription in CRH neurons, suggesting that the inhibitory effect of PRL on hypothalamo-pituitary-adrenal axis activity reported in vivo is indirect and probably mediated through modulation of afferent pathways to the PVN. In addition, the prominent stimulatory action of PRL on the ERK/MAPK pathway in the Hypothalamic PVN and supraoptic nucleus is likely to mediate neuroplasticity of the neuroendocrine system during lactation.

  • vasopressin increases gaga binding activity to the v1b receptor promoter through transactivation of the map kinase pathway
    Journal of Molecular Endocrinology, 2006
    Co-Authors: Simona Volpi, Ying Liu, Greti Aguilera
    Abstract:

    Previous studies show that binding of nuclear proteins to GAGA repeats (GAGA box) in the vasopressin type 1b receptor (V1bR) promoter is essential for transcriptional initiation of the gene. To determine whether increased vasopressin (VP) during stress activates V1bR expression through the GAGA box, we examined the effects of VP on GAGA binding activity and on the ability of the V1bR promoter to recruit RNA polymerase in the Hypothalamic Cell Line, H32. In chromatin immunoprecipitation assays, VP induced RNA polymerase II recruitment by the wild type V1bR promoter but not by a construct with the major GAGA box deletion. VP (10 min) also increased binding of nuclear proteins to radiolabeled GAGA oligonucleotides in electromobility shift assays. VP-induced GAGA binding activity was potentiated by the protein kinase C inhibitor, calphostin C, and was prevented by the MEK inhibitor, UO126, and the epidermal growth factor receptor (EGFR) inhibitor, AG1478, suggesting that VP activates GAGA binding through transactivation of the EGFR. This was confirmed by western blot experiments showing rapid increases in phospho ERK after incubation with VP, an effect that was potentiated by calphostin C and inhibited by UO12 and AG1478, as well as by the ability of VP to phosphorylate the EGFR. Using receptor selective VP analogs we showed that both V1aR and V1bR subtypes can mediate GAGA binding activation in H32 Cells. This study demonstrates that VP stimulates GAGA binding to the V1bR promoter through transactivation of the EGFR and MAP kinase. The data support the hypothesis that VP contributes to pituitary V1bR upregulation during stress through GAGA binding-mediated transcriptional activation.

  • inhibition of corticotrophin releasing hormone transcription by inducible camp early repressor in the Hypothalamic Cell Line 4b
    Journal of Neuroendocrinology, 2006
    Co-Authors: N Kalintchenko, Paolo Sassonecorsi, Greti Aguilera
    Abstract:

    : We have shown recently that the rapid decLine in corticotrophin-releasing hormone (CRH) transcription following activation by stress is associated with induction and binding to the CRH promoter of the repressor isoforms of cAMP responsive element modulator (CREM), inducible cAMP early repressor (ICER). The ability of ICER to inhibit CRH transcription was examined in the Hypothalamic Cell Line, 4B, which expresses CRH. Co-transfection of the inhibitory isoforms of CREM, ICER I and II and CREMbeta, and CRH promoter-luciferase constructs in 4B Cells blunted basal and forskolin-stimulated CRH promoter activity, an effect which was abolished by mutation of the CRE of the CRH promoter. Western blot analyses and electromobility gel-shift and super-shift showed increases in endogenous ICER after 3 h of incubation with forskolin. Consistent with an inhibitory effect of CREM on CRH transcription, chromatin immunoprecipitation assays in Cells transfected with ICER I revealed recruitment of CREM by the CRH promoter in conjunction with decreases in Pol II association. The study shows that generation of ICER following prolonged stimulation with forskolin, or transfection of an ICER expression vector in Hypothalamic Cell Lines expressing CRH, is associated with CREM binding to the CRH promoter and transcriptional repression. The data support the hypothesis that induction of repressor isoforms of CREM is part of an intraCellular feedback mechanism contributing to the termination of CRH transcription during stimulation.

  • corticotropin releasing hormone crh expression and protein kinase a mediated crh receptor signalling in an immortalized Hypothalamic Cell Line
    Journal of Neuroendocrinology, 2003
    Co-Authors: John Kasckow, Maria Nikodemova, Greti Aguilera, J J Mulchahey, Margareta D Pisarska, H C Chen, James P Herman, Erin K Murphy, Tilat A Rizvi, Frank M Dautzenberg
    Abstract:

    : Corticotropin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays an important role in the stress response in the hypothalamus. We describe the development of an immortalized Hypothalamic Cell Line which expresses CRH. We hypothesized that this Cell Line would possess the relevant characteristics of parvoCellular CRH-expressing neurones such as glucocorticoid receptor (GR) expression and vasopressin (VP) coexpression. For production of Hypothalamic Cells, embryonic day 19 rat pup hypothalami were dissected and dissociated into tissue culture dishes. They were immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene at 3 days of culture and then screened for expression of CRH following dilution cloning. One Cell Line was chosen (IVB) which exhibited CRH-like immunoreactivity (CRH-LI) and expressed CRH, VP and CRH1 receptor RNA via the reverse transcriptase-polymerase chain reaction. In addition, the Cell Line expressed the neuronal marker, microtubule-associated protein-2. We verified that the CRH-LI from IVB Cell lysates coeluted with CRH standard via reversed-phase high-performance liquid chromatography (HPLC). Furthermore, oxidation of the lysate converted its HPLC profile to that identical with oxidized CRH standard. In addition, IVB Cells exhibited high affinity binding to CRH. Incubation of IVB Cells with CRH lead to increases in cAMP levels and protein kinase A activity in a concentration-dependent manner. Incubation of IVB Cells with CRH also resulted in increases in phospho-cyclic-AMP response element binding protein (CREB) immunostaining as detected by immunocytochemical analysis. Finally, CRH treatment of IVB Cell Lines has been linked to CREB-mediated gene expression as determined via the PathDetect CREB trans-reporting system. The characteristics of IVB Cells, such as CRH and VP coexpression, GR expression and a biologically active CRH-R1-mediated signalling pathway, suggest that this neuronal Cell Line may serve as model of parvoCellular CRH neurones.

Pamela L Mellon - One of the best experts on this subject based on the ideXlab platform.

  • Cellular/Molecular Circadian Gene Expression Regulates Pulsatile Gonadotropin-Releasing Hormone (GnRH) Secretory Patterns in the Hypothalamic GnRH-Secreting GT1–7
    2015
    Co-Authors: Cell Line, Rachel S White, Pamela L Mellon
    Abstract:

    Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and Cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1–7 mouse Hypothalamic Cell Line as a model for GnRH secretion, because these Cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investi-gated the role of the molecular circadian clock in regulation of GnRH secretion. GT1–7 Cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1–7 Cells by transient expression of the dominant-negative Clock-19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1–7 Cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these Cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endog-enous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion

  • circadian gene expression regulates pulsatile gonadotropin releasing hormone gnrh secretory patterns in the Hypothalamic gnrh secreting gt1 7 Cell Line
    The Journal of Neuroscience, 2003
    Co-Authors: Patrick E Chappell, Rachel S White, Pamela L Mellon
    Abstract:

    Although it has long been established that episodic secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is required for normal gonadotropin release, the molecular and Cellular mechanisms underlying the synchronous release of GnRH are primarily unknown. We used the GT1‐7 mouse Hypothalamic Cell Line as a model for GnRH secretion, because these Cells release GnRH in a pulsatile pattern similar to that observed in vivo. To explore possible molecular mechanisms governing secretory timing, we investigated the role of the molecular circadian clock in regulation of GnRH secretion. GT1‐7 Cells express many known core circadian clock genes, and we demonstrate that oscillations of these components can be induced by stimuli such as serum and the adenylyl cyclase activator forskolin, similar to effects observed in fibroblasts. Strikingly, perturbation of circadian clock function in GT1‐7 Cells by transient expression of the dominant-negative Clock-19 gene disrupts normal ultradian patterns of GnRH secretion, significantly decreasing mean pulse frequency. Additionally, overexpression of the negative limb clock gene mCry1 in GT1‐7 Cells substantially increases GnRH pulse amplitude without a commensurate change in pulse frequency, demonstrating that an endogenous biological clock is coupled to the mechanism of neurosecretion in these Cells and can regulate multiple secretory parameters. Finally, mice harboring a somatic mutation in the Clock gene are subfertile and exhibit a substantial increase in estrous cycle duration as revealed by examination of vaginal cytology. This effect persists in normal light/dark (LD) cycles, suggesting that a suprachiasmatic nucleus-independent endogenous clock in GnRH neurons is required for eliciting normal pulsatile patterns of GnRH secretion.

  • neuron specific expression in vivo by defined transcription regulatory elements of the gnrh gene
    Endocrinology, 2002
    Co-Authors: Mark A Lawson, Leigh A Macconell, Jinah Kim, Brian T Powl, Shelley B Nelson, Pamela L Mellon
    Abstract:

    The GnRH-expressing neurons are the ultimate regulator of reproductive function. GnRH gene expression is limited to this small population of neurons in the hypothalamus. Transfections using 3 kb of the rat or mouse 5'-regulatory region provide specific gene expression in the Hypothalamic Cell Line GT1-7. The combination of two elements, a 300-bp enhancer and a 173-bp promoter, recapitulates specificity in GT1-7 Cells. It was not known whether these elements could specifically target gene expression throughout development in the whole animal. We demonstrate that the 3-kb rat GnRH regulatory region provides a higher degree of specificity than the equivalent mouse sequence in a mouse Hypothalamic Cell Line. Moreover, combination of the enhancer and the promoter of the rat gene targets expression to GnRH neurons in transgenic mice in a developmentally appropriate manner. Transgene expression is regulated by activin A, a known activator of GnRH gene expression. In contrast, the enhancer on a heterologous promoter produces inappropriate expression in vivo. We conclude that the enhancer and promoter regions of the rat GnRH gene are necessary for targeted expression to Hypothalamic neurons and are sufficient to confer regulated, Cell type-specific expression to a reporter gene in vivo.

Fei Hua - One of the best experts on this subject based on the ideXlab platform.

  • salubrinal abrogates palmitate induced leptin resistance and endoplasmic reticulum stress via nuclear factor kappa light chain enhancer of activated b Cell pathway in mhypoe 44 Hypothalamic neurons
    Diabetes Metabolic Syndrome and Obesity: Targets and Therapy, 2018
    Co-Authors: Min Zhang, Xiaohong Jiang, Qi Sha, Fei Hua
    Abstract:

    Background The prevalence of obesity is growing rapidly and has become a global problem that increases the risk for many diseases. It is influenced by many factors, including consumption of the Western-style diet, characterized as a high-fat diet. Within the central nervous system, the hypothalamus is a critical site in maintaining energy homeostasis and sensing nutrient status, including palmitate, the major component of high-fat-diet. Methods In the present study, we conducted a variety of studies to investigate the specific role of salubrinal on palmitate-induced Hypothalamic Cell death, leptin signaling, and ER stress in an embryonic Hypothalamic Cell Line. Experiments were also performed to identify the underlying mechanisms of the protective effect of salubrinal. Results Our results indicate that salubrinal protects Hypothalamic Cells against PA-induced ER stress and improves Hypothalamic leptin sensitivity. Conclusion Taken together, our findings conclusively reveal that salubrinal abrogates palmitate-induced Hypothalamic leptin resistance and ER stress via NF-κB pathway.

Min Zhang - One of the best experts on this subject based on the ideXlab platform.

  • salubrinal abrogates palmitate induced leptin resistance and endoplasmic reticulum stress via nuclear factor kappa light chain enhancer of activated b Cell pathway in mhypoe 44 Hypothalamic neurons
    Diabetes Metabolic Syndrome and Obesity: Targets and Therapy, 2018
    Co-Authors: Min Zhang, Xiaohong Jiang, Qi Sha, Fei Hua
    Abstract:

    Background The prevalence of obesity is growing rapidly and has become a global problem that increases the risk for many diseases. It is influenced by many factors, including consumption of the Western-style diet, characterized as a high-fat diet. Within the central nervous system, the hypothalamus is a critical site in maintaining energy homeostasis and sensing nutrient status, including palmitate, the major component of high-fat-diet. Methods In the present study, we conducted a variety of studies to investigate the specific role of salubrinal on palmitate-induced Hypothalamic Cell death, leptin signaling, and ER stress in an embryonic Hypothalamic Cell Line. Experiments were also performed to identify the underlying mechanisms of the protective effect of salubrinal. Results Our results indicate that salubrinal protects Hypothalamic Cells against PA-induced ER stress and improves Hypothalamic leptin sensitivity. Conclusion Taken together, our findings conclusively reveal that salubrinal abrogates palmitate-induced Hypothalamic leptin resistance and ER stress via NF-κB pathway.