Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice

Moon, Hee Sun; Dincer, Fadime; Mantzoros, Christos S.

doi:10.1007/s00125-012-2799-3

Cited by 25 publications

(13 citation statements)

References 42 publications

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“…Importantly, recent in vitro evidence has suggested that amylin activates signal transducer and activator of transcription 3 (STAT3), AMPK, and ERK signalling pathways in an additive fashion in hippocampal cells. Furthermore, amylin has been shown to decrease cell proliferation in a concentration‐dependent manner, although this effect is diminished following leptin administration and is dependent on STAT3/AMPK/ERK signalling . Because ERK is a significant downstream target mediating the physiological effects of amylin in pancreatic beta cells, amylin may also have beneficial effects on human physiology and pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Melanocortin 4 receptor–mediated effects of amylin on thermogenesis and regulation of food intake

Fan

et al. 2019

Diabetes Metabolism Res

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Aims: Amylin, a pancreatic hormone cosecreted with insulin, exerts important anorexic and weight-loss effects. Melanocortin 4 receptor (MC4R) signalling plays a critical role in energy homeostasis; however, its role on amylin-dependent regulation of food intake and adaptive thermogenesis of interscapular brown adipose tissue (IBAT) are unclear. In this study, we examined the effects of amylin on food intake and thermogenesis on IBAT via the MC4R pathway in mice. Materials and methods:Acute food consumption and thermogenesis in IBAT were measured in male wild-type (WT) and MC4R-deficient mice following intraperitoneal injection of amylin and SHU9119, an MC3R/4R antagonist, to determine the role of the central melanocortin system on the hypothalamus and IBAT. Results: Amylin (50 μg/kg) suppressed feeding and stimulated thermogenesis on IBAT via activation of the MC4R system in mice. Pharmacological blockade of MC4R using SHU9119 (50 μg/kg) attenuated amylin-induced inhibition of feeding and stimulation of thermogenesis in IBAT. No changes were observed when SHU9119 was injected alone. Moreover, amylin significantly increased MC4R expression and c-Fos neuronal signals in the arcuate nucleus and significantly increased acetyl-CoA carboxylase (ACC) phosphorylation in the hypothalamus and IBAT and uncoupling protein-1 (UCP1) expression in the IBAT of WT mice via the MC4R pathway. Conclusion: The melanocortin system was involved in amylin-induced suppression of food intake and activation of thermogenesis in both the hypothalamus and IBAT via modulation of ACC phosphorylation and UCP1 expression. KEYWORDS amylin, brown adipose tissue, food intake, hypothalamus, melanocortin 4 receptor, thermogenesis 1 | INTRODUCTION Studies of central nervous system (CNS) regulation of body temperature and thermogenesis have revealed that amylin exerts glucoselowering effects, promotes anorexia, and induces weight loss in both humans and rodents. 1,2 Amylin, a 37-amino acid peptide hormone cosecreted with insulin from pancreatic β-cells in response to nutrient ingestion, acts as a signal of satiation and adiposity, and circulating levels of amylin are higher in obese individuals than in normal-weight individuals. 3 These effects are triggered via amylin receptors in the area postrema (AP), and subsequent activation involves the solitary tract, lateral parabrachial nucleus, and other brain areas. 4Xiaojing Li and Kuikui Fan contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

Melanocortin 4 receptor–mediated effects of amylin on thermogenesis and regulation of food intake

Fan

et al. 2019

Diabetes Metabolism Res

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“…We have previously shown that STAT3/AMPK/ERK signaling is important for the maintenance of hippocampal development, which demonstrates that hippocampal neurogenesis, i.e., neurite outgrowth, and synaptogenesis are activated through STAT3/AMPK/ERK signaling pathways (19). Based on these findings, we explored whether irisin may activate STAT3/AMPK/ERK signaling in mouse HT19-7 HN cells.…”

Section: Discussionmentioning

confidence: 99%

“…The Western Blotting was performed as described previously (19). Measurement of signal intensity on nitrocellulose membranes after Western Blotting with various antibodies was performed using Image J processing and analysis software (http://rsbweb.nih.gov/ij/, August 25 th , 2011).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines

2013

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Aims/Hypothesis Irisin is a novel, myocyte secreted, hormone that has been proposed to mediate the beneficial effects of exercise on metabolism. Irisin is expressed, at lower levels, in human brains and knock-down of the precursor of irisin, FNDC5, decreases neural differentiation of mouse embryonic stem cells. No previous studies have evaluated whether irisin may directly regulate hippocampal neurogenesis in mouse hippocampal neuronal (HN) cells. Methods Hippocampal neurogenesis as well as irisin signaling were studied in vitro using mouse H19-7 HN cell lines. Results We observed that cell proliferation is regulated by irisin in a dose-dependent manner in mouse H19-7 HN cells. Specifically, physiological concentrations of irisin, 5 to 10 nM, had no effect on cell proliferation when compared to control. By contrast, pharmacological concentrations of irisin, 50 to 100 nM, increased cell proliferation when compared to control. Similar to these results regarding irisin’s effects on cell proliferation, we also observed that only pharmacological concentrations of irisin increased STAT3, but not AMPK and/or ERK, activation. Finally, we observed that irisin did not activate either microtubule-associated protein 2, a specific neurite outgrowth marker, or Synapsin, a specific synaptogenesis marker in mouse H19-7 HN cells. Conclusions/Interpretations Our data suggest that irisin, in pharmacological concentrations, increases cell proliferation in mouse H19-7 HN cells via STAT3, but not AMPK and/or ERK, signaling pathways. By contrast, neither physiological nor pharmacological concentrations of irisin alter markers of hippocampal neurogenesis in mouse H19-7 HN cell lines.

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“…These anti-inflammatory effects might.be involved in preventing the neuronal cell death caused by CPS. AMP-activated protein kinase (AMPK) regulates signalling pathways related to cell survival and apoptosis and plays a role in increasing hippocampal neurogenesis [33] . It has been argued that AMPK activation directly inhibits β-amyloid accumulation in vitro [34,35] .…”

Section: Discussionmentioning

confidence: 99%

Pioglitazonun NB2a Fare Nöroblastoma Hücre Kültürüdeki Nöroprotektif Etkisi

Vural¹,

Seyrek²

2018

Kafkas Univ Vet Fak Derg

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How to Cite This ArticleVural K, Seyrek O: The neuroprotective effect of pioglitazone on NB2a mouse neuroblastoma cell culture. AbstractPioglitazone (PGT) is a PPAR-γ activator that has neuroprotective properties via different mechanisms. It is thought to be neuroprotective in both acute and chronic use. Chlorpyrifos (CPS) is an Organophosphate insecticide that leads to attention deficit and cognitive problems in children and its neurotoxic effects are well known. This study aims to investigate the neuroprotective effects of PGT on CPS neurotoxicity in NB2a cell in the culture medium. We investigated the cell viability and proliferation using MTT assay and the percentage of neurite inhibition was analysed by measuring neurite outgrowth. Apoptosis was evaluated using the apoptotic index in TUNEL staining. Cell proliferation was found to be significantly reduced by CPS (25 µM), and this concentration-based reduction was prevented by PGT. Neurite outgrowth was inhibited by CPS (25 µM), whereas PGT significantly reversed neurite inhibition at and above 10 μM concentrations. The apoptotic index, which was increased using CPS (25 µM), was observed to reduce using PGT, depending on the concentration. Organophosphate is harmful to human health, and to our knowledge, there is no treatment. In individuals exposed to chlorpyrifos toxicity, acute toxic effects on neurons may be prevented or treated by PGT. ÖzPioglitazon (PGT), farklı mekanizmalar yoluyla nöroprotektif özelliklere sahip bir PPAR-γ aktivatörüdür. PGT akut ve kronik kullanımının nöroprotektif olduğu düşünülmektedir. Klorpirifos (CPS) çocuklarda dikkat eksikliği ve bilişsel problemlere yol açan bir organofosfat insektisit olup nörotoksik etkileri iyi bilinmektedir. Bu çalışmada, kültür ortamında fare kaynaklı NB2a kanser dizin hücrelerinde CPS nörotoksisitesi üzerine PGT'nin nöroprotektif etkileri olup olmadığının araştırdık. MTT analizini kullanarak hücre proliferasyonu üzerine etkilerini ve ılımlı nörotoksik etkinin bir göstergesi olan Nörotoksisite Tarama Testi ile % nörit inhibisyonu incelendi. Apopitoz, TUNEL boyamada apopitotik indeks kullanılarak değerlendirildi. CPS (25 μM) konsantrasyonda uygulandığında NB2a hücre proliferasyonu azalttı. PGT ise konsantrasyon bağlı olarak klorpirosa bağlı azalmayı önlendi. Klorpirifon 25 μM konsantrasyonda tama yakın Nörit uzamasını inhibe ederken, PGT 10 μM ve üzerindeki konsantrasyonlarda nörit inhibisyonunu önemli ölçüde engelledi. CFS (25 μM) ile artan apopitotik hücre sayısını, PGT 10 uM konsantarasyondan itibaren anlamlı düzeyde azalttığı görüldü. Organofosfatlar insan sağlığına zararlıdır ve toksik etkilerini önlemek için bildiğimiz bir tedavisi yoktur. Klorpirifos toksisitesine maruz kalan bireylerde, nöronlar üzerindeki akut toksik etkileri PGT ile önlenebilir veya tedavi edilebilir.

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Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice

Cited by 25 publications

References 42 publications

Melanocortin 4 receptor–mediated effects of amylin on thermogenesis and regulation of food intake

Melanocortin 4 receptor–mediated effects of amylin on thermogenesis and regulation of food intake

Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines

Pioglitazonun NB2a Fare Nöroblastoma Hücre Kültürüdeki Nöroprotektif Etkisi

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