TY - JOUR AU - Ruska, Yvette Magdolna AU - Péterfi, Zoltán Attila AU - Stiftné Szilvásy-Szabó, Anett AU - Kővári, Dóra AU - Hrabovszky, Erik AU - Dorogházi, Beáta Vanessza AU - Gereben, Balázs AU - Tóth, Blanka AU - Matziari, Magdalini AU - Wittmann, Gábor AU - Fekete, Csaba TI - GLP-1 Receptor Signaling Has Different Effects on the Perikarya and Axons of the Hypophysiotropic Thyrotropin-Releasing Hormone Synthesizing Neurons in Male Mice JF - THYROID J2 - THYROID VL - 34 PY - 2024 IS - 2 SP - 252 EP - 260 PG - 9 SN - 1050-7256 DO - 10.1089/thy.2023.0284 UR - https://m2.mtmt.hu/api/publication/34578220 ID - 34578220 AB - Background: Glucagon-like peptide 1 (GLP-1) is involved in the regulation of energy and glucose homeostasis. As GLP-1 has similar effects on the energy homeostasis as the hypophysiotropic thyrotropin-releasing hormone (TRH) neurons that regulate the hypothalamic-pituitary-thyroid (HPT) axis, we raised the possibility that the TRH neurons are involved in the mediation of the effects of GLP-1. Therefore, the relationship and interaction of the GLP-1 system and the TRH neurons of the hypothalamic paraventricular nucleus (PVN) were studied.Methods: To examine the anatomical and functional relationship of TRH neurons and the GLP-1 system in the PVN, immunocytochemistry, in situ hybridization, in vitro patch-clamp electrophysiology, metabolic phenotyping, and explant experiments were performed.Results: Our data demonstrate that the TRH neurons of the PVN are innervated by GLP-1 producing neurons and express the GLP-1 receptor (GLP-1R). However, not only do the GLP-1-innervated TRH neurons express GLP-1R but the receptor is also present in the axons of the hypophysiotropic TRH neurons in the blood-brain barrier free median eminence (ME) suggesting that peripherally derived GLP-1 may also influence the TRH neurons. In vitro, GLP-1 increased the firing rate of TRH neurons and depolarized them. In addition, GLP-1 directly stimulated the GABAergic input of a population of TRH neurons. Furthermore, GLP-1 inhibited the release of TRH from the hypophysiotropic axons in the ME. In vivo, peripheral GLP-1R agonist administration markedly inhibited the food intake and the energy expenditure, but had no effect on the TRH expression in the PVN and resulted in lower circulating free T4 levels.Conclusions: Our results indicate that GLP-1R activation has a direct stimulatory effect on TRH neurons in the PVN, but the activation of GLP-1R may also inhibit TRH neurons by facilitating their inhibitory inputs or by inhibiting the axon terminals of these cells in the ME. The innervation of TRH neurons by GLP-1 neurons suggests that TRH neurons might be influenced by both circulating GLP-1 and by GLP-1 neurons of the nucleus tractus solitarii. The lack of GLP-1R agonist-induced regulation of TRH neurons in vivo suggests that the HPT axis does not mediate the GLP-1R agonist-induced weight loss. LA - English DB - MTMT ER - TY - JOUR AU - Petersen, Julian AU - Englmaier, Lukas AU - Artemov, Artem V. AU - Poverennaya, Irina AU - Mahmoud, Ruba AU - Bouderlique, Thibault AU - Tesarova, Marketa AU - Deviatiiarov, Ruslan AU - Stiftné Szilvásy-Szabó, Anett AU - Akkuratov, Evgeny E. AU - Pajuelo Reguera, David AU - Zeberg, Hugo AU - Kaucka, Marketa AU - Kastriti, Maria Eleni AU - Krivanek, Jan AU - Radaszkiewicz, Tomasz AU - Gömöryová, Kristína AU - Knauth, Sarah AU - Potesil, David AU - Zdrahal, Zbynek AU - Ganji, Ranjani Sri AU - Grabowski, Anna AU - Buhl, Miriam E. AU - Zikmund, Tomas AU - Kavkova, Michaela AU - Axelson, Håkan AU - Lindgren, David AU - Kramann, Rafael AU - Kuppe, Christoph AU - Erdélyi, Ferenc AU - Máté, Zoltán AU - Szabó, Gábor AU - Koehne, Till AU - Harkany, Tibor AU - Fried, Kaj AU - Kaiser, Jozef AU - Boor, Peter AU - Fekete, Csaba AU - Rozman, Jan AU - Kasparek, Petr AU - Prochazka, Jan AU - Sedlacek, Radislav AU - Bryja, Vitezslav AU - Gusev, Oleg AU - Adameyko, Igor TI - A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 14 PY - 2023 IS - 1 PG - 22 SN - 2041-1723 DO - 10.1038/s41467-023-38663-7 UR - https://m2.mtmt.hu/api/publication/34729392 ID - 34729392 AB - In this study we use comparative genomics to uncover a gene with uncharacterized function ( 1700011H14Rik/C14orf105/CCDC198 ), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes. LA - English DB - MTMT ER - TY - JOUR AU - Sinkó, Richárd AU - Mohácsik, Petra AU - Fekete, Csaba AU - Gereben, Balázs TI - In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse JF - JOVE-JOURNAL OF VISUALIZED EXPERIMENTS J2 - JOVE-J VIS EXP VL - 2023 PY - 2023 IS - 200 PG - 10 SN - 1940-087X DO - 10.3791/65657 UR - https://m2.mtmt.hu/api/publication/34232164 ID - 34232164 LA - English DB - MTMT ER - TY - JOUR AU - Petersen, Julian AU - Englmaier, Lukas AU - Artemov, Artem V. AU - Poverennaya, Irina AU - Mahmoud, Ruba AU - Bouderlique, Thibault AU - Tesarova, Marketa AU - Deviatiiarov, Ruslan AU - Stiftné Szilvásy-Szabó, Anett AU - Akkuratov, Evgeny E. AU - Pajuelo Reguera, David AU - Zeberg, Hugo AU - Kaucka, Marketa AU - Kastriti, Maria Eleni AU - Krivanek, Jan AU - Radaszkiewicz, Tomasz AU - Gömöryová, Kristína AU - Knauth, Sarah AU - Potesil, David AU - Zdrahal, Zbynek AU - Ganji, Ranjani Sri AU - Grabowski, Anna AU - Buhl, Miriam E. AU - Zikmund, Tomas AU - Kavkova, Michaela AU - Axelson, Håkan AU - Lindgren, David AU - Kramann, Rafael AU - Kuppe, Christoph AU - Erdélyi, Ferenc AU - Máté, Zoltán AU - Szabó, Gábor AU - Koehne, Till AU - Harkany, Tibor AU - Fried, Kaj AU - Kaiser, Jozef AU - Boor, Peter AU - Fekete, Csaba AU - Rozman, Jan AU - Kasparek, Petr AU - Prochazka, Jan AU - Sedlacek, Radislav AU - Bryja, Vitezslav AU - Gusev, Oleg AU - Adameyko, Igor TI - Author Correction: A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 14 PY - 2023 IS - 1 SN - 2041-1723 DO - 10.1038/s41467-023-39373-w UR - https://m2.mtmt.hu/api/publication/34038280 ID - 34038280 LA - English DB - MTMT ER - TY - JOUR AU - Salas-Lucia, Federico AU - Fekete, Csaba AU - Sinkó, Richárd AU - Egri, Péter AU - Rada, Kristóf Róbert AU - Ruska, Yvette Magdolna AU - Gereben, Balázs AU - Bianco, Antonio TI - Axonal T3 uptake and transport can trigger thyroid hormone signaling in the brain JF - ELIFE J2 - ELIFE VL - 12 PY - 2023 PG - 18 SN - 2050-084X DO - 10.7554/eLife.82683 UR - https://m2.mtmt.hu/api/publication/33917113 ID - 33917113 AB - The development of the brain, as well as mood and cognitive functions, are affected by thyroid hormone (TH) signaling. Neurons are the critical cellular target for TH action, with T3 regulating the expression of important neuronal gene sets. However, the steps involved in T3 signaling remain poorly known given that neurons express high levels of type 3 deiodinase (D3), which inactivates both T4 and T3. To investigate this mechanism, we used a compartmentalized microfluid device and identified a novel neuronal pathway of T3 transport and action that involves axonal T3 uptake into clathrin-dependent, endosomal/non-degradative lysosomes (NDLs). NDLs-containing T3 are retrogradely transported via microtubules, delivering T3 to the cell nucleus, and doubling the expression of a T3-responsive reporter gene. The NDLs also contain the monocarboxylate transporter 8 (Mct8) and D3, which transport and inactivate T3, respectively. Notwithstanding, T3 gets away from degradation because D3's active center is in the cytosol. Moreover, we used a unique mouse system to show that T3 implanted in specific brain areas can trigger selective signaling in distant locations, as far as the contralateral hemisphere. These findings provide a pathway for L-T3 to reach neurons and resolve the paradox of T3 signaling in the brain amid high D3 activity. LA - English DB - MTMT ER - TY - CONF AU - Szabó, Adrienn AU - Farkas, Szidónia AU - Török, Bibiána AU - Correia, Pedro AU - Kovács, T AU - Kádár, Andrea AU - Hegedűs, P AU - Fekete, Csaba AU - Zelena, Dóra TI - Enhanced food intake and abnormal deiodinase mRNA expression pattern in the triple transgenic Alzheimer’s disease model mice T2 - 6th Hungarian Neuroscience Doctoral Conference for Undergraduate Students, Graduate Students and Junior Postdoc PY - 2023 SP - 29; 93 UR - https://m2.mtmt.hu/api/publication/33629260 ID - 33629260 LA - English DB - MTMT ER - TY - CONF AU - Szabó, Adrienn AU - Farkas, Szidónia AU - Török, Bibiána AU - Correia, Pedro AU - Kovács, T AU - Kádár, Andrea AU - Hegedűs, P AU - Fekete, Csaba AU - Zelena, Dóra TI - Enhanced food intake and abnormal deiodinase mRNA expression pattern in the triple transgenic Alzheimer’s disease model mice T2 - Joint Neuroscience Meeting of the Hungarian Neuroscience Society (MITT) & the Austrian Neuroscience Association (ANA) PY - 2023 UR - https://m2.mtmt.hu/api/publication/33628989 ID - 33628989 N1 - Poster LA - English DB - MTMT ER - TY - JOUR AU - Kozsurek, Márk AU - Király, Kornél P AU - Gyimesi, Klára AU - Lukácsi, Erika AU - Fekete, Csaba AU - Gereben, Balázs AU - Mohácsik, Petra AU - Helyes, Zsuzsanna AU - Bölcskei, Kata AU - Tékus, Valéria AU - Pap, Károly AU - Szűcs, Edina AU - Benyhe, Sándor AU - Imre, Timea AU - Szabó, Pál Tamás AU - Gajtkó, Andrea AU - Szentesiné Holló, Krisztina AU - Puskár, Zita TI - Unique, Specific CART Receptor-Independent Regulatory Mechanism of CART(55-102) Peptide in Spinal Nociceptive Transmission and Its Relation to Dipeptidyl-Peptidase 4 (DDP4) JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 2 PG - 25 SN - 1661-6596 DO - 10.3390/ijms24020918 UR - https://m2.mtmt.hu/api/publication/33560486 ID - 33560486 AB - Cocaine- and amphetamine-regulated transcript (CART) peptides are involved in several physiological and pathological processes, but their mechanism of action is unrevealed due to the lack of identified receptor(s). We provided evidence for the antihyperalgesic effect of CART(55-102) by inhibiting dipeptidyl-peptidase 4 (DPP4) in astrocytes and consequently reducing neuroinflammation in the rat spinal dorsal horn in a carrageenan-evoked inflammation model. Both naturally occurring CART(55-102) and CART(62-102) peptides are present in the spinal cord. CART(55-102) is not involved in acute nociception but regulates spinal pain transmission during peripheral inflammation. While the full-length peptide with a globular motif contributes to hyperalgesia, its N-terminal inhibits this process. Although the anti-hyperalgesic effects of CART(55-102), CART(55-76), and CART(62-76) are blocked by opioid receptor antagonists in our inflammatory models, but not in neuropathic Seltzer model, none of them bind to any opioid or G-protein coupled receptors. DPP4 interacts with Toll-like receptor 4 (TLR4) signalling in spinal astrocytes and enhances the TLR4-induced expression of interleukin-6 and tumour necrosis factor alpha contributing to inflammatory pain. Depending on the state of inflammation, CART(55-102) is processed in the spinal cord, resulting in the generation of biologically active isoleucine-proline-isoleucine (IPI) tripeptide, which inhibits DPP4, leading to significantly decreased glia-derived cytokine production and hyperalgesia. LA - English DB - MTMT ER - TY - JOUR AU - Sinkó, Richárd AU - Mohácsik, Petra AU - Kővári, Dóra AU - Penksza, Veronika AU - Wittmann, Gábor AU - Borbélyné Mácsai, Lilla AU - Fonseca, Tatiana L AU - Bianco, Antonio Carlos AU - Fekete, Csaba AU - Gereben, Balázs TI - Different hypothalamic mechanisms control decreased circulating thyroid hormone levels in infection and fasting-induced Non-Thyroidal Illness Syndrome in male Thyroid Hormone Action Indicator Mice JF - THYROID J2 - THYROID VL - 33 PY - 2023 IS - 1 SP - 109 EP - 118 PG - 10 SN - 1050-7256 DO - 10.1089/thy.2022.0404 UR - https://m2.mtmt.hu/api/publication/33208795 ID - 33208795 LA - English DB - MTMT ER - TY - CONF AU - Durst, Máté AU - Könczöl, Katalin AU - Ocskay, Klementina AU - Sípos, Klaudia AU - Stiftné Szilvásy-Szabó, Anett AU - Fekete, Csaba AU - Tóth, Zsuzsanna TI - Role of nesfatin-1 neuropeptide in metabolic changes following intrauterine undernutrition T2 - International Neuroscience Meeting, Budapest 2022 PY - 2022 UR - https://m2.mtmt.hu/api/publication/33780216 ID - 33780216 LA - English DB - MTMT ER -