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Título: | Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis | Autor: | Schneeberger, Marc Gómez-Valadés, Alicia G. Altirriba, Jordi Sebastián, David Ramírez, Sara Garcia, Ainhoa Esteban, Yaiza Drougard, Anne Ferrés-Coy, Albert Bortolozzi, Analía Garcia-Roves, Pablo M. Jones, John G. Manadas, Bruno Zorzano, Antonio Gomis, Ramon Claret, Marc |
Data: | 21-Jul-2015 | Editora: | Elsevier | Projeto: | This work has been supported by grants PI10/ 01074 (to M.C.), PI13/01604 (to M.C.), and PI13/01390 (to A.B.; Plan Estatal de I+D+I 2013-2016) cofunded by ISCIII-Subdireccio´ n General de Investigacio´n y Fomento de la Investigacio´ n el Fondo Europeo de Desarrollo Regional (FEDER); RecerCaixa 2010ACUP_00275 (to M.C.); Generalitat de Catalunya 2014SGR659 (to R.G.) and 2014SGR48 (to A.Z.); Ministerio de Ciencia y Competitividad SAF2013-40987R (to A.Z.); Marie Curie People Cofund Fellowship, Seventh Framework Programme of the European Commission grant 267248:DIATRAIN (to A.G.G.-V.); and co-funding from Fundac¸ a˜ o para a Ci^encia e a Tecnologia (FCT) and FEDER through COMPETE programme for grants REDE/1506/REM/2005 (National Mass Spectrometry Network), RECI/QEQQFI/ 0168/2012 (UC-NMR Center), EXCL/DTP-PIC/0069/2012, and structural funding for the Center for Neurosciences (PEst-C/SAU/LA0001/2011; to J.G.J. and B.M.). M.S. is a recipient of an undergraduate grant from the UB. A.F.-C. is a recipient of a fellowship from Spanish Ministry of Education, Culture and Sport. M.C. is a recipient of a Miguel Servet contract (MICINN-ISCIII; CP09/00233). P.M.G.-R. is a recipient of a Ramon y Cajal contract (MICINN; RYC-2009-05158). A.Z. is a recipient of an ICREA Acade` mia (Generalitat de Catalunya). This work was carried out in part at the Esther Koplowitz Centre. | Título da revista, periódico, livro ou evento: | Cell Reports | Volume: | 12 | Número: | 3 | Resumo: | Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. | URI: | https://hdl.handle.net/10316/109087 | ISSN: | 22111247 | DOI: | 10.1016/j.celrep.2015.06.041 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.pdf | 3.06 MB | Adobe PDF | Ver/Abrir |
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