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Title: Reduced alfa-MSH underlies hypothalamic ER-stress-induced hepatic gluconeogenesis
Author: Schneeberger, Marc
Gómez-Valadés, Alicia G.
Altirriba, Jordi
Sebastián Muñoz, David
Ramírez, Sara
Garcia, Ainhoa
Esteban, Yaiza
Drougard, Anne
Ferrés Coy, Albert
Bortolozzi Biasoni, Analía
García-Roves, Pablo M. (Pablo Miguel)
Jones, John G.
Manadas, Bruno
Zorzano Olarte, Antonio
Gomis, Ramon, 1946-
Claret, Marc
Keywords: Reticle endoplasmàtic
Metabolisme cel·lular
Endoplasmic reticulum
Cell metabolism
Issue Date: 9-Jul-2015
Publisher: Elsevier
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2015, vol. 12, num. 3, p. 361-370
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ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

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