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Quiñones, M.* ; Al-Massadi, O.* ; Folgueira, C.* ; Bremser, S.* ; Gallego, R.* ; Torres-Leal, L.* ; Haddad-Tóvolli, R.* ; García-Cáceres, C. ; Hernandez-Bautista, R.* ; Lam, B.Y.H.* ; Beiroa, D.* ; Sanchez-Rebordelo, E.* ; Senra, A.* ; Malagon, J.A.* ; Valerio, P.* ; Fondevila, M.F.* ; Fernø, J.* ; Malagon, M.M.* ; Contreras, R. ; Pfluger, P.T. ; Brüning, J.C.* ; Yeo, G.* ; Tschöp, M.H. ; Diéguez, C.* ; López, M.* ; Claret, M.* ; Kloppenburg, P.* ; Sabio, G.* ; Nogueiras, R.*

p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1.

Nat. Commun. 9:3432 (2018)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
p53 is a well-known tumor suppressor that has emerged as an important player in energy balance. However, its metabolic role in the hypothalamus remains unknown. Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity. AgRP-specific ablation of p53 resulted in increased hypothalamic c-Jun N-terminal kinase (JNK) activity before the mice developed obesity, and central inhibition of JNK reversed the obese phenotype of these mice. The overexpression of p53 in the ARC or specifically in AgRP neurons of obese mice decreased body weight and stimulated BAT thermogenesis, resulting in body weight loss. Finally, p53 in AgRP neurons regulates the ghrelin-induced food intake and body weight. Overall, our findings provide evidence that p53 in AgRP neurons is required for normal adaptations against diet-induced obesity.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Agouti-related Peptide; Adipose-tissue Thermogenesis; Regulates Food-intake; Connects Er Stress; Energy-balance; Endoplasmic-reticulum; Hypothalamic Ampk; Glucose-homeostasis; Pomc Neurons; Metabolic-regulation
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 9, Issue: 1, Pages: , Article Number: 3432 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed