RT Journal Article
T1 p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1.
A1 Quiñones, Mar
A1 Al-Massadi, Omar
A1 Folgueira, Cintia
A1 Bremser, Stephan
A1 Gallego, Rosalia
A1 Torres-Leal, Leonardo
A1 Haddad-Tovolli, Roberta
A1 Garcia-Caceres, Cristina
A1 Hernandez-Bautista, Rene
A1 Lam, Brian Y H
A1 Beiroa, Daniel
A1 Sanchez-Rebordelo, Estrella
A1 Senra, Ana
A1 Malagon, Jose A
A1 Valerio, Patricia
A1 Fondevila, Marcos F
A1 Fernø, Johan
A1 Malagon, Maria M
A1 Contreras, Raian
A1 Pfluger, Paul
A1 Brüning, Jens C
A1 Yeo, Giles
A1 Tschöp, Matthias
A1 Dieguez, Carlos
A1 Lopez, Miguel
A1 Claret, Marc
A1 Kloppenburg, Peter
A1 Sabio, Guadalupe
A1 Nogueiras, Ruben
K1 Adipose tissue, brown
K1 Agouti-related protein
K1 Animals
K1 Diet
K1 Hypothalamus
AB 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.
PB Nature Publishing Group
YR 2018
FD 2018-07-19
LK http://hdl.handle.net/10668/12869
UL http://hdl.handle.net/10668/12869
LA en
NO Quiñones M, Al-Massadi O, Folgueira C, Bremser S, Gallego R, Torres-Leal L, et al. p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1. Nat Commun. 2018 Aug 24;9(1):3432
NO This work has been supported by grants from Ministerio de Economia y Competitividad (C.D.: BFU2011-29102; M.L.: SAF2015-71026-R; and BFU2015-70454-REDT/Adipoplast; G.S.: SAF2016-79126-R; R.N.: BFU2015-70664R), Xunta de Galicia (M.L.: 2015-CP079 and 2016-PG068; R.N.: 2015-CP080 and 2016-PG057), Atresmedia Corporación (M.L.),Astra Zeneca Fundation (R.N.), the European Foundation for the Study of Diabetes (G.S. and R.N.), DFG grant SFB 1218/TP B07 (P.K.); Helse Vest RHF (J.F.; the Western Norway Regional Health Authority); Comunidad de Madrid IMMUNOTHERCAN-CM (B2017/BMD3733) (G.S.), Fundación BBVA (G.S.). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn). CIBERobn is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. The research leading to these results has also received funding from theEuropean Community’s Seventh Framework Programme under the following grant: ERC StG-2011-OBESITY53-281408 to R.N. M.Q. is a recipient of a Postdoctoral fellowship from Galician Government (Xunta de Galicia ED481B2014/039-0). R.H.-T. is a recipient of a postdoctoral fellowship FAPESP (Process: 2016/01868-2). O.A.-M. is funded by the ISCIII/SERGAS thought a research contract “Sara Borrell” (CD14/00091). E.S.-R. is recipient of a Predoctoral fellowship from Ministerio de Economia y Competitividad (ref: BES-2013-062796).
DS RISalud
RD Apr 9, 2025