2026-07-21T16:08:17Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65362024-09-27T08:20:33Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Quinones, Mar author Al-Massadi, Omar author Folgueira, Cintia author Bremser, Stephan author Gallego, Rosalia author Torres-Leal, Leonardo author Haddad-Tovolli, Roberta author Garcia-Caceres, Cristina author Hernandez-Bautista, Rene author Lam, Brian Y. H. author Beiroa, Daniel author Sanchez-Rebordelo, Estrella author Senra, Ana author Malagon, Jose A. author Valerio, Patricia author Fondevila, Marcos F. author Ferno, Johan author Malagon, Maria M. author Contreras, Raian author Pfluger, Paul author Bruening, Jens C. author Yeo, Giles author Tschoep, Matthias author Dieguez, Carlos author Lopez, Miguel author Claret, Marc author Kloppenburg, Peter author Sabio, Guadalupe author Nogueiras, Ruben author 2018 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. Nat Commun. 2018; 9(1):3432 10.1038/s41467-018-05711-6 2041-1723 Nature Communications 30143607 http://hdl.handle.net/20.500.12105/6536 AGOUTI-RELATED PEPTIDE ADIPOSE-TISSUE THERMOGENESIS REGULATES FOOD-INTAKE CONNECTS ER STRESS ENERGY-BALANCE ENDOPLASMIC-RETICULUM HYPOTHALAMIC AMPK GLUCOSE-HOMEOSTASIS POMC NEURONS METABOLIC-REGULATION p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1