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

Nature Communications
Mar QuiñonesRubén Nogueiras

Abstract

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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Citations

Apr 3, 2019·Nutrients·Cintia FolgueiraRubén Nogueiras
Nov 24, 2019·Reviews in Endocrine & Metabolic Disorders·Mar QuiñonesOmar Al-Massadi
Mar 2, 2019·Journal of the Endocrine Society·Sunil K PanigrahiSharon L Wardlaw
Dec 18, 2019·Journal of Physiology and Biochemistry·Ismael González-GarcíaCristina Contreras
Jan 11, 2020·Frontiers in Genetics·Raian E ContrerasPaul T Pfluger
Jun 14, 2019·Frontiers in Cellular Neuroscience·Débora SerrenhoAna Luísa Carvalho
Sep 3, 2020·Biomolecules·Toufic Kassouf, Grzegorz Sumara
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marlena M HolterBethany P Cummings
Mar 28, 2019·Frontiers in Endocrinology·Yi LiXue-Qun Chen
Oct 18, 2020·Nature Reviews. Endocrinology·Ivana NikolicGuadalupe Sabio
Sep 29, 2020·British Journal of Pharmacology·Miriam EjarqueSonia Fernández-Veledo
Dec 22, 2019·Brain, Behavior, and Immunity·Guilherme NogueiraLicio A Velloso
Jan 10, 2021·Biochemical Pharmacology·Zhifei XuPeihua Luo
Feb 13, 2021·International Journal of Molecular Sciences·Mar QuiñonesOmar Al Massadi
Nov 18, 2020·Diabetologia·Rubén Nogueiras, Guadalupe Sabio
Feb 7, 2021·International Journal of Molecular Sciences·Patricia Seoane-CollazoMiguel López
May 4, 2020·Neuroscience·Nathalia R V DraganoEdward Milbank
Mar 22, 2021·Redox Biology·Mar QuiñonesRuben Nogueiras
Oct 14, 2020·Neuroscience·Nathalia R V DraganoEdward Milbank

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Datasets Mentioned

BETA
GSE92707

Methods Mentioned

BETA
transgenic
protein folding
FACS
protein
NMR
ELISA
X-Ray

Software Mentioned

ImageJ Launcher
Frida
Graphpad
Graphpad Prism
Igor Pro
Spike2

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