RESUMO
Sexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers "male-like" diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.
Assuntos
Neurônios/metabolismo , Fosfoproteínas/fisiologia , Pró-Opiomelanocortina/metabolismo , Caracteres Sexuais , Transativadores/fisiologia , Animais , Núcleo Arqueado do Hipotálamo/metabolismo , Peso Corporal , Metabolismo Energético/fisiologia , Estrogênios/metabolismo , Feminino , Homeostase , Hipotálamo/metabolismo , Masculino , Camundongos , Obesidade/metabolismo , Receptores para Leptina/metabolismo , Fatores SexuaisRESUMO
Medulloblastomas are among the most common malignant brain cancers in the pediatric population and consist of at least four distinct subgroups with unique molecular and genetic features and clinical outcomes. In this issue of Genes & Development, Niklison-Chirou and colleagues (pp. 1738-1753) identify the p53 family member and p73 isoform TAp73 as a crucial factor causing glutamine addiction in aggressive medulloblastomas. Their findings pave the way for the use of glutamine restriction as an adjuvant treatment for TAp73-expressing medulloblastomas.