AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.
Cell
; 165(1): 125-138, 2016 Mar 24.
Article
em En
| MEDLINE
| ID: mdl-27015310
ABSTRACT
Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP â LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP â anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP â aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação do Apetite
/
Tecido Adiposo Marrom
/
Resistência à Insulina
/
Glucose
/
Neurônios
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2016
Tipo de documento:
Article