Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding.
Cell
; 156(3): 495-509, 2014 Jan 30.
Article
en En
| MEDLINE
| ID: mdl-24462248
ABSTRACT
Maternal metabolic homeostasis exerts long-term effects on the offspring's health outcomes. Here, we demonstrate that maternal high-fat diet (HFD) feeding during lactation predisposes the offspring for obesity and impaired glucose homeostasis in mice, which is associated with an impairment of the hypothalamic melanocortin circuitry. Whereas the number and neuropeptide expression of anorexigenic proopiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP) neurons, electrophysiological properties of POMC neurons, and posttranslational processing of POMC remain unaffected in response to maternal HFD feeding during lactation, the formation of POMC and AgRP projections to hypothalamic target sites is severely impaired. Abrogating insulin action in POMC neurons of the offspring prevents altered POMC projections to the preautonomic paraventricular nucleus of the hypothalamus (PVH), pancreatic parasympathetic innervation, and impaired glucose-stimulated insulin secretion in response to maternal overnutrition. These experiments reveal a critical timing, when altered maternal metabolism disrupts metabolic homeostasis in the offspring via impairing neuronal projections, and show that abnormal insulin signaling contributes to this effect.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lactancia
/
Dieta Alta en Grasa
/
Hiperglucemia
/
Hipotálamo
/
Insulina
/
Obesidad
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Cell
Año:
2014
Tipo del documento:
Article