IRS2 signaling in LepR-b neurons suppresses FoxO1 to control energy balance independently of leptin action.
Cell Metab
; 15(5): 703-12, 2012 May 02.
Article
in En
| MEDLINE
| ID: mdl-22560222
ABSTRACT
Irs2-mediated insulin/IGF1 signaling in the CNS modulates energy balance and glucose homeostasis; however, the site for Irs2 function is unknown. The hormone leptin mediates energy balance by acting on leptin receptor (LepR-b)-expressing neurons. To determine whether LepR-b neurons mediate the metabolic actions of Irs2 in the brain, we utilized Lepr(cre) together with Irs2(L/L) to ablate Irs2 expression in LepR-b neurons (Lepr(ΔIrs2)). Lepr(ΔIrs2) mice developed obesity, glucose intolerance, and insulin resistance. Leptin action was not altered in young Lepr(ΔIrs2) mice, although insulin-stimulated FoxO1 nuclear exclusion was reduced in Lepr(ΔIrs2) mice. Indeed, deletion of Foxo1 from LepR-b neurons in Lepr(ΔIrs2) mice normalized energy balance, glucose homeostasis, and arcuate nucleus gene expression. Thus, Irs2 signaling in LepR-b neurons plays a crucial role in metabolic sensing and regulation. While not required for leptin action, Irs2 suppresses FoxO1 signaling in LepR-b neurons to promote energy balance and metabolism.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leptin
/
Forkhead Transcription Factors
/
Receptors, Leptin
/
Insulin Receptor Substrate Proteins
/
Neurons
Limits:
Animals
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2012
Document type:
Article
Affiliation country:
Estados Unidos