IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
artículos
Título:
Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin post-translational processing
Autor/es:
CAKIR I; CYR NE; PERELLO M; LITVINOV LB; ROMERO A; STUART R; NILLNI EA
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Lugar: Bethesda, Maryland; Año: 2013 p. 17675 - 17688
ISSN:
0021-9258
Resumen:
It was shown previously that abnormal prohormone processing or inactive
proconverting enzymes that are responsible for this processing cause
profound obesity. Our laboratory demonstrated earlier that in the
diet-induced obesity (DIO) state, the appetite-suppressing neuropeptide
α-melanocyte-stimulating hormone (α-MSH) is reduced, yet the mRNA of its
precursor protein proopiomelanocortin (POMC) remained unaltered. It was
also shown that the DIO condition promotes the development of
endoplasmic reticulum (ER) stress and leptin resistance. In the current
study, using an in vivo model combined with in vitro experiments, we
demonstrate that obesity-induced ER stress obstructs the
post-translational processing of POMC by decreasing proconverting enzyme
2, which catalyzes the conversion of adrenocorticotropin to α-MSH,
thereby decreasing α-MSH peptide production. This novel mechanism of ER
stress affecting POMC processing in DIO highlights the importance of ER
stress in regulating central energy balance in obesity