Ire1α in Pomc Neurons Is Required for Thermogenesis and Glycemia.
Diabetes
; 66(3): 663-673, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-28028078
ABSTRACT
Whether neuronal inositol-requiring enzyme 1 (Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as "beiging" of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity. At the cellular level, deletion of Ire1α in Pomc neurons elevated hypothalamic endoplasmic reticulum (ER) stress and predisposed Pomc neurons to leptin and insulin resistance. Together, the current studies extend and confirm conclusions that Ire1α-Xbp1s and associated molecular targets link ER stress in arcuate Pomc neurons to aspects of normal energy and glucose homeostasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Proteínas Serina-Treonina Quinases
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Termogênese
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Endorribonucleases
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Metabolismo Energético
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Estresse do Retículo Endoplasmático
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Proteína 1 de Ligação a X-Box
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China