Caloric restriction decreases ER stress in liver and adipose tissue in ob/ob mice.
Biochem Biophys Res Commun
; 404(1): 339-44, 2011 Jan 07.
Article
en En
| MEDLINE
| ID: mdl-21134353
Endoplasmic reticulum (ER) stress plays a crucial role in the development of insulin resistance and diabetes. Although caloric restriction (CR) improves obesity-related disorders, the effects of CR on ER stress in obesity remain unknown. To investigate how CR affects ER stress in obesity, ob/ob mice were assigned to either ad libitum (AL) (ob-AL) or CR (ob-CR) feeding (2 g food/day) for 1-4 weeks. The body weight (BW) of ob-CR mice decreased to the level of lean AL-fed littermates (lean-AL) within 2 weeks. BW of lean-AL and ob-CR mice was less than that of ob-AL mice. The ob-CR mice showed improved glucose tolerance and hepatic insulin action compared with ob-AL mice. Levels of ER stress markers such as phosphorylated PKR-like ER kinase (PERK) and eukaryotic translation initiation factor 2α and the mRNA expression of activating transcription factor 4 were significantly higher in the liver and epididymal fat from ob-AL mice compared with lean-AL mice. CR for 2 and 4 weeks significantly reduced all of these markers to less than 35% and 50%, respectively, of the levels in ob-AL mice. CR also significantly reduced the phosphorylation of insulin receptor substrate (IRS)-1 and c-Jun NH(2)-terminal kinase (JNK) in ob/ob mice. The CR-mediated decrease in PERK phosphorylation was similar to that induced by 4-phenyl butyric acid, which reduces ER stress in vivo. In conclusion, CR reduced ER stress and improved hepatic insulin action by suppressing JNK-mediated IRS-1 serine-phosphorylation in ob/ob mice.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Fisiológico
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Tejido Adiposo
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Restricción Calórica
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Retículo Endoplásmico
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Hígado
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Obesidad
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos