ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.
Cell Rep
; 19(9): 1794-1806, 2017 05 30.
Article
em En
| MEDLINE
| ID: mdl-28564599
ABSTRACT
The unfolded protein response (UPR), induced by endoplasmic reticulum (ER) stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anorexia
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Fígado Gorduroso
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Estresse do Retículo Endoplasmático
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Rim
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Lipólise
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Fígado
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article