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ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.
- Source :
-
Cell reports [Cell Rep] 2017 May 30; Vol. 19 (9), pp. 1794-1806. - Publication Year :
- 2017
-
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.<br /> (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Activating Transcription Factor 6 metabolism
Adipose Tissue drug effects
Adipose Tissue metabolism
Animals
Fatty Acids metabolism
Kidney drug effects
Kidney metabolism
Lipids chemistry
Liver drug effects
Liver pathology
Mice
Mice, Inbred C57BL
Oxidation-Reduction drug effects
Tunicamycin pharmacology
Anorexia metabolism
Anorexia pathology
Endoplasmic Reticulum Stress drug effects
Fatty Liver metabolism
Fatty Liver pathology
Kidney pathology
Lipolysis drug effects
Lipolysis genetics
Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 19
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28564599
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.05.020