ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis
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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. / DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C; Guo, Deng-Fu; Gansemer, Erica R; Kaufman, Randal J; Rahmouni, Kamal; Gillum, Matthew P; Taylor, Eric B; Teesch, Lynn M; Rutkowski, D Thomas.
In: Cell Reports, Vol. 19, No. 9, 30.05.2017, p. 1794-1806.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis
AU - DeZwaan-McCabe, Diane
AU - Sheldon, Ryan D
AU - Gorecki, Michelle C
AU - Guo, Deng-Fu
AU - Gansemer, Erica R
AU - Kaufman, Randal J
AU - Rahmouni, Kamal
AU - Gillum, Matthew P
AU - Taylor, Eric B
AU - Teesch, Lynn M
AU - Rutkowski, D Thomas
N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2017/5/30
Y1 - 2017/5/30
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1016/j.celrep.2017.05.020
DO - 10.1016/j.celrep.2017.05.020
M3 - Journal article
C2 - 28564599
VL - 19
SP - 1794
EP - 1806
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 9
ER -
ID: 182970044