ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis
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 suppress...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717306459 |
| _version_ | 1819113331679559680 |
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| author | Diane DeZwaan-McCabe Ryan D. Sheldon Michelle C. Gorecki Deng-Fu Guo Erica R. Gansemer Randal J. Kaufman Kamal Rahmouni Matthew P. Gillum Eric B. Taylor Lynn M. Teesch D. Thomas Rutkowski |
| author_facet | Diane DeZwaan-McCabe Ryan D. Sheldon Michelle C. Gorecki Deng-Fu Guo Erica R. Gansemer Randal J. Kaufman Kamal Rahmouni Matthew P. Gillum Eric B. Taylor Lynn M. Teesch D. Thomas Rutkowski |
| author_sort | Diane DeZwaan-McCabe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T04:27:43Z |
| format | Article |
| id | doaj.art-06fe11739d5947738019a2ca0c310e7e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T04:27:43Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-06fe11739d5947738019a2ca0c310e7e2022-12-21T18:39:07ZengElsevierCell Reports2211-12472017-05-011991794180610.1016/j.celrep.2017.05.020ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney SteatosisDiane DeZwaan-McCabe0Ryan D. Sheldon1Michelle C. Gorecki2Deng-Fu Guo3Erica R. Gansemer4Randal J. Kaufman5Kamal Rahmouni6Matthew P. Gillum7Eric B. Taylor8Lynn M. Teesch9D. Thomas Rutkowski10Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAFraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASection for Metabolic Imaging and Liver Metabolism, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen N, DenmarkFraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USADegenerative Diseases Program, SBP Medical Discovery Institute, La Jolla, CA 92037, USAFraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USASection for Metabolic Imaging and Liver Metabolism, the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen N, DenmarkFraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAHigh Resolution Mass Spectrometry Facility, University of Iowa, Iowa City, IA 52242, USADepartment of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2211124717306459ER stressunfolded protein responsefatty liverfatty kidneyfatty acid oxidationlipolysislipidomics |
| spellingShingle | Diane DeZwaan-McCabe Ryan D. Sheldon Michelle C. Gorecki Deng-Fu Guo Erica R. Gansemer Randal J. Kaufman Kamal Rahmouni Matthew P. Gillum Eric B. Taylor Lynn M. Teesch D. Thomas Rutkowski ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis Cell Reports ER stress unfolded protein response fatty liver fatty kidney fatty acid oxidation lipolysis lipidomics |
| title | ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis |
| title_full | ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis |
| title_fullStr | ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis |
| title_full_unstemmed | ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis |
| title_short | ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis |
| title_sort | er stress inhibits liver fatty acid oxidation while unmitigated stress leads to anorexia induced lipolysis and both liver and kidney steatosis |
| topic | ER stress unfolded protein response fatty liver fatty kidney fatty acid oxidation lipolysis lipidomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717306459 |
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