| Hepatic endoplasmic reticulum stress in obesity: Deeper insights into processes, but are they relevant to nonalcoholic steatohepatitis? | |
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MedLine Citation:
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PMID: 22139704 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca over-expression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity. (HEPATOLOGY 2011. |
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Authors:
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Isabelle A Leclercq; Derrick M Van Rooyen; Geoffrey C Farrell |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 54 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-05 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 2261-6 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
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Laboratory of Hepato-gastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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