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Hepatic endoplasmic reticulum stress in obesity : Deeper insights into processes, but are they relevant to nonalcoholic steatohepatitis?

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Leclercq, Isabelle [UCL] Van Rooyen, Derrick M Farrell, Geoffrey C

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.

Document type Article de périodique (Journal article) – Comment, Journal Article
Access type Accès restreint
Publication date 2011
Language Anglais
Journal information "Hepatology" - Vol. 54, no. 6, p. 2260-2265 (2011)
Peer reviewed yes
Publisher JohnWiley & Sons, Inc. ((United States) Hoboken)
issn 0270-9139
e-issn 1527-3350
Publication status Publié
Affiliations UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie
UCL - (SLuc) Service d'hépato-gastro-entérologie
Links
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Bibliographic reference Leclercq, Isabelle ; Van Rooyen, Derrick M ; Farrell, Geoffrey C. Hepatic endoplasmic reticulum stress in obesity : Deeper insights into processes, but are they relevant to nonalcoholic steatohepatitis?. In: Hepatology, Vol. 54, no. 6, p. 2260-2265 (2011)
Permanent URL http://hdl.handle.net/2078.1/95939