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Antioxid Redox Signal. 2011 Jul 15;15(2):505-21. doi: 10.1089/ars.2010.3790. Epub 2011 Apr 26.

Endoplasmic reticulum stress and the unfolded protein response in nonalcoholic fatty liver disease.

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Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado 80523-1571, USA.


The underlying causes of nonalcoholic fatty liver disease (NAFLD) are unclear, although recent evidence has implicated the endoplasmic reticulum (ER) in both the development of steatosis and progression to nonalcoholic steatohepatitis. Disruption of ER homeostasis, often termed "ER stress," has been observed in liver and adipose tissue of humans with NAFLD and/or obesity. Importantly, the signaling pathway activated by disruption of ER homeostasis, the unfolded protein response, has been linked to lipid biosynthesis, insulin action, inflammation, and apoptosis. Therefore, understanding the mechanisms that disrupt ER homeostasis in NAFLD and the role of ER-mediated signaling have become topics of intense investigation. The present review will examine the ER and the unfolded protein response in the context of NAFLD.

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