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Biochem Res Int. 2012;2012:841362. doi: 10.1155/2012/841362. Epub 2011 Dec 13.

Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential.

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Division of Nephrology, Department of Medicine, McMaster University and St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.


The endoplasmic reticulum (ER) plays a crucial role in protein folding, assembly, and secretion. Disruption of ER homeostasis may lead to accumulation of misfolded or unfolded proteins in the ER lumen, a condition referred to as ER stress. In response to ER stress, a signal transduction pathway known as the unfolded protein response (UPR) is activated. UPR activation allows the cell to cope with an increased protein-folding demand on the ER. Recent studies have shown that ER stress/UPR activation plays a critical role in lipid metabolism and homeostasis. ER-stress-dependent dysregulation of lipid metabolism may lead to dyslipidemia, insulin resistance, cardiovascular disease, type 2 diabetes, and obesity. In this paper, we examine recent findings illustrating the important role ER stress/UPR signalling pathways play in regulation of lipid metabolism, and how they may lead to dysregulation of lipid homeostasis.

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