title: The role of ER stress in lipid metabolism and lipotoxicity.
abstract: The endoplasmic reticulum (ER) is a cellular organelle important for regulating calcium homeostasis, lipid metabolism, protein synthesis, and posttranslational modification and trafficking. Numerous environmental, physiological, and pathological insults disturb ER homeostasis, referred to as ER stress, in which a collection of conserved intracellular signaling pathways, termed the unfolded protein response (UPR), are activated to maintain ER function for cell survival. However, excessive and/or prolonged UPR activation leads to initiation of self-destruction through apoptosis. Excessive accumulation of lipids and their intermediate products causes metabolic abnormalities and cell death, called lipotoxicity, in peripheral organs, including the pancreatic islets, liver, muscle, and heart. Because accumulating evidence links chronic ER stress and defects in UPR signaling to lipotoxicity in peripheral tissues, understanding the role of ER stress in cell physiology is a topic under intense investigation. In this review, we highlight recent findings that link ER stress and UPR signaling to the pathogenesis of peripheral organs due to lipotoxicity.
authors.affiliation: Soonchunhyang Institute of Med-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Choongchungnam-do, 31151, Republic of Korea hanjs015@sch.ac.kr rkaufman@sbpdiscovery.org.
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Han
authors.affiliation: Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92307 hanjs015@sch.ac.kr rkaufman@sbpdiscovery.org.
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D056811:Unfolded Protein Response
keywords: cell signaling; diabetes; endoplasmic reticulum; fatty acid; lipids