Shiyu Wang1, Randal J Kaufman. 1. Degenerative Disease Research, Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, La Jolla, California, USA.
Abstract
PURPOSE OF REVIEW: The endoplasmic reticulum (ER) maintains cellular metabolic homeostasis by coordinating protein synthesis, secretion activities, lipid biosynthesis and calcium (Ca²⁺) storage. In this review, we will discuss how altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism and contributes to liver-associated metabolic diseases. RECENT FINDINGS: Perturbed ER functions or accumulation of unfolded protein in the ER leads to the activation of the unfolded protein response (UPR) to protect the cell from ER stress. Recent findings pinpoint the key regulatory role of the UPR in hepatic lipid metabolism and demonstrate the potential causal mechanism of ER stress in metabolic dysregulation including diabetes and obesity. SUMMARY: A wide range of factors can alter the protein-folding environment in the ER of hepatocytes and contribute to dysregulation of hepatic lipid metabolism and liver disease. The UPR constitutes a series of adaptive programs that preserve ER protein-folding environment and maintain hepatic lipid homeostasis. Signaling components of the UPR are emerging as potential targets for intervention and treatment of human liver-associated metabolic diseases.
PURPOSE OF REVIEW: The endoplasmic reticulum (ER) maintains cellular metabolic homeostasis by coordinating protein synthesis, secretion activities, lipid biosynthesis and calcium (Ca²⁺) storage. In this review, we will discuss how altered ER homeostasis contributes to dysregulation of hepatic lipid metabolism and contributes to liver-associated metabolic diseases. RECENT FINDINGS: Perturbed ER functions or accumulation of unfolded protein in the ER leads to the activation of the unfolded protein response (UPR) to protect the cell from ER stress. Recent findings pinpoint the key regulatory role of the UPR in hepatic lipid metabolism and demonstrate the potential causal mechanism of ER stress in metabolic dysregulation including diabetes and obesity. SUMMARY: A wide range of factors can alter the protein-folding environment in the ER of hepatocytes and contribute to dysregulation of hepatic lipid metabolism and liver disease. The UPR constitutes a series of adaptive programs that preserve ER protein-folding environment and maintain hepatic lipid homeostasis. Signaling components of the UPR are emerging as potential targets for intervention and treatment of human liver-associated metabolic diseases.
Authors: Donna M Conlon; Tiffany Thomas; Tatyana Fedotova; Antonio Hernandez-Ono; Gilbert Di Paolo; Robin B Chan; Kelly Ruggles; Sarah Gibeley; Jing Liu; Henry N Ginsberg Journal: J Clin Invest Date: 2016-09-06 Impact factor: 14.808
Authors: Hui Z Mao; Nicole Ehrhardt; Candy Bedoya; Javier A Gomez; Diane DeZwaan-McCabe; Imran N Mungrue; Randal J Kaufman; D Thomas Rutkowski; Miklós Péterfy Journal: J Biol Chem Date: 2014-07-17 Impact factor: 5.157