Methods in Enzymology: Chapter Nineteen - Measurement of ER Stress Response and Inflammation in the Mouse Model of Nonalcoholic Fatty Liver Disease

In eukaryotic cells, the endoplasmic reticulum (ER) is the organelle that is responsible for protein folding and assembly, lipid and sterol biosynthesis, and intracellular calcium storage. Biochemical or pathophysiological stimuli that disrupt protein-folding reaction or increase protein-folding load can cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition called “ER stress”. As an adaptive intracellular stress response initiated from the ER, unfolded protein response (UPR) alleviates the accumulation of unfolded or misfolded proteins in the ER. It has been demonstrated that the UPR is a fundamental intracellular signal transduction response that is critical for health and disease. ER stress and other cellular stress responses, such as inflammation and oxidative stress, are integrated in many pathophysiological processes. Particularly, recent research demonstrated that ER stress and the UPR signaling are critically involved in the initiation and progression of nonalcoholic fatty liver disease (NAFLD). Under metabolic stress conditions, the UPR regulates transcriptional and translational programs that are associated with hepatic steatosis and inflammation, the major characteristics of NAFLD. In this chapter, we summarize reliable methods to quantitatively analyze the UPR and hepatic inflammation in the mouse model of NAFLD.