Endoplasmic reticulum proteostasis in hepatic steatosis

Key Points Increased lipid content in the steatotic liver induces chronic endoplasmic reticulum (ER) stress, mainly via the alteration of Ca 2+ homeostasis Classic ER stress responses such as ER-associated degradation and the unfolded protein response take place to counteract ER stress In the context of the fatty liver, autophagy is unlikely to contribute to the ER stress defence process Rather than alleviating ER stress, aspects of the ER stress responses instead promote hepatocyte lipid accumulation and are, therefore, implicated in the progression of nonalcoholic liver disease.