Corrigendum to: ATF4- and CHOP-dependent induction of FGF21 through endoplasmic reticulum stress (BioMed Research International (2014) 2014 (807874) DOI: 10.1155/2014/807874)

Abstract

Fibroblast growth factor 21 (FGF21) is an important endogenous regulator involved in the regulation of glucose and lipid metabolism. FGF21 expression is strongly induced in animal and human subjects with metabolic diseases, but little is known about themolecularmechanism. Endoplasmic reticulum (ER) plays an essential role in maintenance of metabolic homeostasis and stress-induced ER dysfunction is involved in numerous pathological processes, including type 2 diabetes, obesity, and nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the correlation between the expression of FGF21 and ER stress. We demonstrate that a well-known ER stress inducer, thapsigargin (TG), directly regulates the expression and secretion of FGF21 in a dose- and timedependent manner. We further identify that FGF21 is the target gene of the activating transcription factor 4 (ATF4) and CCAAT enhancer binding protein homologous protein (CHOP). TG-induced transcriptional activation of FGF21 is inhibited inmouse primary hepatocytes isolated fromCHOP knockout mice. In addition, overexpression of ATF4 and CHOP increases FGF21 promoter activities. Furthermore, activation of ER stress significantly increases the mRNA half-life of FGF21. In summary, hepatic FGF21 expression is regulated by ATF4 and CHOP via both transcriptional mechanisms and posttranscriptional mechanisms.