Regulation of metabolic gene expression by the UPR
The UPR regulates metabolic gene expression via several mechanisms. One is direct activation of metabolic gene transcription, such as of Fgf21 and Vldlr by ATF4, or by direct repression of Pparα and Srebf1 by CHOP. Regulation of metabolism can also be indirect, in the sense that at least PDI, which is a target of XBP1, facilitates VLDL biogenesis in addition to its broader role in maintaining the ER oxidative protein folding capacity. Finally, UPR transcription factors can interfere with the activity of metabolic transcriptional regulators, such as HNF4α, FOXO1, or CREB, with consequences for their downstream processes.