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. Author manuscript; available in PMC: 2022 Nov 14.
Published in final edited form as: Semin Liver Dis. 2022 Aug 24;42(3):233–249. doi: 10.1055/s-0042-1755316

Figure 5. ER stress activates three UPR arms.

Figure 5.

Progression of steatosis (NAFLD) to steatohepatitis and fibrosis (NASH) is associated with development of ER stress and activation of the unfolded protein response (UPR) to control hepatic protein and lipid homeostasis. Under physiological conditions, UPR is inactive (due to inhibitory binding of GRP78/BiP to IRE1, PERK, and ATF6) to maintain normal proteostasis in healthy hepatocytes. Upon GRP78 dissociation, all 3 arms of the UPR are activated. In response to chronic injury, all arms of the UPR contribute to NASH and, to different extents, support de novo lipogenesis.