FIG. 6.

Hypothetical model for the UPR in chronic diseases. Signals that lead to ER stress activate the UPR. The ability of the UPR to alleviate ER stress is linked to the magnitude of the UPR (thin line represents a lower magnitude response; thicker line represents higher magnitude response). The UPR is also linked to multiple cell signaling and metabolic pathways. In chronic diseases like obesity and nonalcoholic fatty liver disease (NAFLD) chronic signals induce ER stress, and perhaps activation of the UPR independently of ER stress. In addition, obesity and/or NAFLD may be characterized by signals that impair the UPR, thus dampening the magnitude of the response and the ability to alleviate ER stress (see text).