Endoplasmic Reticulum Stress and Lipid Metabolism: Mechanisms and Therapeutic Potential

Figure 2

Crosstalk between UPR signalling pathways and lipogenesis. Phosphorylation of eIF2α and activation of the PERK pathway under high-fat diet-induced ER stress conditions allow for enhanced lipogenesis by inducing C/EBPα and decreasing Insig1 protein translation which increases activation of SREBP. However, under severe or prolonged ER stress conditions, CHOP expression may lead to dysregulation of the C/EBPs. Similarly, high-carbohydrate-diet-induced ER stress conditions depend on XBP1 for expression of lipogenic genes and increase of C/EBPα activity, both of which promote lipogenesis. However, severe ER stress conditions, imposed by tunicamycin, lead to XBP1-mediated inhibition of lipogenic gene expression. Furthermore, both XBP1 and ATF6 are important for apolipoprotein B secretion from hepatocytes and activation of fatty acid oxidation pathways (PPARα, PGC1α) under such conditions. These pathways culminate in attenuation of lipogenesis and prevention of fatty liver disease under severe ER stress.