Figure 5.

Integrated response to metabolic stress. A high-fat diet causes metabolic stress associated with increased amounts of saturated free fatty acids, which engage the UPR and stress-activated MAPKs. The UPR includes three different signaling pathways that are initiated by IRE1, PERK, and ATF6. The stress-activated MAPK response is initiated by the MLK group of MAPKKKs and leads to the activation of the JNK and p38 MAPKs. Cross talk between the UPR and stress-activated MAPK signaling leads to an integrated adaptive response.