Role of unfolded protein response in lipogenesis

Figure 1 The involvement of the Unfolded Protein Response (UPR) signaling in lipid metabolism. The UPR pathway through inositol-requiring 1α (IRE1α)/XBP1 or activating transcription factor 6 is involved in endoplasmic reticulum (ER) expansion by enhancing phospholipid biosynthesis under ER stress conditions. The IRE1α/XBP1 pathway also regulates lipogenesis by inducing expression of the key enzymes required for triglyceride synthesis under metabolic stress. Additionally, the IRE1α/XBP1 UPR branch can drive C/EBPα expression, facilitating adipogenesis and possibly lipogenesis. The UPR pathway through PERK/eukaryotic translation-initiation factor 2α can stimulate expression of the key lipogenic regulators C/EBPα, C/EBPβ, and PPARγ, promoting lipogenesis under metabolic stress.