Peroxisome proliferator-activated receptors as targets to treat metabolic diseases: Focus on the adipose tissue, liver, and pancreas

Figure 4 Schematic illustrates hepatic lipotoxicity caused by obesity. There is an increase in lipolysis, which triggers the intracellular accumulation of fatty acids (FAs) within hepatocytes, resulting in a delay in mitochondrial beta-oxidation followed by an increase in lipogenesis, favoring the deposition of lipid droplets in the hepatic parenchyma, culminating in hepatic steatosis. Concomitantly, there is a reduction in insulin signaling, potentiating inflammation, and endoplasmic reticulum (ER) stress. ER stress is detected by the unfolded protein response-IRE1, PERK, and activating transcription factor 6 (ATF6) in the ER membrane. If it is impossible to reverse the unfolded proteins, ATF4 promotes transcription of the C/element binding protein homologous protein, a transcription factor that induces apoptosis. Made with Biorender (www.biorender.com). TAG: Triacylglycerol; UPR: Unfolded protein response; UPR: Unfolded protein response; PERK: Protein kinase RNA-like ER kinase; ATF: Activating transcription factor 6; IRE6: CHOP: C/EBP homologous protein; NEFAs: Non-esterified fatty acids. Created by BioRender.