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

Figure 2 Adipose tissue plasticity and peroxisome proliferator-activated receptor effects. Under an obesogenic diet, the white adipocytes undergo hypertrophy and profound change in adipokine profile release, leading to growing insulin resistance and low-grade inflammation. Conversely, under adequate stimuli [peroxisome proliferator-activated receptors α (PPARα) and dual PPARα/γ], the subcutaneous white adipose tissue can also undergo browning and form beige adipocytes, an intermediate between white and brown adipocytes with lower thermogenic capacity than brown adipocytes but whose presence points to metabolic homeostasis. Finally, the brown adipose tissue, which has the most potent thermogenic capacity, can express a whitened phenotype when exposed to a lipotoxic milieu. Whitening entails decreased vascularization and pro-inflammatory signals characterizing brown adipocyte dysfunction. In contrast, PPARα and dual PPARα/γ treatments counter whitening, increasing thermogenesis through anti-inflammatory and proangiogenic effects. Made with Biorender (www.biorender.com). PPARs: Peroxisome proliferator-activated receptors; WAT: White adipose tissue; BAT: Brown adipose tissue. Created by BioRender.