Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

Theangiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulatingangiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipidmetabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibitinglipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasmatriglycerides (TG) and fatty acids. Subsequently, ANGPTL4 has been shown to be involved in several nonmetabolic andmetabolic conditions, both physiological and pathological, including angiogenesis and vascular permeability, cell differentiation,tumorigenesis, glucose homoeostasis, lipid metabolism, energy homeostasis, wound healing, inflammation, and redox regulation.Thetranscriptional regulation ofANGPTL4 can bemodulated by several transcription factors, including PPAR?, PPAR?/?, PPAR?,and HIF-1?, and nutritional and hormonal conditions. Several studies showed that high levels of ANGPTL4 are associated withpoor prognosis in patients with various solid tumors, suggesting an important role in cancer onset and progression, metastasis,and anoikis resistance. Here, we have discussed the potential role of ANGPTL4 in mediating the cross talk between metabolicsyndromes, such as diabetes and obesity, and cancer through regulation of its expression by PPARs.