Angiopoietin-like proteins ANGPTL3 and ANGPTL4 are secreted proteins mainly expressed in liver that have been demonstrated to regulate triglyceride metabolism by inhibiting the lipolysis of triglyceride-rich lipoproteins. ANGPTL3 is structurally similar to angiopoietins, which are vascular endothelial growth factors. The experimental results show that Angptl3 and Angptl4 function to regulate circulating triglyceride levels during different nutritional states and therefore play a role in lipid metabolism during feeding/fasting through differential inhibition of Lipoprotein lipase (LPL). Using deletion mutants of human ANGPTL3, it was demonstrated that the N-terminal domain containing fragment-(17-207) and not the C-terminal fibrinogen-like domain containing fragment-(207-460) increased the plasma triglyceride levels in mice. The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was identified as an adipocytokine up- regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. At the protein level, in human and mouse blood plasma, FIAF was found to be present both as a native protein and in a truncated form. Differentiation of mouse 3T3-L1 adipocytes was associated with the production of truncated FIAF, whereas in human white adipose tissue and SGBS adipocytes, only the native FIAF could be detected. Interestingly, the truncated FIAF was produced by human liver. Experimental data suggest that FIAF is mainly presented in human blood plasma in a truncated form (FIAF-S2), whose level is increased by fenofibrate treatment. Levels of both truncated and native FIAF showed marked inter individual variation but were not associated with body mass index and were not influenced by prolonged semistarvation.