*Hepatic Lipid Homeostasis in NAFLD DOI: http://dx.doi.org/10.5772/intechopen.108168*

mediated by cell death-inducing DFFA-like effector proteins (CIDE), which lead to the fusion and formation of the large LD [45]. Under fasting or steatosis conditions, CIDEA and CIDEC could be induced to promote LD fusion [48, 49]. In addition to LDs fusion, there exists a potential phenomenon that lipid synthesis directly occurred on the surface of LDs or at newly formed LD-ER membrane bridges, which may also result in LDs expansion. Besides, TG synthesis such as acyl-CoA synthetases as well as the acyltransferases GPAT4 and DGAT2 could expand LD monolayer membrane by inducing excessive TG into the LD core [47, 50]. Once reaching critical concentration, LDs are budded and excreted into the cytoplasm, referred to as a phase separation of the bilayer, and continue to grow the size of LDs. As for LDs budding, *in vitro* studies recently found that several factors could drive the differences in the phospholipid composition between the two leaflets, result in tension asymmetry, which therefore favor budding toward the side with lower monolayer tension [51]. Fat storage-inducing transmembrane protein 2 (FIT2), an integral endoplasmic reticulum membrane protein with lipid-phosphate phosphatase activity, is required for correct budding of nascent LDs, which might promote LDs budding by inducing membrane asymmetries between the ER bilayers. Besides, other factors, including the asymmetric insertion of proteins at the bilayer, the asymmetric acting of lipid-modifying enzymes on leaflets of the bilayer, or an asymmetric refill of newly synthesized phospholipids, may also lead to the asymmetric surface tension of the leaflets.
