TY - JOUR TI - Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion AU - Rong, Xin AU - Wang, Bo AU - Dunham, Merlow M AU - Hedde, Per Niklas AU - Wong, Jinny S AU - Gratton, Enrico AU - Young, Stephen G AU - Ford, David A AU - Tontonoz, Peter A2 - Walther, Tobias C VL - 4 PY - 2015 DA - 2015/03/25 SP - e06557 C1 - eLife 2015;4:e06557 DO - 10.7554/eLife.06557 UR - https://doi.org/10.7554/eLife.06557 AB - The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride (TG) secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways. KW - phospholipid KW - lipoprotein KW - nuclear receptor JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -