Glycosylphosphatidylinositol-specific phospholipase D influences triglyceride-rich lipoprotein metabolism.
Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a minor HDL-associated protein. Because many minor HDL-associated proteins exchange between different lipoprotein classes during the postprandial state and are also involved in triglyceride (TG) metabolism, we hypothesized that GPI-PLD may play a role in the metabolism of TG-rich lipoproteins. To test this hypothesis, we examined the distribution of GPI-PLD among lipoprotein classes during a fat tolerance test in C57BL/6 and LDL receptor-deficient (LDLR(-/-)) mice fed either a chow or high-fructose diet. In the fasting state in wild-type mice fed a chow diet, GPI-PLD was only present in HDL, whereas in LDLR(-/-) mice GPI-PLD was present in HDL and intermediate-density lipoproteins (IDL)/LDL. During the fat tolerance test, there was no change in total serum GPI-PLD levels in either model; however, a significant amount of GPI-PLD appeared in both VLDL (0.5-1% of total GPI-PLD) and IDL/LDL (5-10% of total GPI-PLD) in both models. The high-fructose diet increased both fasting and postprandial TG and serum GPI-PLD levels in both strains as well as the amount of GPI-PLD in VLDL. To determine whether GPI-PLD plays a direct role in TG metabolism, we increased liver GPI-PLD expression in C57BL/6 mice by adenovirus-mediated gene transfer, which resulted in a sevenfold increase in serum GPI-PLD levels. This change was associated with an increase in fasting (30%) and postprandial TG (50%) and a twofold reduction in TG-rich lipoprotein catabolism compared with saline or control adenovirus-treated mice. These studies demonstrate that GPI-PLD affects serum TG levels by altering catabolism of TG-rich lipoproteins.
Raikwar
Nandita S
NS
Department of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Cho
Won Kyoo
WK
Bowen
Rosario F
RF
Deeg
Mark A
MA
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005632:Fructose / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional; D010739:Phospholipase D / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism*
D016632:Apolipoprotein A-I; D008074:Lipoproteins; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; D005632:Fructose; D004247:DNA; D010739:Phospholipase D; C065017:glycoprotein phospholipase D