The metabolism of triglyceride-rich lipoproteins revisited: new players, new insight.
Peripheral lipoprotein lipase (LPL)-mediated lipolysis of triglycerides is the first step in chylomicron/VLDL clearance involving heparan sulfate proteoglycans (HSPGs) displayed at the cell surface of the capillaries in adipose tissue, heart and skeletal muscle. The newly generated chylomicron remnant particles are then cleared by the liver, whereas VLDL remnant particles are either further modified, through the action of hepatic lipase (HL) and cholesteryl ester transfer protein (CETP), into LDL particles or alternatively directly cleared by the liver. Two proteins, lipase maturation factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), have been recently identified and have revised our current understanding of LPL maturation and LPL-mediated lipolysis. Moreover, new insights have been gained with respect to hepatic remnant clearance using genetically modified mice targeting the sulfation of HSPGs and even deletion of the most abundant heparan sulfate proteoglycan: syndecan1. In this review, we will provide an overview of novel data on both peripheral TG hydrolysis and hepatic remnant clearance that will improve our knowledge of plasma triglyceride metabolism.
Dallinga-Thie
Geesje M
GM
Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. g.m.dallinga@amc.nl
Franssen
Remco
R
Mooij
Hans L
HL
Visser
Maartje E
ME
Hassing
H Carlijne
HC
Peelman
Frank
F
Kastelein
John J P
JJ
Péterfy
Miklós
M
Nieuwdorp
Max
M
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006801:Humans; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018110:Receptors, Lipoprotein / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*
D002352:Carrier Proteins; D002914:Chylomicrons; C472779:GPI-HBP1 protein, mouse; C523701:GPIHBP1 protein, human; D019812:Heparan Sulfate Proteoglycans; C546366:LMF1 protein, human; C546367:LMF1 protein, mouse; D008074:Lipoproteins; D008565:Membrane Proteins; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C030087:lipoprotein triglyceride; D008071:Lipoprotein Lipase