Klarin D

References (1)

Title : Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins - Khetarpal_2021_PLoS.Genet_17_e1009802
Author(s) : Khetarpal SA , Vitali C , Levin MG , Klarin D , Park J , Pampana A , Millar JS , Kuwano T , Sugasini D , Subbaiah PV , Billheimer JT , Natarajan P , Rader DJ
Ref : PLoS Genet , 17 :e1009802 , 2021
Abstract : Triglyceride-rich lipoproteins (TRLs) are circulating reservoirs of fatty acids used as vital energy sources for peripheral tissues. Lipoprotein lipase (LPL) is a predominant enzyme mediating triglyceride (TG) lipolysis and TRL clearance to provide fatty acids to tissues in animals. Physiological and human genetic evidence support a primary role for LPL in hydrolyzing TRL TGs. We hypothesized that endothelial lipase (EL), another extracellular lipase that primarily hydrolyzes lipoprotein phospholipids may also contribute to TRL metabolism. To explore this, we studied the impact of genetic EL loss-of-function on TRL metabolism in humans and mice. Humans carrying a loss-of-function missense variant in LIPG, p.Asn396Ser (rs77960347), demonstrated elevated plasma TGs and elevated phospholipids in TRLs, among other lipoprotein classes. Mice with germline EL deficiency challenged with excess dietary TG through refeeding or a high-fat diet exhibited elevated TGs, delayed dietary TRL clearance, and impaired TRL TG lipolysis in vivo that was rescued by EL reconstitution in the liver. Lipidomic analyses of postprandial plasma from high-fat fed Lipg-/- mice demonstrated accumulation of phospholipids and TGs harboring long-chain polyunsaturated fatty acids (PUFAs), known substrates for EL lipolysis. In vitro and in vivo, EL and LPL together promoted greater TG lipolysis than either extracellular lipase alone. Our data positions EL as a key collaborator of LPL to mediate efficient lipolysis of TRLs in humans and mice.
ESTHER : Khetarpal_2021_PLoS.Genet_17_e1009802
PubMedSearch : Khetarpal_2021_PLoS.Genet_17_e1009802
PubMedID: 34543263
Gene_locus related to this paper: mouse-Lipg , human-LIPG