Sugasini D

References (2)

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

Title : Potential role of hepatic lipase in the accretion of docosahexaenoic acid (DHA) by the brain - Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
Author(s) : Sugasini D , Yang P , Ng D , Khetarpal S , Vitali C , Rader D , Subbaiah PV
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , :159002 , 2021
Abstract : DHA (docosahexaenoic acid) is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA from plasma through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC-DHA). However, the mechanism by which LPC-DHA is generated in the plasma is not known. Our previous studies showed that there are at least three different enzymes - lecithin cholesterol acyltransferase (LCAT), endothelial lipase (EL), and hepatic lipase (HL), which can generate LPC-DHA from sn-2 DHA phosphatidylcholine. Here we determined the relative contributions of these enzymes in the delivery of DHA to the brain by measuring the brain DHA levels in the mice deficient in each of these enzymes. The results show that the brain DHA levels of LCAT-deficient mice or EL-deficient mice were not significantly lower than those of their littermates. However, brain DHA was significantly decreased in HL deficient mice (13.5% of total fatty acids) compared to their littermates (17.1%) (p<0.002), and further decreased to 8.3% of total fatty acids in mice deficient in both HL and EL. These results suggest that HL activity may be the major source for the generation of LPC-DHA in the plasma necessary for transport into the brain, and EL might contribute to this process in the absence of HL.
ESTHER : Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
PubMedSearch : Sugasini_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159002
PubMedID: 34197964