Biomaterial Database

Endothelial lipase mediates efficient lipolysis of triglyceride-rich lipoproteins. 2021

Sumeet A Khetarpal, and Cecilia Vitali, and Michael G Levin, and Derek Klarin, and Joseph Park, and Akhil Pampana, and John S Millar, and Takashi Kuwano, and Dhavamani Sugasini, and Papasani V Subbaiah, and Jeffrey T Billheimer, and Pradeep Natarajan, and Daniel J Rader

Departments of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

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.

UI	MeSH Term	Description	Entries
D008049	Lipase	An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3.	Triacylglycerol Lipase,Tributyrinase,Triglyceride Lipase,Acid Lipase,Acid Lipase A,Acid Lipase B,Acid Lipase I,Acid Lipase II,Exolipase,Monoester Lipase,Triacylglycerol Hydrolase,Triglyceridase,Triolean Hydrolase,Hydrolase, Triacylglycerol,Hydrolase, Triolean,Lipase A, Acid,Lipase B, Acid,Lipase I, Acid,Lipase II, Acid,Lipase, Acid,Lipase, Monoester,Lipase, Triglyceride
D008066	Lipolysis	The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.	Lipolyses
D008074	Lipoproteins	Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.	Circulating Lipoproteins,Lipoprotein,Lipoproteins, Circulating
D008081	Liposomes	Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.	Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014280	Triglycerides	An ester formed from GLYCEROL and three fatty acid groups.	Triacylglycerol,Triacylglycerols,Triglyceride
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D059305	Diet, High-Fat	Consumption of excessive DIETARY FATS.	Diet, High Fat,Diets, High Fat,Diets, High-Fat,High Fat Diet,High Fat Diets,High-Fat Diet,High-Fat Diets
D019518	Postprandial Period	The time frame after a meal or FOOD INTAKE.	Postcibal Period,Period, Postcibal,Period, Postprandial,Periods, Postcibal,Periods, Postprandial,Postcibal Periods,Postprandial Periods