title: Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice.
abstract: 2-Monoacylglycerols are gaining increasing interest as signaling lipids, beyond endocannabinoids, for example, as ligands for the receptor GPR119 and as mediators of insulin secretion. In the vascular system, they are formed by the action of lipoprotein lipase (LPL); however, their further disposition is unclear. Assuming similar affinity for uptake and incorporation into tissues of 2-oleoylglycerol and 2-oleylglyceryl ether, we have synthesized a (3)H-labeled 2-ether analog of triolein (labeled in alkyl group) and compared its disposition with (14)C-labeled triolein (labeled in glycerol) 20 min after intravenous coadministration in a ratio of 1:1 to mice. We found that peripheral tissues and the liver in particular are able to take up 2-monoacylglycerols as seen from (3)H uptake. In muscle and adipose tissue, 2-monoacylglycerols are probably further hydrolyzed as seen by an increased (3)H/(14)C ratio, whereas in the liver and the heart, data suggest that they are also subjected to re-esterification to triacylglycerol, as seen by an unchanged (3)H/(14)C ratio in the lipid fraction of the tissues. Our findings suggest that LPL-generated 2-monoacylglycerol is likely to be stable in the vascular system and thus have a potential to circulate or at least exert effects in tissues where it may be locally produced.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Kleberg
authors.forename: Louise Lundeman
authors.initials: LL
authors.lastname: Nielsen
authors.forename: Nicolai
authors.initials: N
authors.lastname: Stuhr-Hansen
authors.forename: John
authors.initials: J
authors.lastname: Nielsen
authors.forename: Harald Severin
authors.initials: HS
authors.lastname: Hansen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002250:Carbon Radioisotopes; D004987:Ethers; D005989:Glycerides / Q000378:metabolism; D007275:Injections, Intravenous; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050178:Monoglycerides / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014304:Triolein / Q000008:administration & dosage / Q000378:metabolism; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D004987:Ethers; D005989:Glycerides; D050178:Monoglycerides; D014280:Triglycerides; D014316:Tritium; D014304:Triolein; C505247:2-oleoylglycerol; D008071:Lipoprotein Lipase
keywords: 2-monoacylglycerol; 2-oleoyl glycerol; 2-oleylglyceryl ether; adipose tissue; chemical synthesis; heart; lipids; liver