TY - JOUR

T1 - Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice

AU - Kleberg, Karen

AU - Nielsen, Louise Lundeman

AU - Stuhr-Hansen, Nicolai

AU - Nielsen, John

AU - Hansen, Harald Severin

PY - 2014/11

Y1 - 2014/11

N2 - 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 3H-labeled 2-ether analog of triolein (labeled in alkyl group) and compared its disposition with 14C-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 3H uptake. In muscle and adipose tissue, 2-monoacylglycerols are probably further hydrolyzed as seen by an increased 3H/14C 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 3H/14C 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.

AB - 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 3H-labeled 2-ether analog of triolein (labeled in alkyl group) and compared its disposition with 14C-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 3H uptake. In muscle and adipose tissue, 2-monoacylglycerols are probably further hydrolyzed as seen by an increased 3H/14C 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 3H/14C 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.

KW - 2-monoacylglycerol

KW - 2-oleoyl glycerol

KW - 2-oleylglyceryl ether

KW - Adipose tissue

KW - Chemical synthesis

KW - Heart

KW - Lipids

KW - Liver

U2 - 10.1002/biof.1189

DO - 10.1002/biof.1189

M3 - Journal article

AN - SCOPUS:84921023320

VL - 40

SP - 596

EP - 602

JO - BioFactors

JF - BioFactors

SN - 0951-6433

IS - 6

ER -