Selective retention of essential fatty acids: the role of hepatic monoacylglycerol acyltransferase

Abstract

In the suckling rat, chick embryo, and hibernating marmot, fatty acids provide the major source of energy, and despite the high rate of hepatic beta-oxidation, these animals selectively retain long-chain polyunsaturated derivatives of C18:2n-6 and C18:3n-3. To determine whether the hepatic microsomal activity monoacylglycerol acyltransferase (MGAT) (EC 2.3.1.22) could provide a mechanism to selectively acylate monoacylglycerols that contain essential fatty acids, we tested the ability of MGAT activity from each of the three species to acylate sn-2-monoC18:1-, sn-2-monoC18:2-, sn-2-monoC18:3-, and sn-2-monoC20:4-glycerols. Hepatic MGAT activity acylated sn-2-monoC18:3-glycerol and sn-2-monoC18:2-glycerol in preference to sn-2-monoC18:1-glycerol in each of the three different lipolytic animals. MGAT's acyl group specificity could not be explained by invoking differences in membrane fluidity because the apparent affinity for sn-2-monoC20:4-glycerol was not increased. Further, sn-2-monoC18:3-glycerol remained a preferred substrate under assay conditions when both the C18:3 and C18:1 species were present in equal amounts. As would be predicted in the presence of high activity of a selective MGAT, the hepatic glycerolipids from neonatal rats showed increases in dienoic, trienoic, and C22:6 fatty acids and relative decreases in monoenoic, saturated, and C20:4 fatty acids. We hypothesize that, during lipolysis, the reacylation of sn-2-monoacylglycerols by MGAT may provide a mechanism by which essential fatty acids are retained within specific tissues.

MGAT2, a Monoacylglycerol Acyltransferase Expressed in the Small Intestine

“…Both enzymes appeared to prefer unsaturated rather than saturated long chain fatty acyl CoAs. These findings are consistent with the hypothesis that MGAT enzymes preserve unsaturated fatty acids, such as essential fatty acids, by preferentially incorporating them into triacylglycerol for storage (10,11). Alternatively, these findings may reflect limitations in our expression and assay systems.…”

“…Additionally, the K m for monoacylglycerol (ϳ45 M) we observed for hMGAT2 is consistent with previous observations for hepatic MGAT activities in different species (8,15,17). The concentration of monoacylglycerol normally found in cell membranes has been estimated to be much lower than this K m (11), suggesting that the activity of this enzyme depends on increases in monoacylglycerol concentration in the adjacent membrane. Finally, the sigmoidal shape of the curve for hMGAT2 activities with different oleoyl CoA concentrations, which is indicative of an allosteric enzyme regulated by specific effectors or cooperative binding of substrate to multiple sites (10,(22)(23)(24), has been observed in other studies (9,10,25).…”

“…We recently identified a gene encoding an MGAT (MGAT1), which in mice is expressed in the stomach, kidney, white and brown adipose tissues, and liver but not in the intestine (9). The role of MGAT1 in tissues other than the intestine is unknown but may relate to the preservation of polyunsaturated fatty acids in tissues where cycles of triacylglycerol degradation and resynthesis are prominent (10,11). MGAT1 is a member of a gene family that includes DGAT2 and several other homologues that are uncharacterized (12).…”

Identification of a gene encoding MGAT1, a monoacylglycerol acyltransferase

“…It is unclear whether mouse MGAT1 possesses broader substrate specificity than MGAT enzymes in rat tissues, or whether our results are unique to our expression and assay systems. Mouse MGAT1 also preferred unsaturated fatty acyl-CoAs as substrates, consistent with a proposed role of MGAT in preserving essential fatty acids in specific tissues through reesterification cycles (6). The preference of MGAT1 for unsaturated fatty acyl-CoAs contrasts with a reported preference of human intestinal MGAT for saturated fatty acyl-CoAs (19).…”

“…In our study, mouse MGAT1 expressed in insect cells and mammalian cells used both sn-2-monoacylglycerol and sn-1-monoacylglycerol efficiently as substrates. However, in rat tissues, sn-2-monoacylglycerol was the preferred substrate for both small intestine and liver MGAT activity (6,11), although its stereoisomer sn-1(3)-monoacylglycerol can also be used as a substrate (17,18). It is unclear whether mouse MGAT1 possesses broader substrate specificity than MGAT enzymes in rat tissues, or whether our results are unique to our expression and assay systems.…”