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Rosalind A. Coleman - One of the best experts on this subject based on the ideXlab platform.
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L-Glutamine and Transforming Growth Factor-α Enhance Recovery of Monoacylglycerol Acyltransferase and Diacylglycerol Acyltransferase Activity in Porcine Postischemic Ileum
Pediatric Research, 1998Co-Authors: Navid Ahdieh, Rosalind A. Coleman, Robert A Argenzio, B. Ganesh Bhat, Anthony T Blikslager, J. Marc RhoadsAbstract:L-Glutamine and Transforming Growth Factor-α Enhance Recovery of Monoacylglycerol Acyltransferase and Diacylglycerol Acyltransferase Activity in Porcine Postischemic Ileum
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Selective retention of essential fatty acids: the role of hepatic Monoacylglycerol acyltransferase.
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1993Co-Authors: Nadia Mostafa, B. G. Bhat, Gregory L. Florant, Rosalind A. ColemanAbstract: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.
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Solubilization and partial purification of neonatally expressed rat hepatic microsomal Monoacylglycerol acyltransferase.
Archives of biochemistry and biophysics, 1993Co-Authors: B. G. Bhat, E.s.g. Bardes, Rosalind A. ColemanAbstract:Rat hepatic microsomal Monoacylglycerol acyltransferase (MGAT) is a developmentally expressed enzyme that catalyzes the formation of sn-1,2-diacylglycerol from sn-2-Monoacylglycerol and fatty acyl-CoA. Treatment of suckling rat liver microsomes with various detergents showed that 0.3% Triton X-100, a nonionic detergent, solubilized a maximum amount of both protein (66%) and MGAT activity (56%). After solubilization with Triton X-100, MGAT was then purified 205-fold by sequential chromatography on QAE-Sephadex, CM-Sepharose (Fast Flow), and hydroxylapatite. Addition of phospholipids to the reaction mixture stimulated the purified enzyme activity more than 1.8-fold. sn-1,2-DiC18: 1-glycerol activated purified MGAT activity. Purified MGAT activity was specific for sn-2-Monoacylglycerol; the activity with rac-1-monoC18:1-glycerol and rac-1- and sn-2-monoC18:1-glycerol ethers was less than 4% of the activity with sn-2-monoC18:1-glycerol. The purified MGAT had an isoelectric point of 9.7. The apparent Km and Vmax values of the purified enzyme for sn-2-monoC18:1-glycerol were 21 microM and 1036 nmol/min/mg, respectively. The apparent Km value for palmitoyl-CoA was 6.5 microM. Purified MGAT activity acylated sn-2-monoC18:2-glycerol and sn-2-monoC18:3-glycerol in preference to sn-2-monoC18:1-glycerol, consistent with a role for the Monoacylglycerol pathway in retaining essential fatty acids.
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Diacylglycerol acyltransferase and Monoacylglycerol acyltransferase from liver and intestine
Methods in Enzymology, 1992Co-Authors: Rosalind A. ColemanAbstract:Publisher Summary The acylation of diacylglycerol catalyzed by the diacylglycerol acyltransferase is the only enzyme reaction unique to triacylglycerol synthesis. This reaction lies at the diacylglycerol branch point of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol synthesis. In most tissues, the major pathway for the biosynthesis of the diacylglycerol substrate proceeds from the acylation of glycerol 3-phosphate. In intestine and liver, however, the Monoacylglycerol pathway provides an alternate route for diacylglycerol synthesis. 2-Monoacylglycerol—produced by the action of gastric and pancreatic lipases on dietary triacylglycerol—enters the intestinal mucosa where Monoacylglycerol acyltransferase plays a major role in resynthesizing triacylglycerol. In the liver of certain species, Monoacylglycerol acyltransferase activity is high during early development; however, neither its specific role in liver nor the source of the Monoacylglycerol substrate is known. Both diacylglycerol acyltransferase and Monoacylglycerol acyltransferase are intrinsic membrane proteins whose active sites face the cytosolic surface of the endoplasmic reticulum.
Harald S. Hansen - One of the best experts on this subject based on the ideXlab platform.
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Sensing of triacylglycerol in the gut: different mechanisms for fatty acids and 2-Monoacylglycerol.
The Journal of physiology, 2015Co-Authors: Karen Kleberg, Johanne Agerlin Windeløv, Anne Jacobsen, Jozélia G. Ferreira, Jens F Rehfeld, Ivan E. De Araujo, Jens J. Holst, Harald S. HansenAbstract:Sensing of dietary triacylglycerol in the proximal small intestine results in physiological, hormonal and behavioural responses. However, the exact physiological pathways linking intestinal fat sensing to food intake and the activation of brain circuits remain to be identified. In this study we examined the role of triacylglycerol digestion for intestinal fat sensing, and compared the effects of the triacylglycerol digestion products, fatty acids and 2-Monoacylglycerol, on behavioural, hormonal and dopaminergic responses in behaving mice. Using an operant task in which mice are trained to self-administer lipid emulsions directly into the stomach, we show that inhibiting triacylglycerol digestion disrupts normal behaviour of self-administration in mice, indicating that fat sensing is conditional to digestion. When administered separately, both digestion products, 2-Monoacylglycerol and fatty acids, were sensed by the mice, and self-administration patterns of fatty acids were affected by the fatty acid chain length. Peripheral plasma concentrations of the gut hormones GLP-1, GIP, PYY, CCK and insulin did not offer an explanation of the differing behavioural effects produced by 2-Monoacylglycerol and fatty acids. However, combined with behavioural responses, striatal dopamine effluxes induced by gut infusions of oleic acid were significantly greater than those produced by equivalent infusions of 2-oleoylglycerol. Our data demonstrate recruitment of different signalling pathways by fatty acids and 2-Monoacylglycerol, and suggest that the structural properties of fat rather than total caloric value determine intestinal sensing and the assignment of reward value to lipids.
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Sensing of triacylglycerol in the gut: different mechanisms for fatty acids and 2‐Monoacylglycerol
The Journal of Physiology, 2015Co-Authors: Karen Kleberg, Johanne Agerlin Windeløv, Anne Jacobsen, Jozélia G. Ferreira, Jens F Rehfeld, Ivan E. De Araujo, Jens J. Holst, Harald S. HansenAbstract:Key points Digestion is required for intestinal sensing of triacylglycerol in this behavioural model. The hydrolysis products of triacylglycerol, fatty acids and 2-Monoacylglycerol, regulate feeding via separate mechanisms. Sensing of long-chain fatty acids, but not of 2-Monoacylglycerol, stimulated central dopaminergic signalling. Fatty acid chain length regulates behavioural responses to fatty acids. Abstract Sensing of dietary triacylglycerol in the proximal small intestine results in physiological, hormonal and behavioural responses. However, the exact physiological pathways linking intestinal fat sensing to food intake and the activation of brain circuits remain to be identified. In this study we examined the role of triacylglycerol digestion for intestinal fat sensing, and compared the effects of the triacylglycerol digestion products, fatty acids and 2-Monoacylglycerol, on behavioural, hormonal and dopaminergic responses in behaving mice. Using an operant task in which mice are trained to self-administer lipid emulsions directly into the stomach, we show that inhibiting triacylglycerol digestion disrupts normal behaviour of self-administration in mice, indicating that fat sensing is conditional to digestion. When administered separately, both digestion products, 2-Monoacylglycerol and fatty acids, were sensed by the mice, and self-administration patterns of fatty acids were affected by the fatty acid chain length. Peripheral plasma concentrations of the gut hormones GLP-1, GIP, PYY, CCK and insulin did not offer an explanation of the differing behavioural effects produced by 2-Monoacylglycerol and fatty acids. However, combined with behavioural responses, striatal dopamine effluxes induced by gut infusions of oleic acid were significantly greater than those produced by equivalent infusions of 2-oleoylglycerol. Our data demonstrate recruitment of different signalling pathways by fatty acids and 2-Monoacylglycerol, and suggest that the structural properties of fat rather than total caloric value determine intestinal sensing and the assignment of reward value to lipids.
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Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-Monoacylglycerol in mice
Biofactors, 2014Co-Authors: Karen Kleberg, Louise Lundeman Nielsen, Nicolai Stuhr-hansen, John Nielsen, Harald S. HansenAbstract: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. © 2014 BioFactors, 40(6):596–602, 2014
Matthew A. Davis - One of the best experts on this subject based on the ideXlab platform.
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α β hydrolase domain 6 accessible Monoacylglycerol controls glucose stimulated insulin secretion
Cell Metabolism, 2014Co-Authors: Shangang Zhao, Yves Mugabo, Marie Line Peyot, Bouchra Taïb, Roxane Lussier, Erik Joly, Jose Antonio Iglesias, Li Xie, Viviane Delghingaroaugusto, Matthew A. DavisAbstract:Summary Glucose metabolism in pancreatic β cells stimulates insulin granule exocytosis, and this process requires generation of a lipid signal. However, the signals involved in lipid amplification of glucose-stimulated insulin secretion (GSIS) are unknown. Here we show that in β cells, glucose stimulates production of lipolysis-derived long-chain saturated Monoacylglycerols, which further increase upon inhibition of the membrane-bound Monoacylglycerol lipase α/β-Hydrolase Domain-6 (ABHD6). ABHD6 expression in β cells is inversely proportional to GSIS. Exogenous Monoacylglycerols stimulate β cell insulin secretion and restore GSIS suppressed by the pan-lipase inhibitor orlistat. Whole-body and β-cell-specific ABHD6-KO mice exhibit enhanced GSIS, and their islets show elevated Monoacylglycerol production and insulin secretion in response to glucose. Inhibition of ABHD6 in diabetic mice restores GSIS and improves glucose tolerance. Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated Monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion.
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α/β-Hydrolase Domain-6-Accessible Monoacylglycerol Controls Glucose-Stimulated Insulin Secretion
Cell Metabolism, 2014Co-Authors: Shangang Zhao, Yves Mugabo, Jose Iglesias, Viviane Delghingaro-augusto, Marie Line Peyot, Bouchra Taïb, Roxane Lussier, Erik Joly, Matthew A. DavisAbstract:Summary Glucose metabolism in pancreatic β cells stimulates insulin granule exocytosis, and this process requires generation of a lipid signal. However, the signals involved in lipid amplification of glucose-stimulated insulin secretion (GSIS) are unknown. Here we show that in β cells, glucose stimulates production of lipolysis-derived long-chain saturated Monoacylglycerols, which further increase upon inhibition of the membrane-bound Monoacylglycerol lipase α/β-Hydrolase Domain-6 (ABHD6). ABHD6 expression in β cells is inversely proportional to GSIS. Exogenous Monoacylglycerols stimulate β cell insulin secretion and restore GSIS suppressed by the pan-lipase inhibitor orlistat. Whole-body and β-cell-specific ABHD6-KO mice exhibit enhanced GSIS, and their islets show elevated Monoacylglycerol production and insulin secretion in response to glucose. Inhibition of ABHD6 in diabetic mice restores GSIS and improves glucose tolerance. Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated Monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion.
Arnis Kuksis - One of the best experts on this subject based on the ideXlab platform.
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Determination of stereochemical configuration of the glycerol moieties in glycoglycerolipids by chiral phase high-performance liquid chromatography.
Lipids, 2001Co-Authors: Yoshinori Takahashi, Yutaka Itabashi, Arnis Kuksis, Minoru SuzukiAbstract:This study reports a simple and sensitive method for determining the absolute configuration of the glycerol moieties in glycoglycerolipids. The method is based on chiral phase high-performance liquid chromatography (HPLC) separations of enantiomeric di- and Monoacylglycerols released from glycosyldi- and Monoacylglycerols, respectively, by periodate oxidation followed by hydrazinolysis. The released di- and Monoacylglycerols were chromatographed as their 3,5-dinitrophenylurethane (3,5-DNPU), and bis(3,5-DNPU) derivatives, respectively. The derivatives were separated on two chiral phases of opposite configuration, (R)-and (S)-1-(1-naphthyl)ethylamine polymers for diacylglycerols and N-(R)-1-(1-naphthyl)ethylaminocarbonyl-(S)-valine and N-(S)-1-(1-naphyl)ethylamino-carbonyl-(R)-valine for Monoacylglycerols. Clear enantiomer separations, which permit the assignment of the glycerol configuration, were achieved for sn-1,2(2,3)-dicyl- and sn-1(3)-Monoacylglycerols generated from linseed oil triacylglycerols by partial Grignard degradation on all the chiral stationary phases employed. Using the method, we have determined the glycerol configuration in the glycosyl-diacylglycerols (monogalactosyl-, digalactosyl-, and sulfquinovo-syldiacylglycerols) and glycosylMonoacylglycerols (monogalactosyl-, digalactosyl-, and sulfoquinovosylMonoacylglycerols) isolated from spinach leaves and the coralline red alga Corallina pilulifera. The results clearly showed that the glycerol moieties in all the glycoglycerolipids examined have S-configuration sn-1,2-diacyl- and sn-1-Monoacylglycerols). The new method demonstrates that chiral phase HPLC provides unambiguous information on the configuration of the glycerol backbone in natural glycosyldi- and Monoacylglycerols, and that the two-step liberation of the free acylglycerols does not compromise glycerol chirality.
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Stereospecificity of Monoacylglycerol and diacylglycerol acyltransferases from rat intestine as determined by chiral phase high-performance liquid chromatography
Lipids, 1993Co-Authors: Richard Lehner, Arnis Kuksis, Yutaka ItabashiAbstract:Using chiral phase high-performance liquid chromatography of diacylglycerols, we have redetermined the ratios of 1,2-/2,3-diacyl-sn-glycerols resulting from acylation of 2-Monoacylglycerols by membrane bound and solubilized triacylglycerol systhetase of rat intestinal mucosa. With 2-oleoyl[-3H]glycerol as the acyl acceptor and oleoyl-CoA as the acyl donor, 97–98% of the diacylglycerol product was 1,2(2,3)-dioleoyl-sn-glycerol, 90% of which was thesn-1,2-and 10% thesn-2,3-enantiomer. The remaining diacylglycerol (less than 3%) was thesn-1,3-isomer. The overall yield of acylation products was 70%, of which 60% were diacylglycerols and 40% triacylglycerols. With 2-oleylglycerol ether as the acyl acceptor and [1-14C]oleoyl-CoA as the acyl donor, 90% of the diradylglycerol was 1-oleoyl-2-oleyl-sn-glycerol and 10% was the 2-oleyl-3-oleoyl-sn-glycerol. The diradylglycerols made up 96% and the triradylglycerols 4% of the radioactive product. With 1-palmitoyl-sn-glycerol as the acyl acceptor and [1-14C]oleoyl-CoA as the acyl donor, the predominant reaction product was 1-palmitoyl-3-oleoyl-sn-glycerol. The 3-palmitoyl-sn-glycerol was not a suitable acyl acceptor. Both 1,2- and 2,3-diacyl-sn-glycerols were substrates for diacylglycerol acyltransferase as neither isomer was favored when 1,2-dioleoyl-rac-[2-3H]glycerol was used as the acyl acceptor. There was a marked decrease in the acylation of the 1(3)-oleoyl-2-oleyl-sn-glycerol to the 1,3-dioleoyl-2-oleyl-sn-glycerol. It is concluded that neither Monoacylglycerol nor diacylglycerol acyltransferase exhibit absolute stereospecificity for acylglycerols as fatty acid acceptors.
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utilization of 2 Monoacylglycerols for phosphatidylcholine biosynthesis in the intestine
Biochimica et Biophysica Acta, 1992Co-Authors: Richard Lehner, Arnis KuksisAbstract:Abstract Conventional preparations of intestinal microsomes were observed to incorporate acetone-solubilized 2-oleoyl-[2-3H]glycerol into dioleoylglycerophosphocholine in the presence of oleoyl CoA and CDP-choline. The apparent Km values for CDP-choline utilization were 77 ± 10 μM in rat and 72 ± 5 μM in hamster. The incorporation ratio of glycerol into triacylglycerols and phosphatidylcholines was 4.5:1 and 25:1 in the rat and hamster, respectively. Endogenous diacylglycerols generated by phospholipase C treatment of microsomes readily equilibrated with the diacylglycerols arising via the Monoacylglycerol pathway as indicated by a dilution of the radioactivity in the triacylglycerol and phosphatidylcholine synthesized from radioactive 2-monooleoylglycerol. These results suggest an alternative pathway for glycerophospholipid formation in the intestinal mucosa during possible inhibition of the phosphatidic acid pathway by dietary 2-Monoacylglycerols. It is concluded that exogenously added Monoacylglycerol can serve as a precursor for microsomal diacyl- and triacylglycerol as well as phosphatidylcholine. The inability to demonstrate comparable Monoacylglycerol utilization in earlier experiments is attributed to the inhibition of choline phosphotransferase by the detergents used to solubilize the acylglycerols.
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Apparent convergence (at 2-Monoacylglycerol level) of phosphatidic acid and 2-Monoacylglycerol pathways of synthesis of chylomicron triacylglycerols
Journal of Lipid Research, 1991Co-Authors: L Y Yang, Arnis KuksisAbstract:Dietary fats are converted into chylomicron triacylglycerols via the 2-Monoacylglycerol and phosphatidic acid pathways of acylglycerol formation. In view of the known positional and fatty acid specificity of the acyltransferases, the triacylglycerol structures resulting from the two pathways would be expected to differ, but this has not been demonstrated. We have performed stereospecific analyses on the chylomicron triacylglycerols from rats fed menhaden oil and the correspond- ing fatty acid alkyl esters, which would be expected to be assimilated via the Monoacylglycerol and the phosphatidic acid pathways, respectively. The results show a remarkable similarity between the two triacylglycerol types in the fatty acid composi- tion of the sn-1 and sn-3 positions, along with marked differences in the composition of the sn-2 positions. The triacylglycerols from rats fed oil retained about 85% of the original fatty acids in the sn-2 position, including a high proportion of the long chain polyunsaturates (e.g., 5-7% 20:5 and 4-5% 22:6). The triacylglycerols from rats fed the alkyl ester contained large amounts of endogenous fatty acids in the sn-2 position (e.g., 18% 16:1, 14% 183, 14% 18:2, and 2.5% 20:4), which approximated the composition of the sn-2 position of the presumed phosphatidic acid intermediates. The sn-1 position contained a much higher proportion of polyunsatured fatty acids (e.g., 12-13% 20:5, 5-6% 22:6) than the sn-2 position (e.g. 2-3% 20:5, 0-0.6% 22:6) of triacylglycerols from rats fed the ester. We conclude that the chylomicron triacylglycerols arising via the 2- Monoacylglycerol and the phosphatidic acid pathways differ mainly in the composition of the fatty acids in the sn-2 position. The similarity in the acids of the sn-1 and sn-3 positions of the chylomicron triacylglycerols from rats fed oil or ester is consis- tent with a hydrolysis of the acylglycerol products of the phosphatidic acid pathway to 2-Monoacylglycerols prior to reconversion to triacylglycerols via the Monoacylglycerol pathway and secretion as chylomicrons.-Yang, L. Y., and A. Kuksis. Apparent convergence (at 2-Monoacylglycerol level) of phosphatidic acid and 2-Monoacylglycerol pathways of synthesis of chylomicron triacylglycerols. J. Lipid Res. 1991. 32: 1173- 1186.
Karen Kleberg - One of the best experts on this subject based on the ideXlab platform.
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Sensing of triacylglycerol in the gut: different mechanisms for fatty acids and 2-Monoacylglycerol.
The Journal of physiology, 2015Co-Authors: Karen Kleberg, Johanne Agerlin Windeløv, Anne Jacobsen, Jozélia G. Ferreira, Jens F Rehfeld, Ivan E. De Araujo, Jens J. Holst, Harald S. HansenAbstract:Sensing of dietary triacylglycerol in the proximal small intestine results in physiological, hormonal and behavioural responses. However, the exact physiological pathways linking intestinal fat sensing to food intake and the activation of brain circuits remain to be identified. In this study we examined the role of triacylglycerol digestion for intestinal fat sensing, and compared the effects of the triacylglycerol digestion products, fatty acids and 2-Monoacylglycerol, on behavioural, hormonal and dopaminergic responses in behaving mice. Using an operant task in which mice are trained to self-administer lipid emulsions directly into the stomach, we show that inhibiting triacylglycerol digestion disrupts normal behaviour of self-administration in mice, indicating that fat sensing is conditional to digestion. When administered separately, both digestion products, 2-Monoacylglycerol and fatty acids, were sensed by the mice, and self-administration patterns of fatty acids were affected by the fatty acid chain length. Peripheral plasma concentrations of the gut hormones GLP-1, GIP, PYY, CCK and insulin did not offer an explanation of the differing behavioural effects produced by 2-Monoacylglycerol and fatty acids. However, combined with behavioural responses, striatal dopamine effluxes induced by gut infusions of oleic acid were significantly greater than those produced by equivalent infusions of 2-oleoylglycerol. Our data demonstrate recruitment of different signalling pathways by fatty acids and 2-Monoacylglycerol, and suggest that the structural properties of fat rather than total caloric value determine intestinal sensing and the assignment of reward value to lipids.
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Sensing of triacylglycerol in the gut: different mechanisms for fatty acids and 2‐Monoacylglycerol
The Journal of Physiology, 2015Co-Authors: Karen Kleberg, Johanne Agerlin Windeløv, Anne Jacobsen, Jozélia G. Ferreira, Jens F Rehfeld, Ivan E. De Araujo, Jens J. Holst, Harald S. HansenAbstract:Key points Digestion is required for intestinal sensing of triacylglycerol in this behavioural model. The hydrolysis products of triacylglycerol, fatty acids and 2-Monoacylglycerol, regulate feeding via separate mechanisms. Sensing of long-chain fatty acids, but not of 2-Monoacylglycerol, stimulated central dopaminergic signalling. Fatty acid chain length regulates behavioural responses to fatty acids. Abstract Sensing of dietary triacylglycerol in the proximal small intestine results in physiological, hormonal and behavioural responses. However, the exact physiological pathways linking intestinal fat sensing to food intake and the activation of brain circuits remain to be identified. In this study we examined the role of triacylglycerol digestion for intestinal fat sensing, and compared the effects of the triacylglycerol digestion products, fatty acids and 2-Monoacylglycerol, on behavioural, hormonal and dopaminergic responses in behaving mice. Using an operant task in which mice are trained to self-administer lipid emulsions directly into the stomach, we show that inhibiting triacylglycerol digestion disrupts normal behaviour of self-administration in mice, indicating that fat sensing is conditional to digestion. When administered separately, both digestion products, 2-Monoacylglycerol and fatty acids, were sensed by the mice, and self-administration patterns of fatty acids were affected by the fatty acid chain length. Peripheral plasma concentrations of the gut hormones GLP-1, GIP, PYY, CCK and insulin did not offer an explanation of the differing behavioural effects produced by 2-Monoacylglycerol and fatty acids. However, combined with behavioural responses, striatal dopamine effluxes induced by gut infusions of oleic acid were significantly greater than those produced by equivalent infusions of 2-oleoylglycerol. Our data demonstrate recruitment of different signalling pathways by fatty acids and 2-Monoacylglycerol, and suggest that the structural properties of fat rather than total caloric value determine intestinal sensing and the assignment of reward value to lipids.
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Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-Monoacylglycerol in mice
Biofactors, 2014Co-Authors: Karen Kleberg, Louise Lundeman Nielsen, Nicolai Stuhr-hansen, John Nielsen, Harald S. HansenAbstract: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. © 2014 BioFactors, 40(6):596–602, 2014
