A Predominant Role of Acyl-CoA:monoacylglycerol Acyltransferase-2 in Dietary Fat Absorption Implicated by Tissue Distribution, Subcellular Localization, and Up-regulation by High Fat Diet

Abstract

Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinity-purified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption. Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at high levels in human liver, the lower gastrointestinal tract, and the mouse kidney, but the physiological significance of such expression has not yet been studied. Using an affinity-purified antibody, the present study investigated the expression of murine MGAT2 protein along the intestinal tract, determined its subcellular localization, and studied its regulation by diet and in db/db mouse. Results demonstrate a high level of MGAT2 expression in the small intestine in a proximal-to-distal gradient that correlated well with both MGAT enzyme activity and fat absorption pattern. In contrast, MGAT2 protein was not detectable in other sections of the digestive tract, including stomach, cecum, colon, and rectum, or other mouse tissues such as kidney, liver, and adipocytes. Immunohistological studies provided direct evidence that the enzyme is expressed not only in the villi, but also in the crypt regions of the small intestine, which suggests that MGAT2 expression occurs prior to the maturation of enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2-transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by diabetes in the db/db mouse, however, the total intestinal MGAT activity was significantly enhanced. Finally, an up-regulation of both MGAT2 protein expression and MGAT activity was observed in mice fed a high fat diet, implicating a role of MGAT2 in diet-induced obesity. Taken together, our data suggest a predominant role of MGAT2 in dietary fat absorption. In mammals, the small intestine plays a predominant role in the absorption of dietary lipids (mainly triacylglycerol). The absorption of triacylglycerols by the intestinal tract is a complex process that requires several steps, including the hydrolysis of triacylglycerols by pancreatic lipase in the intestinal lumen, the uptake of released 2-monoacylglycerol and fatty acids into enterocytes, and the reconstitution of triacylglycerol in the enterocytes by the monoacylglycerol pathway where 2-monoacylglycerol and fatty acids are utilized to sequentially re-synthesize diacylglycerol and triacylglycerol by acyl-CoA: monoacylglycerol acyltransferase (MGAT) 1The abbreviations used are: MGAT, acyl-CoA:monoacylglycerol acyltransferase; DGAT, acyl-CoA:diacylglycerol acyltransferase; ER, endoplasmic reticulum; PBS, phosphate-buffered saline; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; OLEFT, Otsuka Long-Evans Tokushima Fatty rate; PPARα, peroxisome proliferator-activated receptor α. and acyl-CoA:diacylglycerol acyltransferase (DGAT), respectively. Another pathway involved in the triacylglycerol synthesis is the glycerol 3-phosphate pathway, a de novo pathway that is present in most tissues, including small intestine. The pathway begins with acylation of glycerol 3-phosphate with fatty acyl-CoA producing lysophosphatidic acid, followed sequentially by further acylation and dephosphorylation to yield diacylglycerol (1Lehner R. Kuksis A. Prog. Lipid Res. 1996; 35: 169-201Google Scholar). Both pathways share the final step converting diacylglycerol to triacylglycerol by DGAT. In the small intestinal mucosa the monoacylglycerol pathway contributes to ∼80% of triacylglycerol because of the large amount of 2-monoacylglycerol released from dietary lipids (2Tso P. Crissinger K. Stipanuk M.H. Biochemical and Physiological Aspects of Human Nutrition. W. B. Saunders Co., Philadelphia2000: 125-141Google Scholar, 3Phan C.T. Tso P. Front. Biosci. 2001; 6: D299-D319Google Scholar). The newly formed triacylglycerol is then packaged with other lipids such as cholesterol ester, phospholipids, and protein to form chylomicrons, which are quickly transported to other tissues through the lymphatic system and blood stream (3Phan C.T. Tso P. Front. Biosci. 2001; 6: D299-D319Google Scholar, 4Mansbach 2nd, C.M. Nevin P. J. Lipid Res. 1998; 39: 963-968Google Scholar, 5Westergaard H. Dietschy J.M. J. Clin. Invest. 1976; 58: 97-108Google Scholar). The enzymatic reaction catalyzed by MGAT is an essential step for fat absorption in the small intestine, because triacylglycerol biosynthesis is believed to take place mainly through the monoacylglycerol pathway. High levels of MGAT activity were also found in mammalian white adipose tissue where MGAT is believed to play a role in the storage of triacylglycerol in adipocytes (6Jamdar S.C. Cao W.F. Arch. Biochem. Biophys. 1992; 296: 419-425Google Scholar), where excess storage of triacylglycerol results in obesity. In addition, unlike DGAT, MGAT is not involved in the glycerol 3-phosphate pathway that is present in most tissues. These differential features suggest that MGAT may present a better target for intervening the dietary absorption as a means of treating obesity. Because of the importance of MGAT in fat absorption, considerable studies have been conducted to elucidate its molecular and enzymatic features (7Manganaro F. Kuksis A. Can. J. Biochem. Cell Biol. 1985; 63: 341-347Google Scholar, 8Lehner R. Kuksis A. J. Biol. Chem. 1995; 270: 13630-13636Google Scholar, 9Bhat B.G. Bardes E.S. Coleman R.A. Arch Biochem. Biophys. 1993; 300: 663-669Google Scholar). Facilitated by the recent advances in genomics and bioinformatics, three mammalian MGAT enzymes, designated MGAT1, MGAT2, and MGAT3, have been identified recently (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, 11Cheng D. Nelson T.C. Chen J. Walker S.G. Wardwell-Swanson J. Meegalla R. Taub R. Billheimer J.T. Ramaker M. Feder J.N. J. Biol. Chem. 2003; 278: 13611-13614Google Scholar, 12Yen C.L. Farese Jr., R.V. J. Biol. Chem. 2003; 278: 18532-18537Google Scholar, C.L. P. Farese Jr., R.V. A. Scholar). MGAT1 were mainly in the and and at lower levels in adipose tissue and liver, but were in the small intestine where the level of MGAT activity was C.L. P. Farese Jr., R.V. A. Scholar). The identified MGAT2 and MGAT3 are expressed in small intestine and for the high MGAT activity in tissue (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, 11Cheng D. Nelson T.C. Chen J. Walker S.G. Wardwell-Swanson J. Meegalla R. Taub R. Billheimer J.T. Ramaker M. Feder J.N. J. Biol. Chem. 2003; 278: 13611-13614Google Scholar). of mouse MGAT2 expressed in mammalian and system were further with to for and Cao J. Burn P. Shi Y. J. 2003; Scholar, J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: Scholar). the of MGAT in small intestine were investigated (7Manganaro F. Kuksis A. Can. J. Biochem. Cell Biol. 1985; 63: 341-347Google Scholar, J.M. F. C.M. Biophys. Scholar, F. J.M. Biophys. Scholar, R. Kuksis A. J. Biol. Chem. 1993; Scholar), the in of the intestinal MGAT has not been because of the of identified or MGAT activity has been to be by a of and physiological including and diabetes R.A. J. Biol. Chem. Scholar, B.G. Coleman R.A. Biophys. 1993; Scholar, S.C. Coleman R.A. J. 1993; Scholar, Y. K. Res. Clin. Scholar). diabetes was to MGAT activity in and in Otsuka Long-Evans Tokushima Fatty Y. K. Res. Clin. Scholar). to the of a MGAT at the of the observed in MGAT were to in both mRNA and protein In the present the expression and of the mouse MGAT2 in the intestinal tract and other tissues by an affinity-purified to The data that both MGAT2 mRNA and protein were expressed along the of the small intestine with the levels in and levels in the of which correlated well with the MGAT enzyme and a the and of the small intestine, and the enzyme was localized in the ER in both COS-7 and Caco-2 with further investigated MGAT expression and enzyme in mice fed a high fat diet and in db/db mouse, a of diabetes by of receptor and with the acid, and were from was from other and used in study were from a to of mouse MGAT2 was was to the to in to as a of was further an by the to of the were at or at for and or db/db were from were in an with and to and for at mice were into was fed protein fat and and the other was high fat diet protein fat and The mice were fed the for were with then with of The small intestine was with PBS, into and at for for or total protein The most from the was designated as the the most to the was the of the small and and and colon, rectum, liver, kidney, and and adipose were also for of used in study were in with and to of of D. Scholar). mouse tissues were in of with a of the were in or for or enzymatic The protein in were determined by a to the of MGAT2 in mammalian expression a mouse MGAT2 was as (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: Scholar). subcellular human MGAT2 was with a COS-7 and Caco-2 were the by and with with or an MGAT2 as (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar). were with in for studies or in phosphate-buffered by and to and enzymatic or in for In for MGAT activity was determined by the of into diacylglycerol with and as (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: Scholar). the reaction of of in and protein from small intestine The reaction was conducted at for in a total of were and as (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: Scholar). was from tissues by to the of total was in a and to a The was with from of mouse MGAT2 a was in at followed by three at in and were with to and with glyceraldehyde-3-phosphate as an The were to a to the a which were the from tissues or COS-7 was by in of the protein was or by and to The was for at in to The were then with primary antibody, in the at the was with for at the were for and to for to or a for mice were by with in the small intestine was and to and were at in the sections were with a with the for with PBS, and at to the sections were with with for to the of the The sections were also with in for to the The in of was an system with for the sections were with in for to were with the primary at with for the sections were with for three with as and with for three with PBS, sections were with a and for to the The sections were then with sequentially by and in a and observed by was conducted as for of primary with further the MGAT2 from a was by the affinity-purified with the used to the prior to to the were and a were in the with for at to the were with and with in with for the were with in for to were with mouse or for at with three for the were with and for with PBS, and in a the for of the The were also with to are as The were by of MGAT2 mRNA the in intestinal distribution of mouse MGAT2 mRNA was by with as in a from mouse and the from mice MGAT2 mRNA was expressed in of the small intestine. The expression in to was lower that in sections and to the level of expression was found in the of a proximal-to-distal gradient from was in MGAT2 mRNA expression along the small intestine that the expression of MGAT2 mRNA was only to the small intestine the intestinal tract, because the were in cecum, colon, and of MGAT2 in further the expression and of MGAT2 in several present in to the with that to the of of protein a high The was for by of in COS-7 with MGAT2 with as a were by and by The a at molecular of from cells, which was in and was not by from the The by the also well with the molecular of from the of the mouse MGAT2 as well as the protein in J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: Scholar), a of such as These features the of the antibody, which was further by an and used the The expression of along the small intestinal tract was by the affinity-purified in a the a with a molecular of which is with was observed in MGAT2-transfected COS-7 and is believed to be the MGAT2 enzyme in the small intestine. of MGAT2 protein levels in from three mice is in was the in the mRNA expression MGAT2 protein was expressed the small intestine. gradient from the regions to the regions was with the levels in The expression levels of MGAT2 in the most of the small intestine were at lower study was to the protein expression of MGAT2 in other digestive tissues or in tissues where MGAT2 were (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar). in the protein expression of MGAT2 in liver, kidney, stomach, cecum, colon, and was not our in with high expression of MGAT2 in small intestine and MGAT2-transfected COS-7 a was in tissues lower that MGAT2 protein levels in tissues were lower that in the small intestine, high levels of MGAT2 were observed in of tissues such as and adipose (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar). of and of MGAT2 the a MGAT2 expression and MGAT activity along the small intestine, MGAT activity in from intestinal of in a of the of from a mouse, and the data from three the MGAT activity was observed in to the the activity was which a to a distribution of MGAT activity along the small intestine is with the expression of both MGAT2 mRNA and protein as in and of the levels of and enzyme activity a the three for MGAT2 along the small intestinal tract as in a role for MGAT2 in dietary fat absorption. In of MGAT2 by were to the tissue distribution of MGAT2 in the small intestine. studies were from of mouse small intestine by an which a with was in a the and and where the enterocytes are was also found in the lower crypt regions and where and are believed to The were in of the small intestine. The in to and is was found the villi, at an site or the indicating MGAT2 of the enterocytes. a of the not The of the was further by the of the in a where the primary was with an amount of the used to the These provided direct evidence that MGAT2 is localized of enterocytes along both the and the crypt regions in the small intestine. of the subcellular of MGAT2, studies in COS-7 as well as in Caco-2 with a form of human were for with or with for the and a ER protein that as an ER H. J. Cell Biol. Scholar). were also with to expressed in both a and was not with of and as by the well and in the of and was with the ER of and as by the in the of and The that MGAT2 well with the ER in both COS-7 and Caco-2 suggests that the subcellular distribution of MGAT2 to ER was not the from Caco-2 the in because Caco-2 were from the intestinal tract and the in to that of intestinal enterocytes J. J. Biol. Chem. 1993; Scholar), the expression of the three is by in the not for the was observed in with with or mouse and not of the of MGAT2 and MGAT in db/db as with from the in physiological or are to MGAT activity R.A. J. Biol. Chem. Scholar, B.G. Coleman R.A. Biophys. 1993; Scholar, S.C. Coleman R.A. J. 1993; Scholar). MGAT activity was observed in and a in fat absorption as a of a role of MGAT2 in diabetes and the level of MGAT2 expression and enzyme activity in the small intestine of db/db a of diabetes and by a of the receptor of the db/db mice were and The and of the db/db mice used in the present studies were and which are significantly the mice and The expression of MGAT2 protein and MGAT enzymatic activity in the small intestine of db/db mice were by and enzyme and with from as of protein the levels of MGAT2 protein expression in the of small intestine were for mice and for db/db mice respectively. The MGAT in were for mice and for db/db mice of respectively. is in MGAT2 expression or MGAT in db/db mice as with that from mice as of intestinal the total intestinal MGAT activity was significantly in the db/db mice that from the to a of the small intestine in the db/db mice by of MGAT2 and MGAT in the High of the role of MGAT2 in intestinal fat absorption, the expression of MGAT2 and MGAT along the small intestine be by a high fat The mice were with diet or high fat diet for as the expression levels of the MGAT2 protein in of the and the small intestine from mice fed diet or high fat the levels from the in which were and with MGAT2 were with of The of MGAT2 expression were expressed as of the of mice The data that the expression levels of the intestinal MGAT2 protein was significantly in mice fed high fat diet in with MGAT2 expression of high fat mice was in with a observed in the lower intestinal In with the MGAT protein MGAT enzyme activity was also significantly in mice fed the high fat diet in with the studies that MGAT2 mRNA is expressed in small intestine both in human and mouse, the in tissue and distribution (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, Cao J. Burn P. Shi Y. J. 2003; Scholar). The present studies direct evidence that not only mRNA but also MGAT2 protein is most expressed in small intestine, a proximal-to-distal gradient that well with MGAT enzyme is with that MGAT activity is most in and in D. J. Scholar, S.C. Cao W.F. Biophys. 1995; Scholar). the distribution of MGAT2 and activity well with that of dietary fat absorption along the small intestinal tract (3Phan C.T. Tso P. Front. Biosci. 2001; 6: D299-D319Google Scholar, Scholar, Scholar, J. Clin. Scholar). was that absorption of dietary fat in the small intestinal tract is by a of or of Scholar, Scholar, J. Clin. Scholar), our data suggest that lower MGAT2 expression and activity in regions of the small intestine also to In to its high protein expression in small intestine, protein was not in the lower intestinal tract, including cecum, colon, and The distribution of MGAT is also with that of and mRNA Jr., Farese Jr., R.V. J. Biol. Chem. Scholar), the that of triacylglycerol is an process dietary fat absorption. In addition to its predominant expression in the gastrointestinal tract, MGAT2 were also in kidney, liver, and adipocytes (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, Cao J. Burn P. Shi Y. J. 2003; Scholar), that the enzyme also be involved in fat storage in tissues. In an to a role of MGAT in tissues, protein expression of MGAT2 an results that the level of expression is lower in tissues that in the small intestine, including mouse where a high level of was (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar), a The results also a predominant role of MGAT2 in dietary fat absorption. The data are with our of a of MGAT activity in human liver, a tissue that high levels of MGAT2 mRNA Cao J. Burn P. Shi Y. J. 2003; Scholar). The of the of MGAT2 expression but to of MGAT2 in tissues or a of newly MGAT2 The has been in the expression of as well as Clin. Scholar, J. Biol. Chem. Scholar, Biol. 1985; Scholar, M. J. Biol. Chem. Scholar, C.M. Arch. Biochem. Biophys. 1993; Scholar), which are also involved in Another intestinal MGAT designated MGAT3, was recently identified by D. Nelson T.C. Chen J. Walker S.G. Wardwell-Swanson J. Meegalla R. Taub R. Billheimer J.T. Ramaker M. Feder J.N. J. Biol. Chem. 2003; 278: 13611-13614Google Scholar). that the expression of human MGAT3 is also to the tract with the mRNA level found in the the of the MGAT3 to be in MGAT2 and MGAT3 may play a or role to or dietary fat absorption. the of MGAT may be involved in the synthesis of diacylglycerol in tissues, such as kidney, and (10Cao J. Lockwood J. Burn P. Shi Y. J. Biol. Chem. 2003; 278: 13860-13866Google Scholar, 12Yen C.L. Farese Jr., R.V. J. Biol. Chem. 2003; 278: 18532-18537Google Scholar, C.L. P. Farese Jr., R.V. A. Scholar, Cao J. Burn P. Shi Y. J. 2003; Scholar). are pathways for triacylglycerol the glycerol 3-phosphate pathway and the MGAT pathway (1Lehner R. Kuksis A. Prog. Lipid Res. 1996; 35: 169-201Google Scholar). The glycerol 3-phosphate pathway is believed to be a de novo pathway that is present in most tissues and plays a role in triacylglycerol storage and The activity of pathway is determined by the of and fatty In intestinal mucosa absorption the monoacylglycerol pathway contributes to ∼80% of triacylglycerols into (2Tso P. Crissinger K. Stipanuk M.H. Biochemical and Physiological Aspects of Human Nutrition. W. B. Saunders Co., Philadelphia2000: 125-141Google Scholar, 3Phan C.T. Tso P. Front. Biosci. 2001; 6: D299-D319Google Scholar), synthesis in is believed to the acylation of glycerol because MGAT activity has been in or human Cao J. Burn P. Shi Y. J. 2003; Scholar, B.G. Coleman R.A. J. 1993; Scholar). with the of the in both both and are expressed Farese Jr., R.V. A. 1998; Scholar, P. B. Farese Jr., R.V. J. Biol. Chem. 2001; Scholar). In contrast, the three MGAT are expressed in the gastrointestinal of MGAT2 protein expression in tissues other the small intestine in with tissue distribution of the other MGAT enzymes, further the that MGAT are to absorption both are involved in the of MGAT and may significantly in physiological that MGAT2 may present a better target for intervening dietary fat absorption as a means to obesity. The study for the to the in of MGAT2 protein in small intestine and provided direct evidence that the enzyme the enterocytes. results in addition to enterocytes along and the crypt also is believed that the is with enterocytes and is by crypt and into the of the J. 1995; Scholar, of the and of Lipid Scholar). In to a that MGAT is found to be from R. Biophys. 1976; Scholar), the of in crypt regions the by and Kuksis Kuksis A. Biophys. that the crypt MGAT MGAT2 expression and activity to be prior to the into enterocytes. MGAT activity was believed to in the of both and small intestine R.A. Biophys. 1985; Scholar, Biophys. Scholar), which was by of MGAT in D. Nelson T.C. Chen J. Walker S.G. Wardwell-Swanson J. Meegalla R. Taub R. Billheimer J.T. Ramaker M. Feder J.N. J. Biol. Chem. 2003; 278: 13611-13614Google Scholar, 12Yen C.L. Farese Jr., R.V. J. Biol. Chem. 2003; 278: 18532-18537Google Scholar, C.L. P. Farese Jr., R.V. A. Scholar). Using the for ER and the present study provided direct evidence that the MGAT2 enzyme is localized in the ER, but not in the a distribution is not because were with MGAT2 expressed in COS-7 as well as in Caco-2 cells, a from the in levels of and and is of the features with diabetes and obesity. In addition, MGAT activity has been observed in of In activity B.G. Coleman R.A. Biophys. 1993; Scholar). In MGAT activity in small intestine was that in Y. K. Res. Clin. Scholar). in the of involved in the monoacylglycerol pathway were of glycerol 3-phosphate pathway significantly in to S.C. Cao W.F. Biophys. 1995; Scholar). In in study diabetes in db/db mice affected MGAT2 expression levels MGAT activity in small intestine expressed as because the small of db/db mice are that of the the total MGAT2 enzyme and activity in the small of db/db mice were significantly the observed in db/db was detectable MGAT2 protein and only MGAT activity observed not that the MGAT pathway in the is involved in the observed in db/db The the of MGAT2 by high fat diet be that of PPARα, which is to be expressed in small intestine A. H. J. Biochem. Biophys. Res. 1996; Scholar), may play a role in the process of up-regulation of MGAT2 in to high fat was to the expression of several involved in fatty in small intestine, such as fatty and fatty J. F. J. A. F. A. H. B. D. 2003; Scholar). of the MGAT2 may be to by or other of in to levels of fatty acids in the mucosa to the of dietary absorption. studies are also to a role of MGAT2 in human such as a of MGAT2 with of human as with P. P. B. A. K. Res. 2003; Scholar, Farese Jr., R.V. Clin. Scholar). and of mice in MGAT2 expression a role for MGAT2 in dietary fat absorption, as well as in diet-induced obesity. of a diet is believed to be of the to the in the The small intestine is to large in the amount and of dietary and enterocytes to an absorption M. R. Biophys. have that fed a high fat diet an in the of the and a in the the crypt to a high fat diet also in in fat Chen M. R.A. C.M. 2003; Scholar), the and of pancreatic as well as the of enterocytes to J. Scholar, R.A. J. 1996; 270: Scholar, J. Lipid Res. Scholar). fed a high fat diet a and to M. J. Scholar, R. J. 2001; Scholar). In for the that the intestinal MGAT2 expression and were significantly in to a high fat diet, which may in for the in the enterocytes to dietary fat absorption. the results suggest that MGAT may play a role in the diet-induced obesity. Taken together, our data tissue subcellular localization, and regulation by high fat diet of the MGAT2 protein suggest a predominant role of the enzyme in dietary fat absorption. for studies and and Lockwood for the