HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 18, 18878-18886, April 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/18/18878    most recent M313272200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cao, J. Articles by Shi, Y. Search for Related Content PubMed PubMed Citation Articles by Cao, J. Articles by Shi, Y. Social Bookmarking                      What's this?

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^*

Jingsong Cao, Eric Hawkins, Joseph Brozinick, Xiaoyu Liu, Hongxing Zhang, Paul Burn, and Yuguang Shi¶

From the Divisions of Endocrine Research and Bioproduct Pharmaceutical Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285

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.

Received for publication, December 4, 2003 , and in revised form, February 4, 2004.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Endocrine Research, DC 0545, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Co., Indianapolis, IN 46285. Tel.: 317-276-6753; Fax: 317-276-9574; E-mail: shi_yuguang{at}lilly.com.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Cheng, J. Iqbal, J. Devenny, C.-H. Chu, L. Chen, J. Dong, R. Seethala, W. J. Keim, A. V. Azzara, R. M. Lawrence, et al. Acylation of Acylglycerols by Acyl Coenzyme A:Diacylglycerol Acyltransferase 1 (DGAT1): FUNCTIONAL IMPORTANCE OF DGAT1 IN THE INTESTINAL FAT ABSORPTION J. Biol. Chem., October 31, 2008; 283(44): 29802 - 29811. [Abstract] [Full Text] [PDF]

				S.-H. Chon, Y. X. Zhou, J. L. Dixon, and J. Storch Intestinal Monoacylglycerol Metabolism: DEVELOPMENTAL AND NUTRITIONAL REGULATION OF MONOACYLGLYCEROL LIPASE AND MONOACYLGLYCEROL ACYLTRANSFERASE J. Biol. Chem., November 16, 2007; 282(46): 33346 - 33357. [Abstract] [Full Text] [PDF]

				C. M. Mansbach II and F. Gorelick Development and Physiological Regulation of Intestinal Lipid Absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G645 - G650. [Abstract] [Full Text] [PDF]

				D. D. Black Development and Physiological Regulation of Intestinal Lipid Absorption. I. Development of intestinal lipid absorption: cellular events in chylomicron assembly and secretion Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G519 - G524. [Abstract] [Full Text] [PDF]

				J. Cao, Y. Liu, J. Lockwood, P. Burn, and Y. Shi A Novel Cardiolipin-remodeling Pathway Revealed by a Gene Encoding an Endoplasmic Reticulum-associated Acyl-CoA:Lysocardiolipin Acyltransferase (ALCAT1) in Mouse J. Biol. Chem., July 23, 2004; 279(30): 31727 - 31734. [Abstract] [Full Text] [PDF]