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Intestinal monoacylglycerol metabolism: regulation and function
Descriptive
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Title
Intestinal monoacylglycerol metabolism: regulation and function
Name
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Chon
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Su-Hyoun
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Su-Hyoun Chon
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author
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Storch
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Judith
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Advisory Committee
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Judith Storch
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chair
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Loredana
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Advisory Committee
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Loredana Quadro
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internal member
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Brasaemle
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Dawn
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Advisory Committee
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Dawn L. Brasaemle
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internal member
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Martin
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Charles
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Advisory Committee
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Charles E. Martin
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outside member
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
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theses
OriginInfo
DateCreated
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2008
DateOther
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2008-10
Language
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English
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electronic
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application/pdf
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text/xml
Extent
xi, 140 pages
Abstract
Sn-2-MG is a major product of dietary lipid digestion, yet its intestinal metabolism has not been investigated beyond its anabolic processing. Recently, a potential for sn-2-MG catabolism in the enterocyte has been proposed. Thus, we examined the regulation of the two known MG metabolizing enzymes, monoacylglycerol acyltransferase (MGAT) and monoacylglycerol lipase (MGL), in mouse small intestine and liver during development and under nutritional modifications. Furthermore, intestinal MGL function was explored by generating transgenic mice (iMGL mice) overexpressing MGL specifically in small intestinal enterocytes.
Dynamic changes in MG metabolism were observed during mouse ontogeny. Hepatic MGL and MGAT expression showed a reciprocal regulation under apparent transcriptional control whereas intestinal MG metabolism did not exhibit any inverse regulation: MGAT2 protein expression and activity were markedly induced during lactation, and then declined. MGL activity increased rapidly at birth and was maintained thereafter. Moreover, discordances in mRNA, protein, and activity levels of intestinal MGAT and MGL were observed, suggesting complex regulatory mechanisms involved in their expression. In addition, intestinal MGL was significantly up-regulated by a high fat diet, indicating its potential role in lipid assimilation.
During high fat feeding, iMGL mice exhibited an obese phenotype secondary to hyperphagia and hypometabolic rate compared to wild type littermates. Dietary lipid absorption and intracellular TG reesterification in iMGL mice intestine were intact. Interestingly, the level of cellular 2-arachidonoyl glycerol (2-AG), one of the endocannabinoids (EC), and cannabinoid receptor 1 (CB1) expression were decreased in iMGL mice intestine. Antagonism of EC signaling is known to reduce appetite and adiposity, and MGL terminates EC signaling by hydrolyzing 2-AG. Here we have a paradox in that intestinal MGL induction caused a phenotype associated with EC system activation rather than termination. While the molecular mechanisms underlying this paradox remain to be elucidated, these studies are the first to indicate that intestinal MG levels significantly affect whole body energy balance via altering appetite and metabolic rate. Thus, we propose a new function for intestinal MG, in which MGL activity is associated with regulatory mechanisms for energy homeostasis, possibly through appetite signaling systems.
Dynamic changes in MG metabolism were observed during mouse ontogeny. Hepatic MGL and MGAT expression showed a reciprocal regulation under apparent transcriptional control whereas intestinal MG metabolism did not exhibit any inverse regulation: MGAT2 protein expression and activity were markedly induced during lactation, and then declined. MGL activity increased rapidly at birth and was maintained thereafter. Moreover, discordances in mRNA, protein, and activity levels of intestinal MGAT and MGL were observed, suggesting complex regulatory mechanisms involved in their expression. In addition, intestinal MGL was significantly up-regulated by a high fat diet, indicating its potential role in lipid assimilation.
During high fat feeding, iMGL mice exhibited an obese phenotype secondary to hyperphagia and hypometabolic rate compared to wild type littermates. Dietary lipid absorption and intracellular TG reesterification in iMGL mice intestine were intact. Interestingly, the level of cellular 2-arachidonoyl glycerol (2-AG), one of the endocannabinoids (EC), and cannabinoid receptor 1 (CB1) expression were decreased in iMGL mice intestine. Antagonism of EC signaling is known to reduce appetite and adiposity, and MGL terminates EC signaling by hydrolyzing 2-AG. Here we have a paradox in that intestinal MGL induction caused a phenotype associated with EC system activation rather than termination. While the molecular mechanisms underlying this paradox remain to be elucidated, these studies are the first to indicate that intestinal MG levels significantly affect whole body energy balance via altering appetite and metabolic rate. Thus, we propose a new function for intestinal MG, in which MGL activity is associated with regulatory mechanisms for energy homeostasis, possibly through appetite signaling systems.
Note
(type = degree)
Ph.D.
Note
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Includes bibliographical references (p. 117-130).
Subject
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Topic
Nutritional Sciences
Subject
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Topic
Phospholipids
Subject
(ID = SUBJ3);
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Topic
Intestinal absorption
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Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17445
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ETD_1097
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Identifier
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doi:10.7282/T3GT5NH6
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ETD doctoral
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The author owns the copyright to this work.
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Copyright protected
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Open
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Suhyoun Chon
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Rutgers University. Graduate School - New Brunswick
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Non-exclusive ETD license
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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