Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying
Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor (DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1 (intestine-Dgat1−/−) markedly reduced postprandial plasma TG and retinyl es...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520412532 |
| _version_ | 1818930795835817984 |
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| author | Gene P. Ables Kryscilla Jian Zhang Yang Silke Vogel Antonio Hernandez-Ono Shuiqing Yu Jason J. Yuen Susan Birtles Linda K. Buckett Andrew V. Turnbull Ira J. Goldberg William S. Blaner Li-Shin Huang Henry N. Ginsberg |
| author_facet | Gene P. Ables Kryscilla Jian Zhang Yang Silke Vogel Antonio Hernandez-Ono Shuiqing Yu Jason J. Yuen Susan Birtles Linda K. Buckett Andrew V. Turnbull Ira J. Goldberg William S. Blaner Li-Shin Huang Henry N. Ginsberg |
| author_sort | Gene P. Ables |
| collection | DOAJ |
| description | Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor (DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1 (intestine-Dgat1−/−) markedly reduced postprandial plasma TG and retinyl ester excursions by inhibiting chylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiency of retinol esterification, but it did reduce TG and retinoid accumulation in the small intestine. In contrast, inhibition of microsomal triglyceride transfer protein (MTP) reduced chylomicron secretion after oral fat/retinol loads, but with accumulation of dietary TG and retinoids in the small intestine. Lack of intestinal accumulation of TG and retinoids in DGAT1i-treated or intestine-Dgat1−/− mice resulted, in part, from delayed gastric emptying associated with increased plasma levels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomach through duodenal oil injection nor inhibiting the receptor for GLP-1 normalized postprandial TG or retinyl esters excursions in the absence of DGAT1 activity. In summary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptying and inhibited chylomicron secretion; however, the latter occurred when gastric emptying was normal or when lipid was administered directly into the small intestine. Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition. |
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| format | Article |
| id | doaj.art-ef0ae0cad15247f89a3efeb1b1b8818c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:06:23Z |
| publishDate | 2012-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-ef0ae0cad15247f89a3efeb1b1b8818c2022-12-21T19:54:01ZengElsevierJournal of Lipid Research0022-22752012-11-01531123642379Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptyingGene P. Ables0Kryscilla Jian Zhang Yang1Silke Vogel2Antonio Hernandez-Ono3Shuiqing Yu4Jason J. Yuen5Susan Birtles6Linda K. Buckett7Andrew V. Turnbull8Ira J. Goldberg9William S. Blaner10Li-Shin Huang11Henry N. Ginsberg12Department of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andAstraZeneca R&D, Macclesfield, UKAstraZeneca R&D, Macclesfield, UKAstraZeneca R&D, Macclesfield, UKDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andDepartment of Medicine, Columbia University, New York, NY; andTo whom correspondence should be addressed; Department of Medicine, Columbia University, New York, NY; andAcyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor (DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1 (intestine-Dgat1−/−) markedly reduced postprandial plasma TG and retinyl ester excursions by inhibiting chylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiency of retinol esterification, but it did reduce TG and retinoid accumulation in the small intestine. In contrast, inhibition of microsomal triglyceride transfer protein (MTP) reduced chylomicron secretion after oral fat/retinol loads, but with accumulation of dietary TG and retinoids in the small intestine. Lack of intestinal accumulation of TG and retinoids in DGAT1i-treated or intestine-Dgat1−/− mice resulted, in part, from delayed gastric emptying associated with increased plasma levels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomach through duodenal oil injection nor inhibiting the receptor for GLP-1 normalized postprandial TG or retinyl esters excursions in the absence of DGAT1 activity. In summary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptying and inhibited chylomicron secretion; however, the latter occurred when gastric emptying was normal or when lipid was administered directly into the small intestine. Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition.http://www.sciencedirect.com/science/article/pii/S0022227520412532diacylglycerol acyltransferase inhibitionglucagon-like peptide-1GLP-1 receptor inhibitionlipoproteinsretinol absorption |
| spellingShingle | Gene P. Ables Kryscilla Jian Zhang Yang Silke Vogel Antonio Hernandez-Ono Shuiqing Yu Jason J. Yuen Susan Birtles Linda K. Buckett Andrew V. Turnbull Ira J. Goldberg William S. Blaner Li-Shin Huang Henry N. Ginsberg Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying Journal of Lipid Research diacylglycerol acyltransferase inhibition glucagon-like peptide-1 GLP-1 receptor inhibition lipoproteins retinol absorption |
| title | Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| title_full | Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| title_fullStr | Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| title_full_unstemmed | Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| title_short | Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| title_sort | intestinal dgat1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying |
| topic | diacylglycerol acyltransferase inhibition glucagon-like peptide-1 GLP-1 receptor inhibition lipoproteins retinol absorption |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520412532 |
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