DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass
Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms...
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| Veröffentlicht in: | Scientific reports 2019-03, Vol.9 (1), p.3597-3597, Article 3597 |
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| creator | Gordon, Scott M. Neufeld, Edward B. Yang, Zhihong Pryor, Milton Freeman, Lita A. Fan, Xiao Kullo, Iftikhar J. Biesecker, Leslie G. Remaley, Alan T. |
| description | Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated
Dennd5b
−/−
mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of
Dennd5b
results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common
DENND5B
variant, p.(R52K), is correlated with body mass index. These studies establish an important role for
DENND5B
in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism. |
| doi_str_mv | 10.1038/s41598-019-40296-0 |
| format | Article |
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Dennd5b
−/−
mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of
Dennd5b
results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common
DENND5B
variant, p.(R52K), is correlated with body mass index. These studies establish an important role for
DENND5B
in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-40296-0</identifier><identifier>PMID: 30837651</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>101/28 ; 14/63 ; 45/23 ; 631/45/287/1191 ; 64/60 ; 692/4019/592/75/2099 ; 692/699/2743/393 ; 82/51 ; Absorption ; Aorta ; Arteriosclerosis ; Atherosclerosis ; Biosynthesis ; Body composition ; Body mass index ; Chylomicrons ; Diet ; Disease ; Endoplasmic reticulum ; Enterocytes ; Experiments ; Fatty acids ; Golgi apparatus ; Humanities and Social Sciences ; Intestine ; Laboratory animals ; Lipid metabolism ; Lipids ; Liver ; Metabolism ; multidisciplinary ; Nitrogen ; Obesity ; Oils & fats ; Plasma ; Proteins ; Science ; Science (multidisciplinary) ; Secretion ; Secretory vesicles ; Small intestine</subject><ispartof>Scientific reports, 2019-03, Vol.9 (1), p.3597-3597, Article 3597</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c577t-890f069245bce5de7d798ca4c2f384737e7cd0c46469d59d636c1bec7b2ffb353</citedby><cites>FETCH-LOGICAL-c577t-890f069245bce5de7d798ca4c2f384737e7cd0c46469d59d636c1bec7b2ffb353</cites><orcidid>0000-0002-0197-3811</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401118/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401118/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,41099,42168,51554,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30837651$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gordon, Scott M.</creatorcontrib><creatorcontrib>Neufeld, Edward B.</creatorcontrib><creatorcontrib>Yang, Zhihong</creatorcontrib><creatorcontrib>Pryor, Milton</creatorcontrib><creatorcontrib>Freeman, Lita A.</creatorcontrib><creatorcontrib>Fan, Xiao</creatorcontrib><creatorcontrib>Kullo, Iftikhar J.</creatorcontrib><creatorcontrib>Biesecker, Leslie G.</creatorcontrib><creatorcontrib>Remaley, Alan T.</creatorcontrib><title>DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated
Dennd5b
−/−
mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of
Dennd5b
results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common
DENND5B
variant, p.(R52K), is correlated with body mass index. These studies establish an important role for
DENND5B
in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.</description><subject>101/28</subject><subject>14/63</subject><subject>45/23</subject><subject>631/45/287/1191</subject><subject>64/60</subject><subject>692/4019/592/75/2099</subject><subject>692/699/2743/393</subject><subject>82/51</subject><subject>Absorption</subject><subject>Aorta</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Biosynthesis</subject><subject>Body composition</subject><subject>Body mass index</subject><subject>Chylomicrons</subject><subject>Diet</subject><subject>Disease</subject><subject>Endoplasmic reticulum</subject><subject>Enterocytes</subject><subject>Experiments</subject><subject>Fatty acids</subject><subject>Golgi apparatus</subject><subject>Humanities and Social Sciences</subject><subject>Intestine</subject><subject>Laboratory animals</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Liver</subject><subject>Metabolism</subject><subject>multidisciplinary</subject><subject>Nitrogen</subject><subject>Obesity</subject><subject>Oils & fats</subject><subject>Plasma</subject><subject>Proteins</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Secretion</subject><subject>Secretory vesicles</subject><subject>Small 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acids</topic><topic>Golgi apparatus</topic><topic>Humanities and Social Sciences</topic><topic>Intestine</topic><topic>Laboratory animals</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Liver</topic><topic>Metabolism</topic><topic>multidisciplinary</topic><topic>Nitrogen</topic><topic>Obesity</topic><topic>Oils & fats</topic><topic>Plasma</topic><topic>Proteins</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Secretion</topic><topic>Secretory vesicles</topic><topic>Small intestine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gordon, Scott M.</creatorcontrib><creatorcontrib>Neufeld, Edward B.</creatorcontrib><creatorcontrib>Yang, Zhihong</creatorcontrib><creatorcontrib>Pryor, Milton</creatorcontrib><creatorcontrib>Freeman, Lita A.</creatorcontrib><creatorcontrib>Fan, Xiao</creatorcontrib><creatorcontrib>Kullo, Iftikhar J.</creatorcontrib><creatorcontrib>Biesecker, Leslie 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Rep</addtitle><date>2019-03-05</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>3597</spage><epage>3597</epage><pages>3597-3597</pages><artnum>3597</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated
Dennd5b
−/−
mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of
Dennd5b
results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In humans, two independent exome sequencing studies reveal that a common
DENND5B
variant, p.(R52K), is correlated with body mass index. These studies establish an important role for
DENND5B
in post-Golgi chylomicron secretion and a subsequent influence on body composition and peripheral lipoprotein metabolism.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30837651</pmid><doi>10.1038/s41598-019-40296-0</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-0197-3811</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 101/28 14/63 45/23 631/45/287/1191 64/60 692/4019/592/75/2099 692/699/2743/393 82/51 Absorption Aorta Arteriosclerosis Atherosclerosis Biosynthesis Body composition Body mass index Chylomicrons Diet Disease Endoplasmic reticulum Enterocytes Experiments Fatty acids Golgi apparatus Humanities and Social Sciences Intestine Laboratory animals Lipid metabolism Lipids Liver Metabolism multidisciplinary Nitrogen Obesity Oils & fats Plasma Proteins Science Science (multidisciplinary) Secretion Secretory vesicles Small intestine |
| title | DENND5B Regulates Intestinal Triglyceride Absorption and Body Mass |
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