Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.
Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3950255?pdf=render |
| _version_ | 1818989206176792576 |
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| author | Ping Xie Feng Guo Yinyan Ma Hongling Zhu Freddy Wang Bingzhong Xue Hang Shi Jian Yang Liqing Yu |
| author_facet | Ping Xie Feng Guo Yinyan Ma Hongling Zhu Freddy Wang Bingzhong Xue Hang Shi Jian Yang Liqing Yu |
| author_sort | Ping Xie |
| collection | DOAJ |
| description | Comparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes. |
| first_indexed | 2024-12-20T19:34:47Z |
| format | Article |
| id | doaj.art-1c4f3991a2a44c808db3addcfd697260 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T19:34:47Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1c4f3991a2a44c808db3addcfd6972602022-12-21T19:28:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9165210.1371/journal.pone.0091652Intestinal Cgi-58 deficiency reduces postprandial lipid absorption.Ping XieFeng GuoYinyan MaHongling ZhuFreddy WangBingzhong XueHang ShiJian YangLiqing YuComparative Gene Identification-58 (CGI-58), a lipid droplet (LD)-associated protein, promotes intracellular triglyceride (TG) hydrolysis in vitro. Mutations in human CGI-58 cause TG accumulation in numerous tissues including intestine. Enterocytes are thought not to store TG-rich LDs, but a fatty meal does induce temporary cytosolic accumulation of LDs. Accumulated LDs are eventually cleared out, implying existence of TG hydrolytic machinery in enterocytes. However, identities of proteins responsible for LD-TG hydrolysis remain unknown. Here we report that intestine-specific inactivation of CGI-58 in mice significantly reduces postprandial plasma TG concentrations and intestinal TG hydrolase activity, which is associated with a 4-fold increase in intestinal TG content and large cytosolic LD accumulation in absorptive enterocytes during the fasting state. Intestine-specific CGI-58 knockout mice also display mild yet significant decreases in intestinal fatty acid absorption and oxidation. Surprisingly, inactivation of CGI-58 in intestine significantly raises plasma and intestinal cholesterol, and reduces hepatic cholesterol, without altering intestinal cholesterol absorption and fecal neutral sterol excretion. In conclusion, intestinal CGI-58 is required for efficient postprandial lipoprotein-TG secretion and for maintaining hepatic and plasma lipid homeostasis. Our animal model will serve as a valuable tool to further define how intestinal fat metabolism influences the pathogenesis of metabolic disorders, such as obesity and type 2 diabetes.http://europepmc.org/articles/PMC3950255?pdf=render |
| spellingShingle | Ping Xie Feng Guo Yinyan Ma Hongling Zhu Freddy Wang Bingzhong Xue Hang Shi Jian Yang Liqing Yu Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. PLoS ONE |
| title | Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. |
| title_full | Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. |
| title_fullStr | Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. |
| title_full_unstemmed | Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. |
| title_short | Intestinal Cgi-58 deficiency reduces postprandial lipid absorption. |
| title_sort | intestinal cgi 58 deficiency reduces postprandial lipid absorption |
| url | http://europepmc.org/articles/PMC3950255?pdf=render |
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