Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression
Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we i...
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| Veröffentlicht in: | Molecular biology of the cell 2010-06, Vol.21 (12), p.1991-2000 |
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| container_issue | 12 |
| container_start_page | 1991 |
| container_title | Molecular biology of the cell |
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| creator | Wang, Huajin Wei, Enhui Quiroga, Ariel D Sun, Xuejin Touret, Nicolas Lehner, Richard |
| description | Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes. |
| doi_str_mv | 10.1091/mbc.e09-05-0364 |
| format | Article |
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Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes.</description><identifier>ISSN: 1059-1524</identifier><identifier>ISSN: 1939-4586</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.e09-05-0364</identifier><identifier>PMID: 20410140</identifier><language>eng</language><publisher>United States: The American Society for Cell Biology</publisher><subject>Animals ; Cytosol - drug effects ; Cytosol - metabolism ; Diglycerides - metabolism ; Endoplasmic Reticulum - drug effects ; Endoplasmic Reticulum - enzymology ; Female ; Gene Deletion ; Hepatocytes - drug effects ; Hepatocytes - enzymology ; Lipase - deficiency ; Lipase - metabolism ; Lipid Metabolism - drug effects ; Mice ; Microsomes - drug effects ; Microsomes - metabolism ; Oleic Acid - pharmacology ; Phospholipids - metabolism ; Protein Transport - drug effects ; Triglycerides - metabolism</subject><ispartof>Molecular biology of the cell, 2010-06, Vol.21 (12), p.1991-2000</ispartof><rights>2010 by The American Society for Cell Biology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-15b54c8fe39878dc211c33f5e43a70e086df809dae4a640043c35137015e016c3</citedby><cites>FETCH-LOGICAL-c504t-15b54c8fe39878dc211c33f5e43a70e086df809dae4a640043c35137015e016c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883943/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883943/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20410140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Parton, Robert G.</contributor><creatorcontrib>Wang, Huajin</creatorcontrib><creatorcontrib>Wei, Enhui</creatorcontrib><creatorcontrib>Quiroga, Ariel D</creatorcontrib><creatorcontrib>Sun, Xuejin</creatorcontrib><creatorcontrib>Touret, Nicolas</creatorcontrib><creatorcontrib>Lehner, Richard</creatorcontrib><title>Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><description>Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes.</description><subject>Animals</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - metabolism</subject><subject>Diglycerides - metabolism</subject><subject>Endoplasmic Reticulum - drug effects</subject><subject>Endoplasmic Reticulum - enzymology</subject><subject>Female</subject><subject>Gene Deletion</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - enzymology</subject><subject>Lipase - deficiency</subject><subject>Lipase - metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Mice</subject><subject>Microsomes - drug effects</subject><subject>Microsomes - metabolism</subject><subject>Oleic Acid - pharmacology</subject><subject>Phospholipids - metabolism</subject><subject>Protein Transport - drug effects</subject><subject>Triglycerides - metabolism</subject><issn>1059-1524</issn><issn>1939-4586</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1P3DAQxa2qqHz13BvyrafAOLYT-1IJIQqVkLjAhYvldSa7BidO7Sxq_vt6xYLa08xo3rx50o-QbwzOGWh2MazcOYKuQFbAG_GJHDHNdSWkaj6XHqSumKzFITnO-RmACdG0X8hhDYKVAY7I02WYMWFHg598R7sUp4Az7ZbRDt5l6ke6wcnO0S0zZhqse_Hjms7JW7eEdVgcphjoZimXwWak-GdKmLOP4yk56G3I-HVfT8jjz-uHq9vq7v7m19XlXeUkiLnkW0nhVI9cq1Z1rmbMcd5LFNy2gKCarlegO4vCNgJAcMcl4y0wicAax0_IjzffabsasHM4zskGMyU_2LSYaL35fzP6jVnHV1MrxbXgxeD73iDF31vMsxl8dhiCHTFus2k5r3WrhSrKizelSzHnhP3HFwZmB8QUIKYAMSDNDki5OPs33If-nQD_C_CYido</recordid><startdate>20100615</startdate><enddate>20100615</enddate><creator>Wang, Huajin</creator><creator>Wei, Enhui</creator><creator>Quiroga, Ariel D</creator><creator>Sun, Xuejin</creator><creator>Touret, Nicolas</creator><creator>Lehner, Richard</creator><general>The American Society for Cell Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100615</creationdate><title>Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression</title><author>Wang, Huajin ; Wei, Enhui ; Quiroga, Ariel D ; Sun, Xuejin ; Touret, Nicolas ; Lehner, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-15b54c8fe39878dc211c33f5e43a70e086df809dae4a640043c35137015e016c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - metabolism</topic><topic>Diglycerides - metabolism</topic><topic>Endoplasmic Reticulum - drug effects</topic><topic>Endoplasmic Reticulum - enzymology</topic><topic>Female</topic><topic>Gene Deletion</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Lipase - deficiency</topic><topic>Lipase - metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Mice</topic><topic>Microsomes - drug effects</topic><topic>Microsomes - metabolism</topic><topic>Oleic Acid - pharmacology</topic><topic>Phospholipids - metabolism</topic><topic>Protein Transport - drug effects</topic><topic>Triglycerides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Huajin</creatorcontrib><creatorcontrib>Wei, Enhui</creatorcontrib><creatorcontrib>Quiroga, Ariel D</creatorcontrib><creatorcontrib>Sun, Xuejin</creatorcontrib><creatorcontrib>Touret, Nicolas</creatorcontrib><creatorcontrib>Lehner, Richard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Huajin</au><au>Wei, Enhui</au><au>Quiroga, Ariel D</au><au>Sun, Xuejin</au><au>Touret, Nicolas</au><au>Lehner, Richard</au><au>Parton, Robert G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2010-06-15</date><risdate>2010</risdate><volume>21</volume><issue>12</issue><spage>1991</spage><epage>2000</epage><pages>1991-2000</pages><issn>1059-1524</issn><issn>1939-4586</issn><eissn>1939-4586</eissn><abstract>Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes.</abstract><cop>United States</cop><pub>The American Society for Cell Biology</pub><pmid>20410140</pmid><doi>10.1091/mbc.e09-05-0364</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cytosol - drug effects Cytosol - metabolism Diglycerides - metabolism Endoplasmic Reticulum - drug effects Endoplasmic Reticulum - enzymology Female Gene Deletion Hepatocytes - drug effects Hepatocytes - enzymology Lipase - deficiency Lipase - metabolism Lipid Metabolism - drug effects Mice Microsomes - drug effects Microsomes - metabolism Oleic Acid - pharmacology Phospholipids - metabolism Protein Transport - drug effects Triglycerides - metabolism |
| title | Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression |
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