Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1
Identifieur interne : 000B96 ( Main/Exploration ); précédent : 000B95; suivant : 000B97Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1
Auteurs : Sora Kwon [Corée du Sud] ; Ji-Sook Jeon [Corée du Sud] ; Su Bin Kim [Corée du Sud] ; Young-Kwon Hong [États-Unis] ; Curie Ahn [Corée du Sud] ; Jung-Suk Sung [Corée du Sud] ; Inho Choi [Corée du Sud]Source :
- Lipids in Health and Disease [ 1476-511X ] ; 2016.
Abstract
Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown.
HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively.
Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver.
This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.
Url:
DOI: 10.1186/s12944-016-0211-x
PubMed: 26922671
PubMed Central: 4769820
Affiliations:
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type="main">Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1</title><author><name sortKey="Kwon, Sora" sort="Kwon, Sora" uniqKey="Kwon S" first="Sora" last="Kwon">Sora Kwon</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Pharmaceutical Engineering, Hoseo University, Asan, 336-795 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pharmaceutical Engineering, Hoseo University, Asan</wicri:regionArea><wicri:noRegion>Asan</wicri:noRegion></affiliation></author><author><name sortKey="Jeon, Ji Sook" sort="Jeon, Ji Sook" uniqKey="Jeon J" first="Ji-Sook" last="Jeon">Ji-Sook Jeon</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Pharmaceutical Engineering, Hoseo University, Asan, 336-795 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pharmaceutical Engineering, Hoseo University, Asan</wicri:regionArea><wicri:noRegion>Asan</wicri:noRegion></affiliation></author><author><name sortKey="Kim, Su Bin" sort="Kim, Su Bin" uniqKey="Kim S" first="Su Bin" last="Kim">Su Bin Kim</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Pharmaceutical Engineering, Hoseo University, Asan, 336-795 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pharmaceutical Engineering, Hoseo University, Asan</wicri:regionArea><wicri:noRegion>Asan</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name><affiliation wicri:level="2"><nlm:aff id="Aff2">Department of Surgery, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA USA</nlm:aff><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Department of Surgery, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles</wicri:cityArea></affiliation></author><author><name sortKey="Ahn, Curie" sort="Ahn, Curie" uniqKey="Ahn C" first="Curie" last="Ahn">Curie Ahn</name><affiliation wicri:level="4"><nlm:aff id="Aff3">Transplantation Research Institute, Seoul National University, Seoul, Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Transplantation Research Institute, Seoul National University, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region><settlement type="city">Séoul</settlement></placeName><orgName type="university">Université nationale de Séoul</orgName></affiliation></author><author><name sortKey="Sung, Jung Suk" sort="Sung, Jung Suk" uniqKey="Sung J" first="Jung-Suk" last="Sung">Jung-Suk Sung</name><affiliation wicri:level="1"><nlm:aff id="Aff4">Department of Life Science, Dongguk University, Goyang, 410-820 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Life Science, Dongguk University, Goyang</wicri:regionArea><wicri:noRegion>Goyang</wicri:noRegion></affiliation></author><author><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Department of Pharmaceutical Engineering, Hoseo University, Asan, 336-795 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Pharmaceutical Engineering, Hoseo University, Asan</wicri:regionArea><wicri:noRegion>Asan</wicri:noRegion></affiliation></author></analytic><series><title level="j">Lipids in Health and Disease</title><idno type="eISSN">1476-511X</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown.</p></sec><sec><title>Methods</title><p>HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively.</p></sec><sec><title>Results</title><p>Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver.</p></sec><sec><title>Conclusion</title><p>This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Wigle, Jt" uniqKey="Wigle J">JT Wigle</name></author><author><name sortKey="Oliver, G" uniqKey="Oliver G">G Oliver</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dudas, J" uniqKey="Dudas J">J Dudas</name></author><author><name sortKey="Elmaouhoub, A" uniqKey="Elmaouhoub A">A Elmaouhoub</name></author><author><name sortKey="Mansuroglu, T" uniqKey="Mansuroglu T">T Mansuroglu</name></author><author><name sortKey="Batusic, D" uniqKey="Batusic 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Dyer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hartman, Al" uniqKey="Hartman A">AL Hartman</name></author><author><name sortKey="Santos, P" uniqKey="Santos P">P Santos</name></author><author><name sortKey="Dolce, A" uniqKey="Dolce A">A Dolce</name></author><author><name sortKey="Hardwick, Jm" uniqKey="Hardwick J">JM Hardwick</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li><li>États-Unis</li></country><region><li>Californie</li><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement><orgName><li>Université nationale de Séoul</li></orgName></list><tree><country name="Corée du Sud"><noRegion><name sortKey="Kwon, Sora" sort="Kwon, Sora" uniqKey="Kwon S" first="Sora" last="Kwon">Sora Kwon</name></noRegion><name sortKey="Ahn, Curie" sort="Ahn, Curie" uniqKey="Ahn C" first="Curie" last="Ahn">Curie Ahn</name><name sortKey="Choi, Inho" sort="Choi, Inho" uniqKey="Choi I" first="Inho" last="Choi">Inho Choi</name><name sortKey="Jeon, Ji Sook" sort="Jeon, Ji Sook" uniqKey="Jeon J" first="Ji-Sook" last="Jeon">Ji-Sook Jeon</name><name sortKey="Kim, Su Bin" sort="Kim, Su Bin" uniqKey="Kim S" first="Su Bin" last="Kim">Su Bin Kim</name><name sortKey="Sung, Jung Suk" sort="Sung, Jung Suk" uniqKey="Sung J" first="Jung-Suk" last="Sung">Jung-Suk Sung</name></country><country name="États-Unis"><region name="Californie"><name sortKey="Hong, Young Kwon" sort="Hong, Young Kwon" uniqKey="Hong Y" first="Young-Kwon" last="Hong">Young-Kwon Hong</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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