Regulation of Liver Metabolism by the Endosomal GTPase Rab5
The liver maintains glucose and lipid homeostasis by adapting its metabolic activity to the energy needs of the organism. Communication between hepatocytes and extracellular environment via endocytosis is key to such homeostasis. Here, we addressed the question of whether endosomes are required for...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101702 |
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| author | Zeigerer, Anja Bogorad, Roman L. Sharma, Kirti Gilleron, Jerome Seifert, Sarah Sales, Susanne Berndt, Nikolaus Bulik, Sascha Marsico, Giovanni D’Souza, Rochelle C.J. Lakshmanaperumal, Naharajan Meganathan, Kesavan Natarajan, Karthick Sachinidis, Agapios Dahl, Andreas Holzhütter, Hermann-Georg Shevchenko, Andrej Mann, Matthias Koteliansky, Victor Zerial, Marino Bogorad, Roman |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Zeigerer, Anja Bogorad, Roman L. Sharma, Kirti Gilleron, Jerome Seifert, Sarah Sales, Susanne Berndt, Nikolaus Bulik, Sascha Marsico, Giovanni D’Souza, Rochelle C.J. Lakshmanaperumal, Naharajan Meganathan, Kesavan Natarajan, Karthick Sachinidis, Agapios Dahl, Andreas Holzhütter, Hermann-Georg Shevchenko, Andrej Mann, Matthias Koteliansky, Victor Zerial, Marino Bogorad, Roman |
| author_sort | Zeigerer, Anja |
| collection | MIT |
| description | The liver maintains glucose and lipid homeostasis by adapting its metabolic activity to the energy needs of the organism. Communication between hepatocytes and extracellular environment via endocytosis is key to such homeostasis. Here, we addressed the question of whether endosomes are required for gluconeogenic gene expression. We took advantage of the loss of endosomes in the mouse liver upon Rab5 silencing. Strikingly, we found hepatomegaly and severe metabolic defects such as hypoglycemia, hypercholesterolemia, hyperlipidemia, and glycogen accumulation that phenocopied those found in von Gierke’s disease, a glucose-6-phosphatase (G6Pase) deficiency. G6Pase deficiency alone can account for the reduction in hepatic glucose output and glycogen accumulation as determined by mathematical modeling. Interestingly, we uncovered functional alterations in the transcription factors, which regulate G6Pase expression. Our data highlight a requirement of Rab5 and the endosomal system for the regulation of gluconeogenic gene expression that has important implications for metabolic diseases. |
| first_indexed | 2024-09-23T11:12:30Z |
| format | Article |
| id | mit-1721.1/101702 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:12:30Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1017022022-09-27T17:52:05Z Regulation of Liver Metabolism by the Endosomal GTPase Rab5 Zeigerer, Anja Bogorad, Roman L. Sharma, Kirti Gilleron, Jerome Seifert, Sarah Sales, Susanne Berndt, Nikolaus Bulik, Sascha Marsico, Giovanni D’Souza, Rochelle C.J. Lakshmanaperumal, Naharajan Meganathan, Kesavan Natarajan, Karthick Sachinidis, Agapios Dahl, Andreas Holzhütter, Hermann-Georg Shevchenko, Andrej Mann, Matthias Koteliansky, Victor Zerial, Marino Bogorad, Roman Koch Institute for Integrative Cancer Research at MIT Bogorad, Roman L. The liver maintains glucose and lipid homeostasis by adapting its metabolic activity to the energy needs of the organism. Communication between hepatocytes and extracellular environment via endocytosis is key to such homeostasis. Here, we addressed the question of whether endosomes are required for gluconeogenic gene expression. We took advantage of the loss of endosomes in the mouse liver upon Rab5 silencing. Strikingly, we found hepatomegaly and severe metabolic defects such as hypoglycemia, hypercholesterolemia, hyperlipidemia, and glycogen accumulation that phenocopied those found in von Gierke’s disease, a glucose-6-phosphatase (G6Pase) deficiency. G6Pase deficiency alone can account for the reduction in hepatic glucose output and glycogen accumulation as determined by mathematical modeling. Interestingly, we uncovered functional alterations in the transcription factors, which regulate G6Pase expression. Our data highlight a requirement of Rab5 and the endosomal system for the regulation of gluconeogenic gene expression that has important implications for metabolic diseases. Germany. Federal Ministry of Education and Research Max Planck Society for the Advancement of Science Deutsche Forschungsgemeinschaf 2016-03-14T23:43:34Z 2016-03-14T23:43:34Z 2015-04 2015-02 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/101702 Zeigerer, Anja, Roman L. Bogorad, Kirti Sharma, Jerome Gilleron, Sarah Seifert, Susanne Sales, Nikolaus Berndt, et al. “Regulation of Liver Metabolism by the Endosomal GTPase Rab5.” Cell Reports 11, no. 6 (May 2015): 884–892. en_US http://dx.doi.org/10.1016/j.celrep.2015.04.018 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Zeigerer, Anja Bogorad, Roman L. Sharma, Kirti Gilleron, Jerome Seifert, Sarah Sales, Susanne Berndt, Nikolaus Bulik, Sascha Marsico, Giovanni D’Souza, Rochelle C.J. Lakshmanaperumal, Naharajan Meganathan, Kesavan Natarajan, Karthick Sachinidis, Agapios Dahl, Andreas Holzhütter, Hermann-Georg Shevchenko, Andrej Mann, Matthias Koteliansky, Victor Zerial, Marino Bogorad, Roman Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title | Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title_full | Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title_fullStr | Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title_full_unstemmed | Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title_short | Regulation of Liver Metabolism by the Endosomal GTPase Rab5 |
| title_sort | regulation of liver metabolism by the endosomal gtpase rab5 |
| url | http://hdl.handle.net/1721.1/101702 |
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