Regulation of Liver Metabolism by the Endosomal GTPase Rab5
Name
Zeigerer-2015-Regulation of Liver.pdf
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3.18 MB
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Author(s)
Zeigerer, Anja
Bogorad, Roman L.
Sharma, Kirti
Gilleron, Jerome
Seifert, Sarah
Sales, Susanne
Berndt, Nikolaus
Bulik, Sascha
Marsico, Giovanni
D’Souza, Rochelle C.J.
Date Issued
April 2015
Journal
Cell Reports
Publisher
Elsevier
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2015.04.018
