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  Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity

Seitz, S., Kwon, Y., Hartleben, G., Jülg, J., Sekar, R., Krahmer, N., et al. (2019). Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity. NATURE METABOLISM, 1(10), 1009-1026. doi:10.1038/s42255-019-0124-x.

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Genre: Journal Article

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 Creators:
Seitz, Susanne1, Author
Kwon, Yun1, Author
Hartleben, Goetz1, Author
Jülg, Julia1, Author
Sekar, Revathi1, Author
Krahmer, Natalie2, Author              
Najafi, Bahar1, Author
Loft, Anne1, Author
Gancheva, Sofiya1, Author
Stemmer, Kerstin1, Author
Feuchtinger, Annette1, Author
de Angelis, Martin Hrabe1, Author
Müller, Timo D.1, Author
Mann, Matthias2, Author              
Blüher, Matthias1, Author
Roden, Michael1, Author
Diaz, Mauricio Berriel1, Author
Behrends, Christian1, Author
Gilleron, Jerome1, Author
Herzig, Stephan1, Author
Zeigerer, Anja1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: NONALCOHOLIC FATTY LIVER; INSULIN-RESISTANCE; IN-VITRO; PROTEIN; AUTOPHAGY; FISSION; LOCALIZATION; DYSFUNCTION; PROGRESSION; HEPATOCYTES
 Abstract: Non-alcoholic fatty liver disease (NAFLD) represents a key feature of obesity-related type 2 diabetes with increasing prevalence worldwide. To our knowledge, no treatment options are available to date, paving the way for more severe liver damage, including cirrhosis and hepatocellular carcinoma. Here, we show an unexpected function for an intracellular trafficking regulator, the small Rab GTPase Rab24, in mitochondrial fission and activation, which has an immediate impact on hepatic and systemic energy homeostasis. RAB24 is highly upregulated in the livers of obese patients with NAFLD and positively correlates with increased body fat in humans. Liver-selective inhibition of Rab24 increases autophagic flux and mitochondrial connectivity, leading to a strong improvement in hepatic steatosis and a reduction in serum glucose and cholesterol levels in obese mice. Our study highlights a potential therapeutic application of trafficking regulators, such as RAB24, for NAFLD and establishes a conceptual functional connection between intracellular transport and systemic metabolic dysfunction.

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Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 28
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000500746000012
DOI: 10.1038/s42255-019-0124-x
 Degree: -

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Title: NATURE METABOLISM
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 1 (10) Sequence Number: - Start / End Page: 1009 - 1026 Identifier: -