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Seitz, S. ; Kwon, Y. ; Hartleben, G. ; Jülg, J.* ; Sekar, R. ; Krahmer, N. ; Najafi, B. ; Loft, A. ; Gancheva, S.* ; Stemmer, K. ; Feuchtinger, A. ; Hrabě de Angelis, M. ; Müller, T.D. ; Mann, M.* ; Blüher, M.* ; Roden, M.* ; Berriel Diaz, M. ; Behrends, C.* ; Gilleron, J.* ; Herzig, S. ; Zeigerer, A.

Hepatic Rab24 controls blood glucose homeostasis via improving mitochondrial plasticity.

Nat. Metab. 1, 1009-1026 (2019)
Postprint DOI PMC
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Zeitschrift Nature metabolism
Quellenangaben Band: 1, Heft: 10, Seiten: 1009-1026 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Cancer (IDC)
Institute of Diabetes and Obesity (IDO)
CF Pathology & Tissue Analytics (CF-PTA)
Institute of Experimental Genetics (IEG)
Research Unit Analytical Pathology (AAP)
POF Topic(s) 90000 - German Center for Diabetes Research
30505 - New Technologies for Biomedical Discoveries
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-501900-254
G-501900-253
G-501900-221
G-501900-251
A-630600-001
G-500600-001
G-500390-001
DOI 10.1038/s42255-019-0124-x
PubMed ID 32694843
Erfassungsdatum 2019-10-17
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