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Primary cilia are dysfunctional in obese adipose-derived mesenchymal stem cells

  • Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases.
Metadaten
Author:Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Samira Catharina Hoock, Susanne Roth, Ulrikke Kielland-Kaisen, Dörthe BrüggmannORCiDGND, Christine Solbach, Frank LouwenGND, Juping Yuan
URN:urn:nbn:de:hebis:30:3-463866
DOI:https://doi.org/10.1016/j.stemcr.2017.12.022
ISSN:2213-6711
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/29396182
Parent Title (English):Stem cell reports
Publisher:Cell Press ; Elsevier
Place of publication:Maryland Heights, MO ; [New York, NY]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/01/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/05/15
Tag:Aurora A; IL-6; TNF-α; adipose-derived mesenchymal stem cells; hedgehog signaling; obesity; primary cilium
Volume:10
Issue:2
Page Number:17
First Page:583
Last Page:599
Note:
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS-PPN:434445010
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Open-Access-Publikationsfonds:Medizin
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0