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EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake

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Item Type:Article
Title:EHD2-mediated restriction of caveolar dynamics regulates cellular fatty acid uptake
Creators Name:Matthaeus, C. and Lahmann, I. and Kunz, S. and Jonas, W. and Melo, A.A. and Lehmann, M. and Larsson, E. and Lundmark, R. and Kern, M. and Blüher, M. and Olschowski, H. and Kompa, J. and Brügger, B. and Müller, D.N. and Haucke, V. and Schürmann, A. and Birchmeier, C. and Daumke, O.
Abstract:Eps15-homology domain containing protein 2 (EHD2) is a dynamin-related ATPase located at the neck of caveolae, but its physiological function has remained unclear. Here, we found that global genetic ablation of EHD2 in mice leads to increased lipid droplet size in fat tissue. This organismic phenotype was paralleled at the cellular level by increased fatty acid uptake via a caveolae- and CD36-dependent pathway that also involves dynamin. Concomitantly, elevated numbers of detached caveolae were found in brown and white adipose tissue lacking EHD2, and increased caveolar mobility in mouse embryonic fibroblasts. EHD2 expression itself was down-regulated in the visceral fat of two obese mouse models and obese patients. Our data suggest that EHD2 controls a cell-autonomous, caveolae-dependent fatty acid uptake pathway and imply that low EHD2 expression levels are linked to obesity.
Keywords:EHD2 ATPase, Caveolae, Fatty Acid Uptake, Lipid Metabolism, Obesity, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences
Volume:117
Number:13
Page Range:7471-7481
Date:31 March 2020
Official Publication:https://doi.org/10.1073/pnas.1918415117
PubMed:View item in PubMed
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https://edoc.mdc-berlin.de/18146/Preprint version

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