期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 13, 页码 7471-7481出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1918415117
关键词
EHD2 ATPase; caveolae; fatty acid uptake; lipid metabolism; obesity
资金
- Deutsche Forschungsgemeinschaft (DFG) [SFB 958/A7, SFB 958/A12, SFB 958/A13, 278001972TRR 186]
- Initiative and Networking Fund of the Helmholtz Association
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.
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