RT Journal Article
SR Electronic
T1 EHD2-mediated restriction of caveolar dynamics regulates cellular lipid uptake
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 511709
DO 10.1101/511709
A1 Matthäus, Claudia
A1 Lahmann, Ines
A1 Kunz, Séverine
A1 Jonas, Wenke
A1 Melo, Arthur Alves
A1 Lehmann, Martin
A1 Larsson, Elin
A1 Lundmark, Richard
A1 Haucke, Volker
A1 Müller, Dominik N.
A1 Schürmann, Annette
A1 Birchmeier, Carmen
A1 Daumke, Oliver
YR 2019
UL http://biorxiv.org/content/early/2019/01/04/511709.abstract
AB 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. We found that global genetic ablation of EHD2 in mice led to increased fat deposits in several organs. This organismic phenotype was paralleled at the cellular level by an increased lipid uptake via a CD36-dependent pathway, an elevated number of detached caveolae and higher caveolar mobility. Following a high fat diet, various enzymes involved in de novo fatty acid synthesis were down-regulated in EHD2 KO mice. Furthermore, EHD2 expression itself was down-regulated in the visceral fat of two obese mouse models and in diet-induced obesity. Thus, EHD2 controls a cell-autonomous, caveolae-dependent lipid uptake pathway, implicating a role of EHD2 in fat accumulation and obesity.