Adipocytes play a central role in energy balance, and dysfunctional adipose tissue severely
affects systemic energy homeostasis. The ATPase EH domain-containing 2 (EHD2) has
previously been shown to regulate caveolae, plasma membrane-specific domains that are
involved in lipid uptake and signal transduction. Here, we investigated the role of EHD2 in
adipocyte function. We demonstrate that EHD2 protein expression is highly upregulated at the
onset of triglyceride accumulation during adipocyte differentiation. siRNA-mediated EHD2-
silencing affected the differentiation process, and impaired both insulin sensitivity, lipid
storage capacity and lipolysis. Fluorescence imaging revealed localization of EHD2 to
caveolae, close to cell surface-associated lipid droplets in primary human adipocytes. These
lipid droplets stained positive for glycerol transporter AQP7 and phosphorylated perilipin-1
following adrenergic stimulation. Further, EHD2 overexpression in human adipocytes
increased the lipolytic signaling and suppressed the activity of transcription factor PPAR¿.
Overall, these data suggest that EHD2 plays a key role for adipocyte function.

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