Journal
MOLECULAR BIOLOGY OF THE CELL
Volume 30, Issue 10, Pages 1147-1159Publisher
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E18-10-0680
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Funding
- Swedish Research Council [2013-3542]
- Swedish Research Council (Strategic Research Area Exodiab) [2009-1039]
- Swedish Foundation for Strategic Research [IRC15-0067]
- Novo Nordisk [NNF17OC0027054]
- Swedish Diabetes Foundation
- Crafoord Foundation
- Albert Pahlsson Foundation
- Royal Physiographic Society in Lund
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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 up-regulated at the onset of triglyceride accumulation during adipocyte differentiation. Small interfering RNA-mediated EHD2 silencing affected the differentiation process and impaired 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 aquaporin 7 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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