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EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes

Morén, Björn LU ; Hansson, Björn LU ; Negoita, Florentina LU ; Fryklund, Claes LU ; Lundmark, Richard; Göransson, Olga LU and Stenkula, Karin G. LU (2019) In Molecular Biology of the Cell 30(10). p.1147-1159
Abstract

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... (More)

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 PPARγ. Overall, these data suggest that EHD2 plays a key role for adipocyte function.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Biology of the Cell
volume
30
issue
10
pages
13 pages
publisher
American Society for Cell Biology
external identifiers
  • scopus:85065230221
ISSN
1059-1524
DOI
10.1091/mbc.E18-10-0680
language
English
LU publication?
yes
id
521e6dbd-60a3-473e-953a-b4437462270f
date added to LUP
2019-05-24 11:53:53
date last changed
2019-06-11 04:06:19
@article{521e6dbd-60a3-473e-953a-b4437462270f,
  abstract     = {<p>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 PPARγ. Overall, these data suggest that EHD2 plays a key role for adipocyte function.</p>},
  author       = {Morén, Björn and Hansson, Björn and Negoita, Florentina and Fryklund, Claes and Lundmark, Richard and Göransson, Olga and Stenkula, Karin G.},
  issn         = {1059-1524},
  language     = {eng},
  number       = {10},
  pages        = {1147--1159},
  publisher    = {American Society for Cell Biology},
  series       = {Molecular Biology of the Cell},
  title        = {EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes},
  url          = {http://dx.doi.org/10.1091/mbc.E18-10-0680},
  volume       = {30},
  year         = {2019},
}