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Eva Degerman

Eva Degerman

Professor

Eva Degerman

EH Domain-Containing 2 Deficiency Restricts Adipose Tissue Expansion and Impairs Lipolysis in Primary Inguinal Adipocytes

Author

  • Claes Fryklund
  • Björn Morén
  • Shrenika Shah
  • Mario Grossi
  • Eva Degerman
  • Claudia Matthaeus
  • Karin G. Stenkula

Summary, in English

Lipid uptake can be facilitated via caveolae, specific plasma membrane invaginations abundantly expressed in adipocytes. The dynamin-related protein EH domain-containing 2 (EHD2) stabilizes caveolae at the cell surface. Here, we have examined the importance of EHD2 for lipid handling using primary adipocytes isolated from EHD2 knockout (Ehd2−/−) C57BL6/N mice. Following high-fat diet (HFD) feeding, we found a clear impairment of epididymal, but not inguinal, adipose tissue expansion in Ehd2−/− compared with Ehd2+/+ (WT) mice. Cell size distribution analysis revealed that Ehd2−/− mice had a lower proportion of small adipocytes, and an accumulation of medium-sized adipocytes in both epididymal and inguinal adipose tissue. Further, PPARγ activity, FABP4 and caveolin-1 expression were decreased in adipocytes isolated from Ehd2−/− mice. Inguinal adipocytes isolated from Ehd2−/− mice displayed reduced lipolysis in response to beta adrenergic receptor agonist, which was associated with reduced phosphorylation of perilipin-1 and hormone sensitive lipase (HSL). This impairment could not be rescued using a cAMP analog, indicating that impaired lipolysis in Ehd2−/− primary adipocytes likely occurs at the level of, or downstream of, protein kinase A (PKA). Altogether, these findings pinpoint the importance of EHD2 for maintained intracellular lipid metabolism, and emphasize differences in mechanisms regulating lipid handling in various adipose-tissue depots.

Department/s

  • Glucose Transport and Protein Trafficking
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiology
  • Insulin Signal Transduction

Publishing year

2021-09-24

Language

English

Publication/Series

Frontiers in Physiology

Volume

12

Document type

Journal article

Publisher

Frontiers Media S. A.

Topic

  • Endocrinology and Diabetes

Keywords

  • adipocytes
  • adipose tissue
  • caveolae
  • EH domain-containing 2
  • fatty acids

Status

Published

Research group

  • Glucose Transport and Protein Trafficking
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1664-042X