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

Frontiers in Physiology

Karin G. Stenkula¹  Claes Fryklund¹  Mario Grossi¹  Eva Degerman¹  Björn Morén¹  Claudia Matthaeus²  Shrenika Shah³ 

[1] Department of Experimental Medical Science, Lund University, Lund, Sweden;National Heart, Lung and Blood Institute, NIH, Bethesda, MD, United States;School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom;

关键词: adipocytes;    EH domain-containing 2;    caveolae;    fatty acids;    adipose tissue;   

DOI  :  10.3389/fphys.2021.740666

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown