| First Author | Fryklund C | Year | 2021 |
| Journal | Front Physiol | Volume | 12 |
| Pages | 740666 | PubMed ID | 34630160 |
| Mgi Jnum | J:312665 | Mgi Id | MGI:6786374 |
| Doi | 10.3389/fphys.2021.740666 | Citation | Fryklund C, et al. (2021) EH Domain-Containing 2 Deficiency Restricts Adipose Tissue Expansion and Impairs Lipolysis in Primary Inguinal Adipocytes. Front Physiol 12:740666 |
| abstractText | 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, PPARgamma 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. |
