| First Author | González-Hódar L | Year | 2021 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1867 |
| Issue | 9 | Pages | 166167 |
| PubMed ID | 33989739 | Mgi Jnum | J:320454 |
| Mgi Id | MGI:6726980 | Doi | 10.1016/j.bbadis.2021.166167 |
| Citation | Gonzalez-Hodar L, et al. (2021) Decreased caveolae in AGPAT2 lacking adipocytes is independent of changes in cholesterol or sphingolipid levels: A whole cell and plasma membrane lipidomic analysis of adipogenesis. Biochim Biophys Acta Mol Basis Dis 1867(9):166167 |
| abstractText | BACKGROUND: Adipocytes from lipodystrophic Agpat2(-/-) mice have impaired adipogenesis and fewer caveolae. Herein, we examined whether these defects are associated with changes in lipid composition or abnormal levels of caveolae-associated proteins. Lipidome changes were quantified in differentiated Agpat2(-/-) adipocytes to identify lipids with potential adipogenic roles. METHODS: Agpat2(-/-) and wild type brown preadipocytes were differentiated in vitro. Plasma membrane was purified by ultracentrifugation. Number of caveolae and caveolae-associated proteins, as well as sterol, sphingolipid, and phospholipid lipidome were determined across differentiation. RESULTS: Differentiated Agpat2(-/-) adipocytes had decreased caveolae number but conserved insulin signaling. Caveolin-1 and cavin-1 levels were equivalent between Agpat2(-/-) and wild type adipocytes. No differences in PM cholesterol and sphingolipids abundance were detected between genotypes. Levels of phosphatidylserine at day 10 of differentiation were increased in Agpat2(-/-) adipocytes. Wild type adipocytes had increased whole cell triglyceride, diacylglycerol, phosphatidylglycerol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, and trihexosyl ceramide, and decreased 24,25-dihydrolanosterol and sitosterol, as a result of adipogenic differentiation. By contrast, adipogenesis did not modify whole cell neutral lipids but increased lysophosphatidylcholine, sphingomyelin, and trihexosyl ceramide levels in Agpat2(-/-) adipocytes. Unexpectedly, adipogenesis decreased PM levels of main phospholipids in both genotypes. CONCLUSION: In Agpat2(-/-) adipocytes, decreased caveolae is not associated with changes in PM cholesterol nor sphingolipid levels; however, increased PM phosphatidylserine content may be implicated. Abnormal lipid composition is associated with the adipogenic abnormalities of Agpat2 -/- adipocytes but does not prevent insulin signaling. |
