4.7 Article

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

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ELSEVIER
DOI: 10.1016/j.bbadis.2021.166167

关键词

Adipogenesis; Caveolae; Lipids; Plasma membrane; agpat2; Lipodystrophy

资金

  1. FONDECYT [1181214]
  2. National Institutes of Health [HL-20948]
  3. CONICYT Doctoral Fellowship [21171491]

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The adipocytes from Agpat2(-/-) mice have impaired adipogenesis and fewer caveolae, but insulin signaling remains conserved. Lipid composition changes during adipogenesis in wild type adipocytes while levels of main phospholipids decrease in both genotypes.
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.

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