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

Lila González-Hódar, Jeffrey G. McDonald, Goncalo Vale, Bonne M. Thompson, Ana María Figueroa, Pablo J. Tapia, Fermín Robledo, Anil K. Agarwal, Abhimanyu Garg, Jay D. Horton, Víctor Cortés

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number166167
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1867
Issue number9
DOIs
StatePublished - Sep 1 2021

Keywords

  • Adipogenesis
  • Caveolae
  • Lipids
  • Lipodystrophy
  • Plasma membrane
  • agpat2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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