Integrated lipidomics and RNA sequencing analysis reveal novel changes during 3T3-L1 cell adipogenesis

PeerJ. 2022 May 3:10:e13417. doi: 10.7717/peerj.13417. eCollection 2022.


After adipogenic differentiation, key regulators of adipogenesis are stimulated and cells begin to accumulate lipids. To identify specific changes in lipid composition and gene expression patterns during 3T3-L1 cell adipogenesis, we carried out lipidomics and RNA sequencing analysis of undifferentiated and differentiated 3T3-L1 cells. The analysis revealed significant changes in lipid content and gene expression patterns during adipogenesis. Slc2a4 was up-regulated, which may enhance glucose transport; Gpat3, Agpat2, Lipin1 and Dgat were also up-regulated, potentially to enrich intracellular triacylglycerol (TG). Increased expression levels of Pnpla2, Lipe, Acsl1 and Lpl likely increase intracellular free fatty acids, which can then be used for subsequent synthesis of other lipids, such as sphingomyelin (SM) and ceramide (Cer). Enriched intracellular diacylglycerol (DG) can also provide more raw materials for the synthesis of phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), ether-PE, and ether-PC, whereas high expression of Pla3 may enhance the formation of lysophophatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Therefore, in the process of adipogenesis of 3T3-L1 cells, a series of genes are activated, resulting in large changes in the contents of various lipid metabolites in the cells, especially TG, DG, SM, Cer, PI, PC, PE, etherPE, etherPC, LPC and LPE. These findings provide a theoretical basis for our understanding the pathophysiology of obesity.

Keywords: 3T3-L1; Adipogenesis; Ceramide; Diacylglycerol; Lipidomics; Phospholipid; Sphingomyelin; Triacylglycerol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Acylglycerol-3-Phosphate O-Acyltransferase
  • 3T3-L1 Cells
  • Adipogenesis* / genetics
  • Animals
  • Ceramides
  • Lecithins
  • Lipidomics*
  • Mice
  • Sequence Analysis, RNA


  • Lecithins
  • Ceramides
  • GPAT3 protein, mouse
  • 1-Acylglycerol-3-Phosphate O-Acyltransferase

Grants and funding

This work was supported by the National Science Foundation for Young Scientists of China (31702088), the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding (2019B030301010), the Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes (2019KSYS011), and the Foshan University Initiative Scientific Research Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.