DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes

Charles A. Harris, Joel T. Haas, Ryan S. Streeper, Scot J. Stone, Manju Kumari, Kui Yang, Xianlin Han, Nicholas Brownell, Richard W. Gross, Rudolf Zechner, Robert V. Farese

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

The total contribution of the acyl CoA:diacylglycerol acyltransferase (DGAT) enzymes, DGAT1 and DGAT2, to mammalian triacylglycerol (TG) synthesis has not been determined. Similarly, whether DGAT enzymes are required for lipid droplet (LD) formation is unknown. In this study, we examined the requirement for DGAT enzymes in TG synthesis and LDs in differentiated adipocytes with genetic deletions of DGAT1 and DGAT2. Adipocytes with a single deletion of either enzyme were capable of TG synthesis and LD formation. In contrast, adipocytes with deletions of both DGATs were severely lacking in TG and did not have LDs, indicating that DGAT1 and DGAT2 account for nearly all TG synthesis in adipocytes and appear to be required for LD formation during adipogenesis. DGAT enzymes were not absolutely required for LD formation in mammalian cells, however; macrophages deficient in both DGAT enzymes were able to form LDs when incubated with cholesterolrich lipoproteins. Although adipocytes lacking both DGATs had no TG or LDs, they were fully differentiated by multiple criteria. Our findings show that DGAT1 and DGAT2 account for the vast majority of TG synthesis in mice, and DGAT function is required for LDs in adipocytes, but not in all cell types.

Original languageEnglish (US)
Pages (from-to)657-667
Number of pages11
JournalJournal of lipid research
Volume52
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Adipogenesis
  • Diacylglycerol
  • Lipases
  • Macrophages
  • Neutral lipids
  • Perilipin
  • Phospholipids
  • Sterol esters

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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