title: DGAT enzymes are required for triacylglycerol synthesis and lipid droplets in adipocytes.
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 cholesterol-rich 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.
authors.affiliation: Gladstone Institute for Cardiovascular Disease, Department of Medicine, University of California, San Francisco, CA 94158, USA. charris@gladstone.ucsf.edu
authors.forename: Charles A
authors.initials: CA
authors.lastname: Harris
authors.forename: Joel T
authors.initials: JT
authors.lastname: Haas
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Streeper
authors.forename: Scot J
authors.initials: SJ
authors.lastname: Stone
authors.forename: Manju
authors.initials: M
authors.lastname: Kumari
authors.forename: Kui
authors.initials: K
authors.lastname: Yang
authors.forename: Xianlin
authors.initials: X
authors.lastname: Han
authors.forename: Nicholas
authors.initials: N
authors.lastname: Brownell
authors.forename: Richard W
authors.initials: RW
authors.lastname: Gross
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
mesh_terms: D017667:Adipocytes / Q000201:enzymology* / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D014280:Triglycerides / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014280:Triglycerides; C516957:DGAT2 protein, mouse; C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase