title: Distinct roles of the phosphatidate phosphatases lipin 1 and 2 during adipogenesis and lipid droplet biogenesis in 3T3-L1 cells.
abstract: Lipins are evolutionarily conserved Mg(2+)-dependent phosphatidate phosphatase (PAP) enzymes with essential roles in lipid biosynthesis. Mammals express three paralogues: lipins 1, 2, and 3. Loss of lipin 1 in mice inhibits adipogenesis at an early stage of differentiation and results in a lipodystrophic phenotype. The role of lipins at later stages of adipogenesis, when cells initiate the formation of lipid droplets, is less well characterized. We found that depletion of lipin 1, after the initiation of differentiation in 3T3-L1 cells but before the loading of lipid droplets with triacylglycerol, results in a reciprocal increase of lipin 2, but not lipin 3. We generated 3T3-L1 cells where total lipin protein and PAP activity levels are down-regulated by the combined depletion of lipins 1 and 2 at day 4 of differentiation. These cells still accumulated triacylglycerol but displayed a striking fragmentation of lipid droplets without significantly affecting their total volume per cell. This was due to the lack of the PAP activity of lipin 1 in adipocytes after day 4 of differentiation, whereas depletion of lipin 2 led to an increase of lipid droplet volume per cell. We propose that in addition to their roles during early adipogenesis, lipins also have a role in lipid droplet biogenesis.
authors.affiliation: From the Cambridge Institute for Medical Research, University of Cambridge, CB2 0XY Cambridge, United Kingdom.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sembongi
authors.forename: Merce
authors.initials: M
authors.lastname: Miranda
authors.forename: Gil-Soo
authors.initials: GS
authors.lastname: Han
authors.forename: Stylianos
authors.initials: S
authors.lastname: Fakas
authors.forename: Neil
authors.initials: N
authors.lastname: Grimsey
authors.forename: Joan
authors.initials: J
authors.lastname: Vendrell
authors.forename: George M
authors.initials: GM
authors.lastname: Carman
authors.forename: Symeon
authors.initials: S
authors.lastname: Siniossoglou
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D008055:Lipids / Q000096:biosynthesis*; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008055:Lipids; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014280:Triglycerides; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; C540254:Lipin 2 protein, mouse
keywords: Adipocyte; Lipids; Lipin; Mouse; Phosphatase; Phosphatidate; Triacylglycerol