title: Phosphatidate phosphatase-1 is functionally conserved in lipid synthesis and storage from human to yeast.
abstract: Phosphatidate phosphatase-1 (PAP1) enzymes (yeast Pah1p/Smp2p, mammalian lipin1-3) have a key role in lipid homeostasis by controlling the relative proportions of its substrate phosphatidate (PA) and its product diacylglycerol (DAG). Recent investigation shows that mammalian lipin-1 complements phenotypes exhibited by yeast pah1Δ mutant cells, which indicates the functions of PAP1 enzymes are evolutionarily conserved. The observation was confirmed after transformation of human LPIN1 into PAH1-defective yeast, which resulted in human LPIN1-induced accumulation of triacylglycerol (TAG )and lipid droplet formation. In double mutants lacking Tgl3p and Tgl4p, overexpression of PAH1 or LPIN1 induced TAG accumulation and excessive obesity. Furthermore, the obese yeast was used as a model to study the anti-obesity effects of PAP1 activity inhibitors, including propranolol and clenbuterol. The data showed that the inhibitors significantly suppressed TAG accumulation and lipid droplets formation. These findings demonstrate that LPIN1 plays a functional role in lipid synthesis and storage, a role which is highly conserved from human to yeast. Inhibition of TAG synthesis will become an efficacious treatment strategy for obesity and our excessive obesity model will provide a very useful tool for discovery of new anti-obesity drugs in the future.
authors.affiliation: Donghua University College of Chemistry, Chemical Engineering and Biotechnology 2999 Renmin Road Shanghai 201620 China.
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Fang
authors.affiliation: East China University of Science and Technology State Key Laboratory of Bioreactor Engineering 130 Meilong Road Shanghai 200237 China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Donghua University College of Chemistry, Chemical Engineering and Biotechnology 2999 Renmin Road Shanghai 201620 China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Du
authors.affiliation: East China University of Science and Technology State Key Laboratory of Bioreactor Engineering 130 Meilong Road Shanghai 200237 China.
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.affiliation: Donghua University College of Chemistry, Chemical Engineering and Biotechnology 2999 Renmin Road Shanghai 201620 China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D019440:Anti-Obesity Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects; D009154:Mutation; D000073718:Pancreatitis-Associated Proteins; D010711:Phosphatidate Phosphatase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D000073718:Pancreatitis-Associated Proteins; D010743:Phospholipids; C000612141:REG3A protein, human; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; D008049:Lipase; C476342:TGL3 protein, S cerevisiae; C506904:Tgl4 protein, S cerevisiae; C485999:LPIN1 protein, human; C079831:PAH1 protein, S cerevisiae; D010711:Phosphatidate Phosphatase
keywords: LPIN1; PAH1; Phosphatidate phosphatase; obesity yeast model; triacylglycerol