title: The molecular mechanism of acylation stimulating protein regulation of adipophilin and perilipin expression: involvement of phosphoinositide 3-kinase and phospholipase C.
abstract: The novel adipokine acylation stimulating protein (ASP) is involved in lipid metabolism and obesity-related disorders. Adipophilin and perilipin, two members of the lipid droplet protein family, participate not only in fat storage within adipocytes, but also in ectopic lipid deposition in the form of cytoplasmic triglyceride (TG) droplets within many types of mammalian cells. During differentiation to mature adipocytes, mechanisms controlling the synthesis and turnover of these lipid droplet proteins are only partially understood, the mechanisms regulating gene/protein expression as yet unidentified. In our previous study, ASP has been shown to regulate adipophilin and perilipin expression to facilitate TG synthesis during 3T3-L1 cell differentiation. Our aim in this study was to provide insight into the physiological importance of phosphoinositide 3-kinase (PI3K) and phospholipase C (PLC) in ASP-triggered alteration of adipophilin and perilipin expression. We found that acute (2.5 h) inhibition of PLC or PI3K results in a decrease in mRNA and protein of perilipin and adipophilin at any time during differentiation. The fact that there is such a rapid change even with mRNA levels suggests a rapid turnover of both mRNA and protein independent of a direct ASP effect. Also, the presence of these inhibitors blocked the ASP stimulatory effects with a maximal decrease in gene and protein expression of adipophilin (-45% and -60%, respectively, P < 0.01) and perilipin (-96% and -63%, respectively, P < 0.01 and P < 0.05). These findings provide further understanding of the adipogenic properties of ASP in adipocytes.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Zhou-Yang
authors.initials: ZY
authors.lastname: Jiao
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Han-Hua
authors.initials: HH
authors.lastname: Lin
authors.forename: Katherine
authors.initials: K
authors.lastname: Cianflone
mesh_terms: D041721:3T3-L1 Cells; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins; D003176:Complement C3; D004591:Electrophoresis, Polyacrylamide Gel; D004963:Estrenes / Q000494:pharmacology; D015151:Immunoblotting; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008565:Membrane Proteins; D051379:Mice; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000070778:Perilipin-1; D000070780:Perilipin-2; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011760:Pyrrolidinones / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002352:Carrier Proteins; D003176:Complement C3; D004963:Estrenes; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D000070778:Perilipin-1; D000070780:Perilipin-2; D019869:Phosphatidylinositol 3-Kinases; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D011760:Pyrrolidinones; D014280:Triglycerides; D010738:Type C Phospholipases; D000077191:Wortmannin; C545610:C3 protein, mouse; C000602983:Plin2 protein, mouse; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione