title: Stable expression of lipocalin-type prostaglandin D synthase in cultured preadipocytes impairs adipogenesis program independently of endogenous prostanoids.
abstract: Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD(2) and its non-enzymatic dehydration products, PGJ(2) series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD(2) and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction. The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD(2) from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE(2) remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize Δ(12)-PGJ(2) increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor γ (PPARγ) agonists including troglitazone and Δ(12)-PGJ(2). Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPARγ signaling pathway without the contribution of endogenous pro-adipogenic prostanoids.
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504, Japan.
authors.forename: Mohammad Salim
authors.initials: MS
authors.lastname: Hossain
authors.forename: Abu Asad
authors.initials: AA
authors.lastname: Chowdhury
authors.forename: Mohammad Sharifur
authors.initials: MS
authors.lastname: Rahman
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishimura
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Jisaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nagaya
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shono
authors.forename: Kazushige
authors.initials: K
authors.lastname: Yokota
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: C477819:15-deoxyprostaglandin J2; D052246:Cyclooxygenase 2 Inhibitors; D054834:Lipocalins; D047495:PPAR gamma; D011453:Prostaglandins; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D001241:Aspirin; D015230:Prostaglandin D2