title: Depot-specific prostaglandin synthesis in human adipose tissue: a novel possible mechanism of adipogenesis.
abstract: Despite the magnitude of the obesity epidemic, the mechanisms that contribute to increases in fat mass and to differences in fat depots are still poorly understood. Prostanoids have been proposed as potent adipogenic hormones, e.g. metabolites of prostaglandin J2 (PGJ2) bind and activate PPARgamma. We hypothesize that an altered expression of enzymes in PGJ2 synthesis may represent a novel pathogenic mechanism in human obesity. We characterized adipose depot-specific expression of enzymes in PGJ2 synthesis, prostaglandin transporter and PPARgamma isoforms. Paired omental and subcutaneous adipose tissue samples were obtained from 26 women undergoing elective abdominal surgery and gene expression examined in whole tissue and cultured preadipocytes using an Affymetrix cDNA microarray technique and validated with quantitative real-time PCR. All enzymes involved in prostaglandin synthesis were expressed in both adipose tissues. Expression of prostaglandin synthase-1 (PGHS1), prostaglandin D synthase (PTGDS), human prostaglandin transporter (hPGT) and PPARgamma2 was higher in OM adipose tissue compared to SC, whereas 17beta-hydroxysteroid dehydrogenase 5 (AKR1C3) showed predominance in SC adipose tissue. In SC adipose tissue, PGHS1 mRNA expression increased with BMI. The differential, depot-specific expression of key enzymes involved in transport, synthesis and metabolism of prostaglandins may have an important impact upon fat cell biology and may help to explain some of the observed depot-specific differences. In addition, the positive correlation between PGHS1 and BMI offers the novel hypothesis that the regulation of PG synthesis may have a role in determining fat distribution in human obesity.
authors.affiliation: Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Queen Elizabeth Hospital, Birmingham, B15 2TH, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: Iwona J
authors.initials: IJ
authors.lastname: Bujalska
authors.forename: Jeremy W
authors.initials: JW
authors.lastname: Tomlinson
authors.forename: Dave M
authors.initials: DM
authors.lastname: Smith
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000005:Abdomen; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000074425:Aldo-Keto Reductase Family 1 Member C3; D050218:Body Fat Distribution; D015992:Body Mass Index; D048429:Cell Size; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D054834:Lipocalins; D008875:Middle Aged; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D009852:Omentum / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D011457:Prostaglandins D / Q000096:biosynthesis / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000473:pathology
chemical_list: D054834:Lipocalins; D027361:Organic Anion Transporters; D047495:PPAR gamma; D011453:Prostaglandins; D011457:Prostaglandins D; C503526:SLCO2A1 protein, human; C037112:9-deoxy-delta-9-prostaglandin D2; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2