Depot-specific prostaglandin synthesis in human adipose tissue: A novel possible mechanism of adipogenesis
详细信息 查看全文
- 作者：Marcus Quinkler ; Iwona J. Bujalska ; Jeremy W. Tomlinson ; Dave M. Smith and Paul M. Stewart
- 关键词：Obesity ; Prostaglandins ; PPAR gamma ; AKR1C3 ; Omental and subcutaneous fat
- 刊名：Gene
- 出版年：2006
- 出版时间：1 October 2006
- 年：2006
- 卷：380
- 期：2
- 页码：137-143
- 全文大小：289 K
文摘
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 PPARγ. 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 PPARγ 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 PPARγ2 was higher in OM adipose tissue compared to SC, whereas 17β-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.