Endocrine Abstracts

Human omental adipose tissue as a key site for the inflammatory 15-lipoxygenase pathway: Implications for metabolic disease

Margaret J Hill, Philip G McTernan, Nancy F da Silva, Kirsty C McGee, Christine M Kusminski, Adam R Baker, Sudhesh Kumar & Alison L Harte

Warwick Medical School, Clinical Sciences Research Institute, Coventry, UK.

Background and aims: 15-Lipoxygenase (15-LO) is a key, highly regulated enzyme catalysing the oxygenation of arachidonic acid (AA) forming a variety of lipid metabolites that exert diverse pro- and anti-inflammatory properties. To date, no study has addressed the role of 15-LO in human adipose tissue (AT), whilst sub-clinical inflammation is known to represent a key player in the pathogenesis of obesity-mediated type 2 diabetes mellitus (T2DM). Therefore the aims of this study were to (1) investigate the mRNA expression profiles of major pathways involved in AA metabolism in human abdominal subcutaneous (AbSc) and omental (Om) AT depots (2) assess the relative depot specific changes in expression (3) examine the role of adiposity.

Materials and methods: Paired AbSc and Om AT were collected from patients undergoing elective liposuction surgery (Age; 45±1.72 years; lean BMI; 22.91±0.56 kg/m²; obese BMI; 33.51±1.04 kg/m²; n=23) for gene expression analysis by microarray and real time polymerase chain reaction (PCR). Fasted blood was taken to measure metabolic parameters.

Results: Microarray data showed that Om AT had significantly higher expression of 15-LO (P=0.00016) than paired AbSc AT, independent of BMI. In addition, other key elements of AA metabolism; prostaglandin D2 synthase (P=0.000008), leukotriene A4 hydrolase (P=0.00036), prostaglandin endoperoxide synthase 1 (P=0.000001) and cytochrome p450 (P=0.000075) showed significantly higher expression in Om AT. PCR data further corroborated the 15-LO expression profile (AbSc AT: ΔCt 17.10±0.86 and Om AT: ΔCt 6.48±0.37 (P=<0.001)) independent of BMI.

Conclusion: These studies highlight, for the first time, that 15-LO is clearly differentially expressed in human AT. Furthermore that omental AT, which is associated with increased inflammatory response, also has increased mRNA expression of the 15-LO pathway. Taken together, these findings suggest a previously undefined mechanism within human fat that may exacerbate the inflammatory response in obesity mediated T2DM.

Endocrine Abstracts (2008) 15 OC18