Endocrine Abstracts (2012) 28 P184

The adipocyte as an active source of PLA2 isoforms influenced by adiposity, depot specificity and Type 2 Diabetes Mellitus

Warunee Kumsaiyai1, Alison Harte1, Ponnusamy Saravanan2, Ioannis Kyrou1, Nasser Aldaghri3, Omar Al-Attas3, Sudhesh Kumar1, Gyanendra Tripathi1 & Philip McTernan1

1Division of Metabolic & Vascular Health, Warwick Medical School, University of Warwick, Coventry, United Kingdom; 2University of Warwick & George Eliot Hospital, Warwick Medical School, University of Warwick, Coventry, United Kingdom; 3Biomarkers Research Program and Center of Excellence in Biotechnology Research, King Saud University, Riyadh, Saudi Arabia.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 super family of enzymes that hydrolyse phospholipids, and is upregulated in arterial inflammation, obesity and cardiovascular disease. Secreted soluble Lp-PLA2 (sPLA2) increases arterial inflammation in addition to cytosolic calcium dependent PLA2 (cPLA2) and calcium independent PLA2 (iPLA2). These studies examined the influence of adipose tissue (AT) depots (abdominal subcutaneous (Abd Sc), Omental (Om)), adiposity and T2DM status on both intracellular and systemic PLA2 levels. Serum and AT was taken from lean, (Age: 44.4±6.2 yr; BMI: 22.6±2.1 kg/m2, n=15) overweight (Age: 45.4±12.3 yr; BMI: 27.1±1.6 kg/m2, n=20) obese (49.0±9.1 yr; BMI: 34.5±3.9 kg/m2, n=13) and T2DM subjects (Age: 53.0±6.13 yr; BMI: 43.9±7.0 kg/m2, n=13). The human adipocyte cell line, Chub-S7, was used to assess the effects of oxidized LDL on PLA2 expression. Paired human Abd Sc and Om AT samples highlighted that Lp-PLA2 expression was increased in obesity and highly expressed in Abd Sc AT (P<0.05). cPLA2 mRNA and protein levels increased with obesity in Abd Sc AT (P<0.05) but decreased in Om AT (P<0.01), whereas iPLA2 mRNA levels remained unchanged in obesity or AT depots. In AT taken from T2DM subjects, Lp-PLA2 mRNA was significantly increased in both Abd Sc and Om compared to the non-diabetic group. Serum Lp-PLA2 showed positive correlations with cholesterol, LDL and oxidized LDL in non-diabetic and T2DM subjects. In vitro, Chub-S7 cells treated with oxidized LDL led to an acute transcriptional activation of Lp-PLA2 (P<0.05). The adipocyte is an active source of Lp-PLA2, increased in obesity and T2DM status and altered in an abdominal depot specific manner. Furthermore, in obesity and T2DM circulating sPLA2 is influenced by lipids. Taken together, the adipocyte represents an active site of LP-PLA2 activity which is altered in an insulin resistant state, affecting both lipid metabolism and the inflammatory response.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.