Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 31 P188 | DOI: 10.1530/endoabs.31.P188

SFEBES2013 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (67 abstracts)

Human abdominal subcutaneous adipocytes as an active source of LpPLA2, influenced by fat depot and metabolic state, with LpPLA2 converting LDL into more potent atherogenic Ox-LDL, in vitro

Warunee Kumsaiyai 1 , Alison Harte 1 , Fadi Al-Naji 1 , Nasser Al-Daghri 1 , Ioannis Kyrou 1 , Thomas Barber 1, , Shaun Sabico 2 , Gyanendra Tripathi 1 & Philip McTernan 1

1Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK; 2Biomarkers Research Program, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Human Metabolism Research Unit, WISDEM, UHCW, Coventry, UK.

Lipoprotein-associated phospholipase A2 (LpPLA2) is a member of the phospholipaseA2 super family of enzymes, and is upregulated in arterial inflammation, obesity and cardiovascular disease. The other isoforms, iPLA2 and cPLA2, appear to contribute to inflammation through production of lipid mediators. The role of PLA2 in human adipose tissue (AT) is unclear, therefore we sought to i) characterise PLA2 isoforms in lean, obese, T2DM abdominal subcutaneous (AbdSc) and omental (Om) AT ii) evaluate the role of lipids and inflammatory markers on circulating LpPLA2 levels and iii) determine the in vitro regulation of LpPLA2 in human adipocytes.

AT and sera from lean, overweight, obese and T2DM subjects were taken. PLA2 gene expression was determined by microarray, RT-qPCR and Western Blot. Association between circulating LpPLA2 and metabolic parameters were investigated. The human adipocyte cell line, Chub-S7, was used to assess the effects of oxidized LDL on PLA2 expression.

LpPLA2 mRNA levels were higher in AbdSc AT than Om AT in obesity by twofold (P<0.05). The cPLA2 protein expression was increased with obesity in AbdSc AT (P<0.01). T2DM showed increased LpPLA2 mRNA levels in AbdSc (P<0.001) and OmAT (P<0.01). Serum LpPLA2 showed positive correlations with cholesterol, TG, LDL, endotoxin and oxidized LDL (Ox-LDL) (P<0.001) in non-diabetic subjects and with Ox-LDL (P<0.001), LDL (P<0.01) and cholesterol (P<0.05) in T2DM. In differentiated pre-adipocytes, activation of LpPLA2 protein expression was noted in response to LDL and Ox-LDL (P<0.001).

The adipocyte appears to be an active source of LpPLA2, altered by fat depot and metabolic state, with LpPLA2 protein expression being induced by LDL and Ox-LDL in vitro. As such, increased LpPLA2 protein from the adipocyte in obesity and/or T2DM may contribute to raise circulating Ox-LDL, which promotes further inflammation and atherosclerotic risk. Taken together, LpPLA2 in the adipocyte and AT represents an important therapeutic target to reduce inflammation, atherosclerotic risk and development of metabolic complications.

Declaration of funding: Birminggham Science City and Thai Government.

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