81.    Lipoprotein lipase activity is enhanced in epicardial adipose tissue from diabetic                patients 

Obesity and its associated co-morbidities, such as Type-2 Diabetes Mellitus (T2DM) are increasing worldwide, together with an increased risk of cardiovascular diseases (CVD). Epicardial Adipose tissue (EAT) is a visceral adipose tissue, which surrounds and infiltrates myocardium and coronary arteries. It has been demonstrated than EAT expansion is associated to an increased risk of CVD. Lipoprotein Lipase (LPL) is the major enzyme involved in triglycerides (TG) hydrolysis from circulating TG-rich lipoproteins (Chylomicrons and VLDLs), supplying fatty acids to AT and contributing to its expansion. This enzyme is highly regulated at both transcriptional (PPARs receptors) and post-translational (Angiopoietin-like proteins, ANGPTLs) levels. It is known that EAT volume is higher in T2DM patients compared to No T2DM patients, although there are no reports about LPL activity in this tissue, and the possible contribution to its expansion. In this context, our aim was to evaluate LPL activity in EAT from T2DM and No T2DM patients. We also studied PPARγ and ANGPTL4 expression, and EAT LPL contribution to circulating VLDL characteristics. Materials and Methods: we studied 43 patients with coronary artery disease, undergoing by-pass graft, divided into two groups: T2DM group (n=16) and No T2DM group (n=27). Anthropometric measures and serum metabolic profile were assessed before surgery, TG/HDL-cholesterol index was calculated to asses Insulin Resistance (IR). During surgery, EAT and Subcutaneous AT (SAT) were obtained. LPL activity was evaluated by a radiometric assay, and regulators expression was determined by western blot. Circulating VLDL were isolated by ultracetrifugation, and characterized in lipid and protein content. Results: Glucose was higher in T2DM patients (p=0.03), without differences in lipoprotein profile between groups. EAT LPL activity was higher in T2DM than in No T2DM (p=0.05), even after adjusting for metformin treatment, and it was negatively associated to TG levels (r=-0.446, p=0.01) and TG/HDL-chol index (r=-0.590, p=0.001), without differences in SAT LPL activity. In both groups, LPL activity was higher in EAT than in SAT (p<0.001). PPARγ expression was higher in EAT from T2DM (p=0.05), without differences in ANGPTL4 expression between groups in any of the studied tissues, and EAT LPL activity was directly associated to PPARγ expression (r=0.666, p=0.001) and negatively associated to ANGPTL4 expression (r=-0.652, p=0.01). No differences were observed in VLDL composition between diabetic and non diabetic patients, while EAT LPL activity was inversely associated to VLDL TG content (r=-0.442, p=0.05). Conclusions: in T2DM patients LPL activity would be regulated at both transcriptional and post-translational level. The increase in LPL activity together with an increase in PPARγ expression could be responsible of the increased EAT volume reported in T2DM patients, partly through the fatty acids released from circulating VLDL.