Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPAR alpha/gamma activity in microvascular endothelial cells

Microvascular dysfunction occurs in insulin resistance and/or hyper-insulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPAR alpha/gamma-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), +/- different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10(-8) and 10(-7) M) time-dependently increased Dil-oxLDL uptake and CD36 surface expression (by 30 +/- 13%, p= 24 hour exposure to 50 mu M DHA or EPA, but not other FA, blunted both the constitutive (by 23 +/- 3% and 29 +/- 2%, respectively, p