Effects of fatty acids on the growth of beta‐cells and on albumin‐mediated cholesterol effflux from endothelial cells

Abstract

There is mounting evidence that free fatty acids (FFAs) plays a role in the pathogenesis of diabetes and cardiovascular diseases. However, the effects of human serum albumin (HSA)/FFA complexes on ß‐cells as well as on HSA‐mediated cholesterol efflux are not well known. Thus, we exposed the insulinoma ß‐cells, HIT‐TI5 to different HSA/FFAs complexes for 24hrs followed by assessment of insulin secretion and cell viability. Also, a human endothelial cell line, EA.hy926 was used as the model system to study cholesterol efflux. In the presence of HSA, palmitate and stearate induced significant cell death at 0.1mM or higher, which was not significantly inhibited by the two apoptosis inhibitors, cyclosporin A and ZVAD‐FMK. In contrast, myristate, palmitoleate, oleate, and elaidate bound to HSA showed minimal effects on cell viability. Additionally, insulin secretion was significantly reduced by HSA/oleate complexes. We also found differential effects on cell viability by HSA mutants/FFAs complexes. For efflux studies, HSA complexed to oleate or palmitate at 1:5.3 molar ratios showed significant reduction in cholesterol efflux but not with arachidonate. In summary, this study showed that FFA‐induced changes of cellular functions are dependent upon the types and concentrations of FFAs which might be modified by HSA variants.[Funding: Hawaii EXPORT Centre, HCF, and an award from the American Heart Association].