Lipocalin-2 mediates linoleic acid-induced endothelial dysfunction

Abstract

Lipocalin-2, a 25kDa glycoprotein secreted by adipocytes, mediates endothelial dysfunction induced by dietary obesity in mice. The mechanisms underlying the deteriorating effect of lipocalin-2 on endothelial function are not fully understood. The present experiments were designed to explore the role of lipocalin- 2 in endothelial dysfunction caused by fatty acids. Wild type (WT) and lipocalin-2 knock-out (LKO) mice fed with standard chow were injected intraperitoneally with lipocalin-2, alone or in combination with palmitic, oleic or linoleic acid. Carotid arteries were collected to measure endothelium-dependent contractions (EDC) to increasing concentrations of acetylcholine (in the presence of L-NAME). In WT mice, EDC were enhanced significantly by linoleic, but not palmitic or oleic acid, and/or lipocalin-2. On the other hand, LKO mice were irresponsive to either linoleic acid or lipocalin-2 given alone. However, combined administration of linoleic acid andlipocalin-2 in LKO mice resulted in EDC of similar magnitude as in WT mice treated with the combination. Thus, lipocalin-2 permits the deteriorating effect of linoleic acid on endothelial function.