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. Supported by the Hong Kong Research Grant Council