Lipocalin‐2 deficiency prevents hypertension in dietary obese mice

Abstract

Objectives Lipocalin-2 is a pro-inflammatory adipokine up-regulated in obese animals and human subjects. Mice without lipocalin-2 (LKO) are protected from dietary or genetic obesity-induced metabolic dysfunctions and vascular abnormalities. The present study aimed to investigate the role of lipocalin-2 and the mechanisms underlying its actions in dietary obesity-induced hypertension. Methods Wild-type (WT) and LKO, as well as mice with tissue-specific deletion of lipocalin-2 were subjected to 20-weeks high-fat diet treatment. Blood pressure was monitored with implantable radio telemetry. Wire myography was performed to evaluate the vascular responses in mesenteric arteries without or with the attached perivascular adipose tissue (PVAT). Enzyme-linked immunosorbent assay (ELISA), Western blotting and quantitative PCR were performed to measure the levels of angiotensin peptides and angiotensin-converting enzymes. Results Deletion of LCN2 alleles prevented the development of hypertension induced by dietary obesity. Lipocalin-2 deficiency inhibited obesity-associated arterial remodeling and promoted the anti-contractile function of PVAT. The data demonstrated that lipocalin-2 was involved in the local production of angiotensin peptides via modulating the expression of angiotensin-converting enzymes. Conclusion Lipocalin-2 plays a causal role in blood pressure elevation. The source of the pathological form of lipocalin-2 contributing to obesity-induced hypertension needs to be further investigated.