Omentin-1: Protective impact on ischemic stroke via ameliorating atherosclerosis

•Omentin-1 serves as a novel biomarker for predicting the functional outcome of acute ischemic stroke, and low circulating omentin-1 level indicates high risk of ischemic stroke.•Elevated omentin-1 level could attenuate atherosclerosis and exert a favorable impact on cerebral ischemia.•Omentin-1 has benefical effects on vascular inflammation and dysfunction through various signaling pathways.•Metformin and statins together with omentin-1 have great potential to be developed into novel drug therapy against ischemic stroke. Omentin-1, a newly identified adipokine, has recently been revealed as a novel biomarker for ischemic stroke (IS). Low circulating omentin-1 levels could indicate a high risk of IS, and elevated omentin-1 levels exert a favorable impact on cerebral ischemia. Furthermore, omentin-1 has anti-atherosclerotic, anti-inflammatory, and cardiovascular protective capabilities through the intracellular Akt/AMP-activated protein kinase (AMPK)/ nuclear factor-κB (NF-κB) and certain protein kinase (ERK, JNK, and p38) signaling pathways. Omentin-1 also alleviates endothelial cell dysfunction, improves revascularization via the Akt-endothelial nitric-oxide synthase (eNOS) regulatory axis, promotes endothelium-dependent vasodilation through endothelium-derived NO in an eNOS fashion, and inhibits VSMC proliferation by means of AMPK/ERK signaling pathways, VSMC migration via inactivation of the NADPH oxidase (NOX)/ROS/p38/HSP27 pathways and artery calcification via the PI3K-Akt pathway. These findings indicate that omentin-1 may be a negative mediator of IS. Pharmacologically, several lines of clinical evidence indicate that metformin and statins could elevate omentin-1 levels, although the specific mechanism has not been precisely delineated until now. This study is the first to summarize the comprehensive mechanisms between omentin-1 and atherosclerosis and to review the shielding effect of omentin-1 on IS. We shed light on omentin-1 as a novel therapeutic target for combating IS.