Kang Yu Mi, Kim Francis, Lee Woo Je
Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Medicine, Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA, USA.
Diabetes Metab J. 2017 Apr;41(2):89-95. doi: 10.4093/dmj.2017.41.2.89.
Obesity has quickly become a worldwide pandemic, causing major adverse health outcomes such as dyslipidemia, type 2 diabetes mellitus, cardiovascular disease and cancers. Obesity-induced insulin resistance is the key for developing these metabolic disorders, and investigation to understand the molecular mechanisms involved has been vibrant for the past few decades. Of these, low-grade chronic inflammation is suggested as a critical concept in the development of obesity-induced insulin resistance, and the anti-inflammatory effect of nitric oxide (NO) signaling has been reported to be linked to improvement of insulin resistance in multiple organs involved in glucose metabolism. Recently, a body of evidence suggested that vasodilatory-stimulated phosphoprotein (VASP), a downstream mediator of NO signaling plays a crucial role in the anti-inflammatory effect and improvement of peripheral insulin resistance. These preclinical studies suggest that NO/VASP signaling could be an ideal therapeutic target in the treatment of obesity-related metabolic dysfunction. In this review, we introduce studies that investigated the protective role of NO/VASP signaling against obesity-related inflammation and insulin resistance in various tissues.
肥胖已迅速成为一种全球流行病，导致血脂异常、2型糖尿病、心血管疾病和癌症等主要不良健康后果。肥胖诱导的胰岛素抵抗是引发这些代谢紊乱的关键因素，在过去几十年里，对于了解其中涉及的分子机制的研究一直十分活跃。其中，低度慢性炎症被认为是肥胖诱导的胰岛素抵抗发展过程中的一个关键概念，并且有报道称一氧化氮（NO）信号的抗炎作用与改善参与葡萄糖代谢的多个器官的胰岛素抵抗有关。最近，大量证据表明，作为NO信号下游介质的血管舒张刺激磷蛋白（VASP）在抗炎作用和改善外周胰岛素抵抗方面起着关键作用。这些临床前研究表明，NO/VASP信号可能是治疗肥胖相关代谢功能障碍的理想治疗靶点。在这篇综述中，我们介绍了一些研究，这些研究探讨了NO/VASP信号在各种组织中对肥胖相关炎症和胰岛素抵抗的保护作用。
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