Li Manna, Qian Ming, Xu Jian
Department of Medicine, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Front Cardiovasc Med. 2017 Aug 9;4:51. doi: 10.3389/fcvm.2017.00051. eCollection 2017.
Obesity is a worldwide epidemic that predisposes individuals to metabolic complications, such as type 2 diabetes mellitus and non-alcoholic fatty liver disease, all of which are related to an imbalance between food intake and energy expenditure. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are urgently needed. A well-accepted paradigm is that crosstalk between organs/tissues contributes to diseases. Endothelial dysfunction characterizes metabolic disorders and the related vascular complications. Over the past two decades, overwhelming studies have focused on mechanisms that lead to endothelial dysfunction. New investigations, however, have begun to appreciate the opposite direction of the crosstalk: endothelial regulation of metabolism, although the underlying mechanisms remain to be elucidated. This review summarizes the evidence that supports the concept of endothelial regulation of obesity and the associated insulin resistance in fat, liver, and skeletal muscles, the classic targets of insulin. Outstanding questions and future research directions are highlighted. Identification of the mechanisms of vascular endothelial regulation of metabolism may offer strategies for prevention and treatment of obesity and the related metabolic complications.
肥胖是一种全球性的流行病，它使个体易患代谢并发症，如2型糖尿病和非酒精性脂肪性肝病，所有这些都与食物摄入和能量消耗之间的失衡有关。迫切需要确定致病分子机制和有效的治疗方法。一个被广泛接受的范例是器官/组织之间的相互作用导致疾病。内皮功能障碍是代谢紊乱及相关血管并发症的特征。在过去二十年中，大量研究集中在导致内皮功能障碍的机制上。然而，新的研究开始认识到这种相互作用的相反方向：内皮对代谢的调节，尽管其潜在机制仍有待阐明。本综述总结了支持内皮调节肥胖以及脂肪、肝脏和骨骼肌（胰岛素的经典作用靶点）中相关胰岛素抵抗这一概念的证据。突出了悬而未决的问题和未来的研究方向。确定血管内皮调节代谢的机制可能为肥胖及相关代谢并发症的预防和治疗提供策略。
