Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
Curr Pharm Des. 2014;20(4):652-8. doi: 10.2174/138161282004140213160930.
Obesity and metabolic syndrome are one of the most devastating risk factors for cardiovascular diseases. The obesity gene product leptin plays a central role in the regulation of food intake and energy expenditure. The physiological and pathophysiological roles of leptin in cardiovascular system have been investigated extensively since its discovery in 1994. In addition to its well-established metabolic effects, more recent evidence have depicted a rather pivotal role of leptin in inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis and tissue remodeling en route to the pathogenesis of type 2 diabetes mellitus, hypertension, atherosclerosis, and insulin resistance. Under physiological condition, leptin is known to reduce appetite, promote energy expenditure, increase sympathetic activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin may regulate cardiac and vascular function through a nitric oxide-dependent mechanism. However, hyperleptinemia usually occurs with progressively increased body weight and metabolic syndrome development, leading to a state of global or selective leptin resistance. Both central and peripheral leptin resistance may be present under pathophysiological conditions such as inflammation, insulin resistance, hyperlipidemia and a cadre of other cardiovascular diseases including hypertension, atherosclerosis, obesity, ischemic heart disease and heart failure. In this review, we will discuss cardiovascular actions of leptin related to various components of metabolic syndrome. Particular emphasis will be given to insights derived from therapeutic interventions with lifestyle modification, cardiovascular drugs, anti-diabetic and anti-obesity drugs.
肥胖和代谢综合征是心血管疾病最具破坏性的危险因素之一。肥胖基因产物瘦素在调节食物摄入和能量消耗方面起着核心作用。自 1994 年发现瘦素以来，人们已经广泛研究了它在心血管系统中的生理和病理生理作用。除了其公认的代谢作用外，最近的证据还描绘了瘦素在炎症、氧化应激、内质网应激、细胞凋亡和组织重塑中发挥着至关重要的作用，从而导致 2 型糖尿病、高血压、动脉粥样硬化和胰岛素抵抗的发病机制。在生理条件下，瘦素已知可降低食欲、促进能量消耗、增加交感神经活动、促进葡萄糖利用和改善胰岛素敏感性。此外，瘦素可能通过依赖一氧化氮的机制调节心脏和血管功能。然而，随着体重逐渐增加和代谢综合征的发展，通常会出现高瘦素血症，导致全身或选择性瘦素抵抗。在炎症、胰岛素抵抗、高血脂和一系列其他心血管疾病（包括高血压、动脉粥样硬化、肥胖、缺血性心脏病和心力衰竭）等病理生理条件下，可能存在中枢和外周瘦素抵抗。在本文中，我们将讨论与代谢综合征各组成部分相关的瘦素的心血管作用。特别强调的是，将从生活方式改变、心血管药物、抗糖尿病和抗肥胖药物的治疗干预中获得的见解。
