Martin Seth S, Qasim Atif, Reilly Muredach P
Department of Medicine, Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6160, USA.
J Am Coll Cardiol. 2008 Oct 7;52(15):1201-10. doi: 10.1016/j.jacc.2008.05.060.
Leptin is an adipocyte-derived hormone and cytokine that regulates energy balance through a wide range of functions, including several that are important to cardiovascular health. Increased circulating leptin, a marker of leptin resistance, is common in obesity and independently associated with insulin resistance and cardiovascular disease (CVD) in humans. The mechanisms of leptin resistance include genetic mutation, leptin self-regulation, limited tissue access, and cellular or circulating molecular regulation. Evidence suggests that central leptin resistance causes obesity and that obesity-induced leptin resistance injures numerous peripheral tissues, including liver, pancreas, platelets, vasculature, and myocardium. This metabolic- and inflammatory-mediated injury may result from either resistance to leptin's action in selective tissues, or excess leptin action from adiposity-associated hyperleptinemia. In this sense, the term "leptin resistance" encompasses a complex pathophysiological phenomenon. The leptin axis has functional interactions with elements of metabolism, such as insulin, and inflammation, including mediators of innate immunity, such as interleukin-6. Leptin is even purported to physically interact with C-reactive protein, resulting in leptin resistance, which is particularly intriguing, given C-reactive protein's well-studied relationship to cardiovascular disease. Given that plasma levels of leptin and inflammatory markers are correlated and also predict cardiovascular risk, it is conceivable that part of this risk may be mediated through leptin resistance-related insulin resistance, chronic inflammation, type II diabetes, hypertension, atherothrombosis, and myocardial injury. Leptin resistance and its interactions with metabolic and inflammatory factors, therefore, represent potential novel diagnostic and therapeutic targets in obesity-related cardiovascular disease.
瘦素是一种由脂肪细胞分泌的激素和细胞因子，它通过多种功能调节能量平衡，其中包括对心血管健康至关重要的一些功能。循环瘦素水平升高是瘦素抵抗的一个标志，在肥胖人群中很常见，并且与人类的胰岛素抵抗和心血管疾病（CVD）独立相关。瘦素抵抗的机制包括基因突变、瘦素的自我调节、组织接触受限以及细胞或循环分子调节。有证据表明，中枢性瘦素抵抗会导致肥胖，而肥胖诱导的瘦素抵抗会损害许多外周组织，包括肝脏、胰腺、血小板、血管和心肌。这种由代谢和炎症介导的损伤可能是由于选择性组织对瘦素作用的抵抗，或者是肥胖相关的高瘦素血症导致的瘦素作用过度。从这个意义上说，“瘦素抵抗”一词涵盖了一种复杂的病理生理现象。瘦素轴与代谢元素（如胰岛素）以及炎症（包括先天免疫介质，如白细胞介素-6）存在功能相互作用。甚至有人认为瘦素与C反应蛋白存在物理相互作用，从而导致瘦素抵抗，考虑到C反应蛋白与心血管疾病的关系已得到充分研究，这一点尤其引人关注。鉴于瘦素和炎症标志物的血浆水平相关，并且也能预测心血管风险，可以想象这种风险的一部分可能是通过与瘦素抵抗相关的胰岛素抵抗、慢性炎症、II型糖尿病、高血压、动脉粥样血栓形成和心肌损伤介导的。因此，瘦素抵抗及其与代谢和炎症因子的相互作用代表了肥胖相关心血管疾病潜在的新型诊断和治疗靶点。
