Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
School of Biomedical Sciences, Kent State University, Kent, OH 44240, USA.
Int J Mol Sci. 2021 May 21;22(11):5446. doi: 10.3390/ijms22115446.
Increasing adipose tissue mass in obesity directly correlates with elevated circulating leptin levels. Leptin is an adipokine known to play a role in numerous biological processes including regulation of energy homeostasis, inflammation, vascular function and angiogenesis. While physiological concentrations of leptin may exhibit multiple beneficial effects, chronically elevated pathophysiological levels or hyperleptinemia, characteristic of obesity and diabetes, is a major risk factor for development of atherosclerosis. Hyperleptinemia results in a state of selective leptin resistance such that while beneficial metabolic effects of leptin are dampened, deleterious vascular effects of leptin are conserved attributing to vascular dysfunction. Leptin exerts potent proatherogenic effects on multiple vascular cell types including macrophages, endothelial cells and smooth muscle cells; these effects are mediated via an interaction of leptin with the long form of leptin receptor, abundantly expressed in atherosclerotic plaques. This review provides a summary of recent in vivo and in vitro studies that highlight a role of leptin in the pathogenesis of atherosclerotic complications associated with obesity and diabetes.
肥胖症中脂肪组织质量的增加与循环中瘦素水平的升高直接相关。瘦素是一种脂肪细胞因子，已知在许多生物学过程中发挥作用，包括能量稳态调节、炎症、血管功能和血管生成。虽然瘦素的生理浓度可能表现出多种有益的作用，但肥胖症和糖尿病特征性的慢性升高的病理生理水平或高瘦素血症是动脉粥样硬化发展的主要危险因素。高瘦素血症导致选择性瘦素抵抗，从而削弱了瘦素的有益代谢作用，而保留了瘦素的有害血管作用，导致血管功能障碍。瘦素对包括巨噬细胞、内皮细胞和平滑肌细胞在内的多种血管细胞类型产生强烈的促动脉粥样硬化作用；这些作用是通过瘦素与在动脉粥样硬化斑块中大量表达的瘦素受体的长形式相互作用介导的。本综述提供了最近的体内和体外研究的总结，这些研究强调了瘦素在与肥胖和糖尿病相关的动脉粥样硬化并发症发病机制中的作用。
