Rashid Shirya, Genest Jacques
Department of Medicine, Division of Cardiology, McGill University, Royal Victoria Hospital, Room H7-13, 687 Pine Avenue West, Montreal, Quebec, Canada H3A 1A1.
Obesity (Silver Spring). 2007 Dec;15(12):2875-88. doi: 10.1038/oby.2007.342.
Reduced levels of high-density lipoproteins (HDL) in non-obese and obese states are associated with increased risk for the development of coronary artery disease. Therefore, it is imperative to determine the mechanisms responsible for reduced HDL in obese states and, conversely, to examine therapies aimed at increasing HDL levels in these individuals. This paper examines the multiple causes for reduced HDL in obese states and the effect of exercise and diet--two non-pharmacologic therapies--on HDL metabolism in humans. In general, the concentration of HDL-cholesterol is adversely altered in obesity, with HDL-cholesterol levels associated with both the degree and distribution of obesity. More specifically, intra-abdominal visceral fat deposition is an important negative correlate of HDL-cholesterol. The specific subfractions of HDL that are altered in obese states include the HDL2, apolipoprotein A-I, and pre-beta1 subfractions. Decreased HDL levels in obesity have been attributed to both an enhancement in the uptake of HDL2 by adipocytes and an increase in the catabolism of apolipoprotein A-I on HDL particles. In addition, there is a decrease in the conversion of the pre-beta1 subfraction, the initial acceptor of cholesterol from peripheral cells, to pre-beta2 particles. Conversely, as a means of reversing the decrease in HDL levels in obesity, sustained weight loss is an effective method. More specifically, weight loss achieved through exercise is more effective at raising HDL levels than dieting. Exercise mediates positive effects on HDL levels at least partly through changes in enzymes of HDL metabolism. Increased lipid transfer to HDL by lipoprotein lipase and reduced HDL clearance by hepatic triglyceride lipase as a result of endurance training are two important mechanisms for increases in HDL observed from exercise.
在非肥胖和肥胖状态下，高密度脂蛋白（HDL）水平降低与冠状动脉疾病发生风险增加相关。因此，必须确定导致肥胖状态下HDL降低的机制，反之，研究旨在提高这些个体HDL水平的治疗方法。本文探讨了肥胖状态下HDL降低的多种原因，以及运动和饮食这两种非药物治疗方法对人体HDL代谢的影响。一般来说，肥胖时HDL胆固醇浓度会发生不利变化，HDL胆固醇水平与肥胖程度及分布均有关联。更具体地说，腹内内脏脂肪沉积是HDL胆固醇的重要负相关因素。肥胖状态下发生改变的HDL特定亚组分包括HDL2、载脂蛋白A-I和前β1亚组分。肥胖时HDL水平降低既归因于脂肪细胞对HDL2摄取的增强，也归因于HDL颗粒上载脂蛋白A-I分解代谢的增加。此外，从外周细胞接受胆固醇的初始受体前β1亚组分向前β2颗粒的转化减少。相反，作为逆转肥胖时HDL水平降低的一种方法，持续体重减轻是一种有效手段。更具体地说，通过运动实现的体重减轻在提高HDL水平方面比节食更有效。运动至少部分通过HDL代谢酶的变化对HDL水平产生积极影响。耐力训练导致脂蛋白脂肪酶向HDL的脂质转运增加以及肝甘油三酯脂肪酶对HDL的清除减少，是运动后观察到HDL增加的两个重要机制。
