Ooi Esther M M, Barrett P Hugh R, Chan Dick C, Watts Gerald F
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia.
Clin Sci (Lond). 2008 May;114(10):611-24. doi: 10.1042/CS20070308.
The concurrence of visceral obesity, insulin resistance and dyslipidaemia comprises the concept of the metabolic syndrome. The metabolic syndrome is an escalating problem in developed and developing societies that tracks with the obesity epidemic. Dyslipidaemia in the metabolic syndrome is potently atherogenic and, hence, is a major risk factor for CVD (cardiovascular disease) in these subjects. It is globally characterized by hypertriglyceridaemia, near normal LDL (low-density lipoprotein)-cholesterol and low plasma HDL (high-density lipoprotein)-cholesterol. ApoC-III (apolipoprotein C-III), an important regulator of lipoprotein metabolism, is strongly associated with hypertriglyceridaemia and the progression of CVD. ApoC-III impairs the lipolysis of TRLs [triacylglycerol (triglyceride)-rich lipoproteins] by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. In the circulation, apoC-III is associated with TRLs and HDL, and freely exchanges among these lipoprotein particle systems. However, to fully understand the complex physiology and pathophysiology requires the application of tracer methodology and mathematical modelling. In addition, experimental evidence shows that apoC-III may also have a direct role in atherosclerosis. In the metabolic syndrome, increased apoC-III concentration, resulting from hepatic overproduction of VLDL (very-LDL) apoC-III, is strongly associated with delayed catabolism of triacylglycerols and TRLs. Several therapies pertinent to the metabolic syndrome, such as PPAR (peroxisome-proliferator-activated receptor) agonists and statins, can regulate apoC-III transport in the metabolic syndrome. Regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidaemia and CVD risk in the metabolic syndrome.
内脏肥胖、胰岛素抵抗和血脂异常并存构成了代谢综合征的概念。在发达国家和发展中国家，代谢综合征是一个日益严重的问题，与肥胖流行密切相关。代谢综合征中的血脂异常具有很强的致动脉粥样硬化作用，因此是这些患者发生心血管疾病（CVD）的主要危险因素。其全球特征是高甘油三酯血症、低密度脂蛋白（LDL）胆固醇接近正常以及血浆高密度脂蛋白（HDL）胆固醇降低。载脂蛋白C-III（ApoC-III）是脂蛋白代谢的重要调节因子，与高甘油三酯血症和心血管疾病的进展密切相关。ApoC-III通过抑制脂蛋白脂肪酶损害富含三酰甘油（甘油三酯）的脂蛋白（TRL）的脂解作用，并通过残粒受体抑制肝脏对TRL的摄取。在循环中，ApoC-III与TRL和HDL相关，并在这些脂蛋白颗粒系统之间自由交换。然而，要全面了解复杂的生理和病理生理过程需要应用示踪方法和数学建模。此外，实验证据表明ApoC-III在动脉粥样硬化中可能也有直接作用。在代谢综合征中，由于肝脏极低密度脂蛋白（VLDL）ApoC-III过度产生导致ApoC-III浓度升高，与三酰甘油和TRL的分解代谢延迟密切相关。几种与代谢综合征相关的治疗方法，如过氧化物酶体增殖物激活受体（PPAR）激动剂和他汀类药物，可以调节代谢综合征中ApoC-III的转运。调节ApoC-III代谢可能是管理代谢综合征中血脂异常和心血管疾病风险的一种重要的新治疗方法。
