Watts Gerald F, Ooi Esther M M, Chan Dick C
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Pharmacol Ther. 2009 Sep;123(3):281-91. doi: 10.1016/j.pharmthera.2009.04.005. Epub 2009 May 31.
Elevated apolipoprotein (apo) B-100 is a common abnormality in insulin-resistant subjects with obesity and type 2 diabetes mellitus that increases risk of cardiovascular disease. ApoB-100 metabolism is complex. Kinetic studies using stable isotope tracer have provided useful mechanistic insight into its therapeutic regulation. Dysregulation of apoB-100 metabolism is integral to dyslipidaemia in the metabolic syndrome (MetS). This is dynamically related to a combination of overproduction of very-low density lipoprotein apoB-100 and decreased catabolism of apoB-containing particles, with accelerated catabolism of high-density lipoprotein (HDL) particles. These abnormalities may be consequent on a global effect of insulin resistance and accumulation of visceral and liver fat. Several therapeutic interventions, such as weight loss, physical exercise, statins, fibrates, fish oils and cholesteryl ester transfer protein inhibitors can correct apoB-100 metabolism in MetS. This encapsulates several kinetic mechanisms of action, including decreased secretion of apoB-100, increased catabolism of apoB-100 and delayed catabolism of HDL particles. Other agents, including cholesterol absorption inhibitors, niacins, and endocannabinoid-1 receptor blockers, have also been shown to improve plasma lipid and lipoprotein abnormalities in insulin resistance; their mechanisms of action require further investigation in MetS. The complementary mechanisms of action of different therapies support the use of combination regimens to treat dyslipoproteinaemia in MetS, including type 2 diabetes. Tracer methodology is a powerful tool to evaluate established and new lipid-regulating therapies.
载脂蛋白（apo）B - 100升高在伴有肥胖和2型糖尿病的胰岛素抵抗患者中是一种常见异常，会增加心血管疾病风险。ApoB - 100的代谢很复杂。使用稳定同位素示踪剂的动力学研究为其治疗调控提供了有用的机制性见解。ApoB - 100代谢失调是代谢综合征（MetS）血脂异常的一个组成部分。这与极低密度脂蛋白apoB - 100的过度产生以及含apoB颗粒的分解代谢减少，同时高密度脂蛋白（HDL）颗粒分解代谢加速的综合情况动态相关。这些异常可能是胰岛素抵抗以及内脏和肝脏脂肪堆积的整体效应所致。几种治疗干预措施，如减肥、体育锻炼、他汀类药物、贝特类药物、鱼油和胆固醇酯转运蛋白抑制剂，可以纠正MetS中的apoB - 100代谢。这涵盖了几种动力学作用机制，包括apoB - 100分泌减少、apoB - 100分解代谢增加以及HDL颗粒分解代谢延迟。其他药物，包括胆固醇吸收抑制剂、烟酸和内源性大麻素 - 1受体阻滞剂，也已被证明可改善胰岛素抵抗中的血脂和脂蛋白异常；它们在MetS中的作用机制需要进一步研究。不同疗法的互补作用机制支持使用联合方案来治疗MetS（包括2型糖尿病）中的血脂蛋白异常。示踪方法是评估已确立和新的脂质调节疗法的有力工具。
