Dyslipidemia in visceral obesity: mechanisms, implications, and therapy.
Dyslipidemia in visceral obesity: mechanisms, implications, and therapy.
复制标题
DOI：
10.2165/00129784-200404040-00004
复制
发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Watts, Gerald F
中科院分区：
文献类型：
--
作者：
Chan, Dick C;Barrett, Hugh P R;Watts, Gerald F
内脏肥胖常与高甘油三酯和低血浆高密度脂蛋白胆固醇(HDL-C)以及高浓度的载脂蛋白B(ApoB)相关。这些患者中致动脉粥样硬化的血脂异常可能是由于极低密度脂蛋白(VLDL)apoB-100的过度产生、含有apoB的颗粒分解代谢减少和高密度脂蛋白-apoA-I颗粒分解代谢增加所致。这些异常可能是胰岛素抵抗的全球代谢效应的结果。减轻体重、增加体力活动和适量饮酒是改善内脏肥胖患者血脂异常的一线治疗方法。这些生活方式的改变能有效降低血浆甘油三酯和低密度脂蛋白胆固醇(LDL-C)，升高高密度脂蛋白-C。动力学研究表明，在内脏肥胖中，体重减轻减少了VLDL-apoB的分泌，并反过来上调了LDL-apoB的分解代谢，这可能是由于内脏脂肪质量减少，胰岛素敏感性增强和肝脏脂肪生成减少所致。辅助药物治疗，如HMG-CoA还原酶抑制剂、纤维酸衍生物、烟酸(烟酸)或鱼油，可能经常需要进一步纠正血脂异常。内脏肥胖症的脂类和脂蛋白谱可通过几种作用机制得到改善，包括apoB分泌减少和分解代谢增加，以及apoA-I分泌增加和分解代谢减少。临床试验已经提供了证据支持使用HMG-CoA还原酶抑制剂和纤维酸衍生物来治疗内脏肥胖、胰岛素抵抗和2型糖尿病患者的血脂异常。由于药物单一治疗可能不能充分改善血脂异常，可能需要双重药物治疗，如HMG-CoA还原酶抑制剂/纤维酸衍生物，HMG-CoA还原酶抑制剂/烟酸和HMG-CoA还原酶抑制剂/鱼油组合。新的治疗方法，如胆固醇吸收抑制剂、胆固醇酯转移蛋白拮抗剂和胰岛素增敏剂，也可以单独使用或与其他药物联合使用，以优化治疗。纠正内脏肥胖症和代谢综合征中的血脂异常的多种方法的基础依赖于了解个别治疗成分的作用机制。
Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.