MECH OF HIGHLY ACTIVE ANTI-RETROVIRAL THERAPY-INDUCED HYPERLIPIDEMIA IN HIV

HIV 高活性抗逆转录病毒治疗引起的高脂血症的机制

• 批准号: 7355160
• 负责人: A Carpentier
• 金额: $ 0.7万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355160
• 关键词: MECH; HIGHLY; ACTIVE; ANTI; RETROVIRAL

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of highly active anti-retroviral therapy (HAART) is associated with long-term adverse metabolic events including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of the present study was to prospectively examine the mechanism of HAART-induced hyperlipidemia in HIV-seropositive, HAART-na¿ve men prior to the development of frank lipodystrophy. Patient's (n = 13) weight, BMI, lean mass, and percent fat mass, waist circumference did not change after 8 weeks of treatment with HAART. Plasma FFA concentration was already elevated in HAART-na¿ve patients compared to healthy, untreated, HIV negative control individuals and was further increased after 8 weeks of HAART in the former. Insulin-mediated suppression of plasma FFA concentrations was impaired both prior to and following introduction of HAART, compared to healthy, matched controls. VLDL-apoB and VLDL-TG concentrations rose significantly from normal levels after HAART. Compared to healthy control subjects, VLDL fractional catabolic rate and clearance in HIV-seropositive individuals was reduced by approximately 40%, a defect that was not corrected after HAART. The increase in VLDL after HAART was explained by an increase of VLDL-apoB and VLDL-TG secretion towards normal while the impaired VLDL clearance remained unchanged. We conclude that elevation of circulating VLDL early in the course of HAART is caused by the combination of impaired VLDL clearance already present in HAART-na¿ve HIV-seropositive patients and HAART-mediated increase in VLDL secretion. These changes occur concomitantly with an elevation of plasma free fatty acids but before significant change in body composition.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。高效抗逆转录病毒治疗（HAART）的使用与长期不良代谢事件相关，包括脂肪代谢障碍、血脂异常和胰岛素抵抗。本研究的目的是前瞻性地研究HAART诱导的高脂血症的机制，在HIV血清阳性，HAART初治男性发展坦率的脂肪营养不良之前。HAART治疗8周后，患者（n = 13）的体重、BMI、瘦体重和脂肪量百分比、腰围没有变化。与健康、未经治疗的HIV阴性对照个体相比，HAART初治患者的血浆FFA浓度已经升高，并且在HAART治疗8周后进一步升高。胰岛素介导的抑制血浆FFA浓度受损之前和之后引入HAART，相比健康，匹配的对照。HAART后VLDL-apoB和VLDL-TG浓度较正常水平显著升高。与健康对照受试者相比，HIV血清阳性个体的VLDL分解代谢率和清除率降低了约40%，HAART后未纠正这一缺陷。HAART后VLDL增加的原因是VLDL-apoB和VLDL-TG分泌向正常水平增加，而受损的VLDL清除率保持不变。我们的结论是，HAART过程早期循环VLDL的升高是由HAART初治HIV血清阳性患者中已经存在的VLDL清除受损和HAART介导的VLDL分泌增加共同引起的。这些变化伴随着血浆游离脂肪酸的升高而发生，但在身体成分发生显著变化之前。