IMPACT OF MICRONUTRIENTS OF PROGRESSION OF SIV

微量营养素对 SIV 进展的影响

• 批准号: 7349491
• 负责人: SHERWOOD GORBACH
• 金额: $ 13.48万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7349491
• 关键词: IMPACT; MICRONUTRIENTS; PROGRESSION; SIV

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. Studies in patients with HIV have revealed that serum micronutrient levels are often below normal levels and may cause more rapid progression of HIV-related diseases. Other studies have documented the effects of antiretroviral treatments on changes in body composition, glucose metabolism and lipid metabolism. Intervention trails with micronutrients and single antiretrovirals are difficult to carry out in humans, both practically and ethically. Because the Simian Immunodeficiency Virus (SIV) produces an infection in macaques that is remarkable similar to that caused by HIV in humans, it provides an ideal model to examine the potential benefit of micronutrient supplementation and antiretroviral intervention on progression of SIV infection. In animals receiving antiretroviral therapy on low fat, high fiber chow, there were no significant changes in fasting triglycerides, HDL, LDL, total cholesterol or glucose. However, there was a statistically significant increase in insulin area-under-the ¿curve (p=0.04) and a decrease in adiponectin (p=0.05) and changes in trunk fat approaching significance (p=0.08). A second group of juvenile animals was switched to a high fat, low fiber Western Diet (WD) after inoculation. Two months after switching to the WD, animals began six months of treatment with PMPA (tenofovir). Neither diet change nor introduction of viral control with PMPA produced any significant difference in glucose or insulin area under the curve by IVGTT. The high fat WD diet alone resulted in significant increases in LDL-cholesterol and total cholesterol. However, these lipids did not change further after treatment with PMPA, thus confirming that PMPA itself does not induce changes in lipids. Adult female macaques fed a WD not only displayed significant increases in LDL and total cholesterol, but also had significant decreases in HDL-cholesterol and significant increases in triglycerides, mirroring the lipid profile seen in HIV-infected individuals. Given these results, more studies will be conducted using individual antiretrovirals and diets to examine the effects on lipid metabolism and 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来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。对艾滋病毒感染者的研究表明，血清微量营养素水平往往低于正常水平，可能导致艾滋病毒相关疾病的更快进展。其他研究也记录了抗逆转录病毒治疗对身体组成、葡萄糖代谢和脂质代谢变化的影响。微量营养素和单一抗逆转录病毒药物的干预试验难以在人类中进行，无论是在实践中还是在伦理上。由于猴免疫缺陷病毒（SIV）在猕猴中产生的感染与HIV在人类中引起的感染非常相似，因此它提供了一个理想的模型来检查微量营养素补充和抗逆转录病毒干预对SIV感染进展的潜在益处。在接受抗逆转录病毒治疗的低脂肪、高纤维食物的动物中，空腹甘油三酯、高密度脂蛋白、低密度脂蛋白、总胆固醇或葡萄糖没有显著变化。然而，胰岛素曲线下面积有统计学显著性增加（p=0.04），脂联素减少（p=0.05），躯干脂肪变化接近显著性（p=0.08）。接种后，将第二组幼龄动物转换为高脂肪、低纤维的西方饮食（WD）。在切换到WD两个月后，动物开始用PMPA（替诺福韦）治疗六个月。无论是饮食改变还是引入PMPA病毒控制，IVGTT测得的葡萄糖或胰岛素曲线下面积均未产生任何显著差异。单独的高脂肪WD饮食导致LDL-胆固醇和总胆固醇显著增加。然而，这些脂质在用PMPA处理后没有进一步变化，从而证实PMPA本身不诱导脂质变化。喂饲WD的成年雌性猕猴不仅表现出LDL和总胆固醇的显著增加，而且HDL-胆固醇显著降低，甘油三酯显著增加，反映了HIV感染者的血脂谱。鉴于这些结果，将使用个体抗逆转录病毒药物和饮食进行更多的研究，以检查对脂质代谢和身体成分的影响。