Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):91-101. doi: 10.1016/j.plefa.2012.07.006. Epub 2012 Aug 29.
Disturbed lipid metabolism has been reported in antiretroviral-naive HIV-1-infected patients suggesting a direct effect of the virus on lipid metabolism. To test that the HIV-1 virus alone could alter lipid concentrations, we measured these concentrations in an HIV-1 transgenic (Tg) rat model of human HIV-1 infection, which demonstrates peripheral and central pathology by 7-9 months of age. Concentrations were measured in high-energy microwaved heart, brain and liver from 7-9 month-old HIV-1 Tg and wildtype rats, and in plasma from non-microwaved rats. Plasma triglycerides and liver cholesteryl ester and total cholesterol concentrations were significantly higher in HIV-1 Tg rats than controls. Heart and plasma fatty acid concentrations reflected concentration differences in liver, which showed higher n-3 and n-6 polyunsaturated fatty acid (PUFA) concentrations in multiple lipid compartments. Fatty acid concentrations were increased or decreased in heart and liver phospholipid subfractions. Brain fatty acid concentrations differed significantly between the groups for minor fatty acids such as linoleic acid and n-3 docosapentaenoic acid. The profound changes in heart, plasma and liver lipid concentrations suggest a direct effect of chronic exposure to the HIV-1 virus on peripheral lipid (including PUFA) metabolism.
研究发现,未接受过抗逆转录病毒治疗的 HIV-1 感染者存在脂质代谢紊乱,提示病毒可能直接影响脂质代谢。为了验证 HIV-1 病毒本身是否可以改变脂质浓度,我们在感染人类 HIV-1 的 HIV-1 转基因(Tg)大鼠模型中测量了这些浓度,该模型在 7-9 月龄时表现出外周和中枢病理学。我们测量了 7-9 月龄 HIV-1 Tg 大鼠和野生型大鼠的微波高能心脏、大脑和肝脏中的浓度,以及非微波大鼠的血浆浓度。与对照组相比,HIV-1 Tg 大鼠的血浆甘油三酯和肝胆固醇酯及总胆固醇浓度显著升高。心脏和血浆脂肪酸浓度反映了肝脏中的浓度差异,肝脏中 n-3 和 n-6 多不饱和脂肪酸(PUFA)在多个脂质区室中的浓度更高。脂肪酸浓度在心脏和肝脏磷脂亚组分中增加或减少。大脑脂肪酸浓度在亚油酸和 n-3 二十二碳五烯酸等微量脂肪酸方面在两组之间存在显著差异。心脏、血浆和肝脏脂质浓度的显著变化表明,慢性接触 HIV-1 病毒会直接影响外周脂质(包括 PUFA)代谢。