Increased de novo hepatic lipogenesis in human immunodeficiency virus infection.
Increased de novo hepatic lipogenesis in human immunodeficiency virus infection.
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DOI：
10.1210/jcem.76.3.8445011
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发表时间：
1993-03
期刊：
影响因子：
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通讯作者：
M. Hellerstein;C. Grunfeld;K. Wu;M. Christiansen;S. Kaempfer;C. Kletke;C. Shackleton
中科院分区：
文献类型：
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作者：
M. Hellerstein;C. Grunfeld;K. Wu;M. Christiansen;S. Kaempfer;C. Kletke;C. Shackleton
我们使用新开发的稳定同位素方法测量了人类免疫缺陷病毒（HIV）感染男性的从头脂肪生成。研究对象包括有体重减轻史的 HIV 感染者（n = 17，平均体重减轻 14.9 +/- 3.2 kg）、CD4 T 细胞计数正常的无症状 HIV 血清阳性受试者（n = 7）和健康 HIV 血清阴性对照（n = 11）。使用最近描述的异生素探针技术和质量同位素分析，通过输注[2-13C]-乙酸盐来测定肝脏脂肪生成。通过高效液相色谱/质谱法测量分泌的磺胺甲恶唑-乙酸盐的肝乙酰辅酶A富集，并通过气相色谱-质谱法测量掺入极低密度脂蛋白-脂肪酸。同时测定循环肿瘤坏死因子（TNF）、白细胞介素-1（IL-1）、干扰素α（IFNα）、胰岛素和甘油三酯，并进行7天称重食物记录。与正常对照相比，体重减轻的 HIV 感染者的从头肝脏脂肪生成增加了 3 至 4 倍（在禁食过夜和进食状态下，棕榈酸盐和硬脂酸盐的 P < 0.05），并且在无症状的 HIV 血清阳性受试者中也显着增加。在任何受试者中都无法测量循环 TNF 和 IL-1（IL-1 的检测限为 2 pg/ml，TNF 的检测限为 20 pg/ml）。在 17 名消瘦受试者中，有 11 名受试者的血清 IFN α 是可测量的，并且在禁食过夜但在进食状态下与脂肪从头生成显着相关。尽管脂肪生成率升高，但无症状 HIV 感染者的血清 IFN α 无法测量。与对照组（0.67 +/- 0.08 mmol/L）相比，体重减轻（2.09 +/- 0.28 mmol/L）和无症状 HIV 阳性受试者（1.34 +/- 0.34 mmol/L）的血清甘油三酯浓度升高，并且与脂肪生成相关。在隔夜禁食状态下，食物摄入量与脂肪生成呈负相关。我们得出结论，HIV 感染的特点是脂肪合成代谢异常。这适用于去脂体重减少的受试者和 T 细胞计数正常的无症状 HIV 阳性受试者。前一种观察可能对消耗综合征的病理生理学和治疗有影响。后一种观察结果与早期艾滋病毒疾病中免疫反应的激活和病毒非潜伏状态一致。
We measured de novo lipogenesis in human immunodeficiency virus (HIV) infected men using a newly developed stable isotope method. HIV-infected subjects with a history of weight loss (n = 17, mean weight loss 14.9 +/- 3.2 kg), asymptomatic HIV-seropositive subjects with normal CD4 T-cell counts (n = 7) and healthy HIV seronegative controls (n = 11) were studied. Hepatic lipogenesis was determined by infusion of [2-13C]-acetate, using the recently described xenobiotic probe technique with mass isotopomer analysis. Hepatic acetyl-coenzyme A enrichment was measured by high performance liquid chromatography/mass spectrometry of secreted sulfamethoxazole-acetate, with measurement of incorporation into very low density lipoprotein-fatty acids by gas chromatography-mass spectrometry. Circulating tumor necrosis factor (TNF), interleukin-1 (IL-1), interferon alpha (IFN alpha), insulin, and triglycerides were measured concurrently, and 7-day weighed food records were performed. De novo hepatic lipogenesis was increased 3- to 4-fold in HIV-infected subjects with weight loss compared to normal controls (P < 0.05 for palmitate and stearate in both overnight-fasted and fed states), and was also significantly increased in asymptomatic HIV seropositive subjects. Circulating TNF and IL-1 were not measurable in any subject (detection limit 2 pg/ml for IL-1 and 20 pg/ml for TNF). Serum IFN alpha was measurable in 11 out of 17 subjects with wasting and correlated significantly with de novo lipogenesis in overnight-fasted but not fed states. Serum IFN alpha was unmeasurable in asymptomatic HIV-infected subjects despite elevated lipogenic rates. Serum triglyceride concentrations were elevated in subjects with weight loss (2.09 +/- 0.28 mmol/L) and asymptomatic HIV-positives (1.34 +/- 0.34 mmol/L) in comparison to controls (0.67 +/- 0.08 mmol/L), and correlated with lipogenesis. Food intake correlated inversely with lipogenesis in the overnight-fasted state. We conclude that HIV infection is characterized by abnormal fat anabolism. This applies to subjects with reduced lean body mass and to asymptomatic HIV-positive subjects with normal T-cell counts. The former observation may have implications for the pathophysiology and treatment of the wasting syndrome. The latter observation is consistent with activation of the immune response and a state of viral nonlatency in early HIV disease.