Villarroya Joan, Diaz-Delfin Julieta, Hyink Deborah, Domingo Pere, Giralt Marta, Klotman Paul E, Villarroya Francesc
Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
Antivir Ther. 2010;15(7):1021-8. doi: 10.3851/IMP1669.
Lipodystrophy in HIV type-1 (HIV-1)-infected patients is the consequence of effects originating from antiretroviral treatment and HIV-1 infection. We have studied adipose tissues and circulating parameters in mice bearing the HIV-1 transgene as a model to provide insight into the role of HIV-1-infection-related events in fat alterations.
Heterozygous transgenic mice expressing a 7.7 kb HIV-1 construct (Tg26+/-) were used. Cytokine and adipokine levels were quantified using multiplex procedures. Gene expression and mitochondrial DNA abundance in visceral and subcutaneous white adipose tissues and in brown fat were determined using quantitative real-time PCR.
The amount of visceral, but not subcutaneous, adipose depot was lower in Tg26+/- mice. Serum proinflammatory cytokine levels were increased in Tg26+/- mice, whereas adiponectin and leptin levels were reduced. Gene expression of monocyte chemoattractant protein-1 was induced in visceral and subcutaneous fat, whereas tumour necrosis factor-α and interleukin-6 were induced in visceral and subcutaneous white adipose tissues, respectively. Adiponectin and leptin gene expression was repressed in all white fat depots, in concert with reduced expression of peroxisome proliferator-activated receptor γ, a master controller of adipogenesis. In brown fat, a coordinate induction in the expression of thermogenesis marker genes was observed.
HIV-1 transgene expression in mice causes changes in adipose tissue reminiscent of those in patients with HIV-1 lipodystrophy, particularly early pretreatment changes. These data support a role for HIV-1-infection-related events in eliciting adipose tissue dysfunction. The Tg26+/- mouse appears as a promising model to assess the effects of HIV-1 infection on adipose tissue and for determining the effects of antiretroviral drugs on an HIV-1-infected background.
1型人类免疫缺陷病毒（HIV-1）感染患者的脂肪代谢障碍是抗逆转录病毒治疗和HIV-1感染所产生影响的结果。我们研究了携带HIV-1转基因的小鼠的脂肪组织和循环参数，以此作为模型来深入了解HIV-1感染相关事件在脂肪改变中的作用。
使用表达7.7 kb HIV-1构建体的杂合转基因小鼠（Tg26+/-）。采用多重检测方法对细胞因子和脂肪因子水平进行定量。使用定量实时聚合酶链反应测定内脏和皮下白色脂肪组织以及棕色脂肪中的基因表达和线粒体DNA丰度。
Tg26+/-小鼠的内脏脂肪量减少，但皮下脂肪量未减少。Tg26+/-小鼠的血清促炎细胞因子水平升高，而脂联素和瘦素水平降低。单核细胞趋化蛋白-1的基因表达在内脏和皮下脂肪中被诱导，而肿瘤坏死因子-α和白细胞介素-6分别在内脏和皮下白色脂肪组织中被诱导。所有白色脂肪库中的脂联素和瘦素基因表达均受到抑制，同时过氧化物酶体增殖物激活受体γ（脂肪生成的主要调控因子）的表达也降低。在棕色脂肪中，观察到产热标记基因表达的协同诱导。
小鼠中的HIV-1转基因表达导致脂肪组织发生变化，这与HIV-1脂肪代谢障碍患者的变化相似，尤其是治疗前早期的变化。这些数据支持HIV-1感染相关事件在引发脂肪组织功能障碍中起作用。Tg26+/-小鼠似乎是评估HIV-1感染对脂肪组织的影响以及确定抗逆转录病毒药物在HIV-1感染背景下的作用的一个有前景的模型。
