Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy
Adipose tissue lipin expression levels distinguish HIV patients with and without lipodystrophy
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DOI：
10.1038/sj.ijo.0803434
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Reue, K.
中科院分区：
文献类型：
--
作者：
Lindegaard, B.;Larsen, L. F.;Reue, K.
目的：脂肪代谢障碍是HIV感染者抗逆转录病毒治疗的主要并发症。其病理生理机制尚不清楚，但与抗逆转录病毒药物的抗脂肪形成作用有关。脂蛋白是一种新发现的对脂肪细胞分化至关重要的蛋白质，脂蛋白缺乏会导致小鼠脂肪营养不良。本研究的目的是确定是否改变lipin基因的表达与HIV lipodystrophy在human.Design：我们测量lipin mRNA水平在皮下腹部和股臀脂肪组织活检从HIV感染的患者或没有lipodystrophy，并在健康对照组。实时逆转录-PCR进行定量总脂蛋白的表达水平，和表达的两个脂蛋白亚型（脂蛋白-α和-β）所产生的替代mRNA splicing.Results：从小鼠的研究预测，脂蛋白的mRNA水平与四肢脂肪量在HIV患者，与较低的脂蛋白水平的脂肪代谢障碍患者比那些没有脂肪代谢障碍。然而，出乎意料的是，与脂肪代谢障碍患者和对照受试者相比，没有脂肪代谢障碍的HIV患者中脂蛋白-β表达的增加解释了这一点。此外，脂蛋白的表达水平呈负相关的脂肪组织表达的炎性细胞因子白细胞介素（IL）-6，IL-8和IL-18，这通常会增加在HIV相关lipoatrophytic.Conclusions：脂蛋白的表达水平升高与维护更大的脂肪量和更低的细胞因子表达在HIV感染的患者。基于脂蛋白在促进脂肪生成基因表达中的作用，这些观察结果提出了脂蛋白水平的变化可能导致脂肪组织质量和功能的变化的可能性，这些脂肪组织质量和功能可以区分有和没有脂肪代谢障碍的HIV患者。
Objective: Lipodystrophy is the major complication of antiretroviral therapy in HIV-infected patients. Its pathophysiology is not well understood, but has been linked to antiadipogenic effects of antiretroviral drugs. Lipin represents a newly characterized protein that is critical for adipocyte differentiation, and lipin deficiency leads to lipodystrophy in the mouse. The objective of this study was to determine whether altered lipin gene expression is associated with HIV lipodystrophy in humans.Design: We measured lipin mRNA levels in subcutaneous abdominal and femoral-gluteal adipose tissue biopsies from HIV-infected patients with or without lipodystrophy, and in healthy controls. Real-time reverse transcription-PCR was performed to quantitate total lipin expression levels, and expression of two lipin isoforms (lipin-alpha and -beta) that are generated by alternative mRNA splicing.Results: As predicted from studies with mice, lipin mRNA levels were correlated with limb fat mass in HIV patients, with lower lipin levels in patients with lipodystrophy than those without lipodystrophy. Unexpectedly, however, this was explained by an increase in lipin-beta expression in HIV patients without lipodystrophy compared to patients with lipodystrophy and control subjects. In addition, lipin expression levels were inversely correlated with adipose tissue expression of inflammatory cytokines interleukin (IL)-6, IL-8 and IL-18, which typically increase in HIV-associated lipoatrophy.Conclusions: Elevated lipin expression levels are associated both with the maintenance of greater fat mass and lower cytokine expression in HIV-infected patients. Based on the demonstrated role for lipin in promoting lipogenic gene expression, these observations raise the possibility that variations in lipin levels may contribute to variations in adipose tissue mass and function that distinguish HIV patients with and without lipodystrophy.