*Department of Biochemistry and Molecular Biology; and †Institut de Biomedicina (IBUB), University of Barcelona, Barcelona, Spain; ‡CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Barcelona, Spain; §Red de Investigación en SIDA (RIS), Barcelona, Spain; and Departments of ‖Infectious Diseases; ¶General Surgery; and #Dermatology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
J Acquir Immune Defic Syndr. 2013 Oct 1;64(2):142-8. doi: 10.1097/QAI.0b013e31829bdb67.
Lipodystrophy in HIV-1-infected antiretroviral-treated patients is often associated with opposite alterations in adipose tissue depots as follows: lipoatrophy of subcutaneous adipose tissue (SAT) versus lipohypertrophy of visceral adipose tissue (VAT). We determined the specific molecular alterations in VAT relative to SAT in patients.
We analyzed the expression of marker genes of mitochondrial function, adipogenesis, and inflammation in a unique collection of 8 biopsies of omental VAT from HIV-1-infected antiretroviral-treated patients with lipodystrophy. For comparison, we analyzed SAT from 10 patients, and SAT and VAT from 10 noninfected individuals.
Quantitative real-time polymerase chain reaction of mitochondrial DNA and gene transcripts; immunoblot and multiplex for quantification of specific proteins.
Similar mitochondrial DNA depletion and abnormal increases in mitochondrial protein levels were found in VAT and SAT from patients. Transcript levels of adipogenesis and metabolism marker genes were unaltered in VAT but were decreased in SAT. Tumor necrosis factor α and CD68 were similarly induced in both adipose depots from patients, but other markers of inflammation-related pathways showed distinct alterations as follows: interleukin 18 and interleukin 1 receptor antagonist were induced only in SAT, whereas interleukin 6, interleukin 8, and monocyte chemoattractant protein 1 expression was reduced in VAT but not in SAT.
Mitochondrial alterations are similar in VAT and SAT from patients, whereas adipogenic gene expression is decreased in SAT but unaltered in VAT, highlighting the relevance of adipogenic processes in the differential alterations of fat depots. Specific disturbances in inflammatory status in VAT relative to SAT are present. Milder induction of proinflammatory signaling in VAT could be involved in preventing fat wasting in this depot.
HIV-1 感染的抗逆转录病毒治疗患者的脂肪营养不良通常与以下相反的脂肪组织储存改变相关：皮下脂肪组织（SAT）的脂肪减少与内脏脂肪组织（VAT）的脂肪增生。我们确定了患者 VAT 相对于 SAT 的特定分子改变。
我们分析了 8 例脂肪营养不良的 HIV-1 感染抗逆转录病毒治疗患者的网膜 VAT 活检的线粒体功能、脂肪生成和炎症标记基因的表达。为了比较，我们分析了 10 例患者的 SAT，以及 10 例未感染个体的 SAT 和 VAT。
定量实时聚合酶链反应线粒体 DNA 和基因转录物；免疫印迹和多重定量特定蛋白质。
在患者的 VAT 和 SAT 中发现了相似的线粒体 DNA 耗竭和异常增加的线粒体蛋白水平。脂肪生成和代谢标记基因的转录水平在 VAT 中未改变，但在 SAT 中降低。肿瘤坏死因子-α和 CD68 在患者的两个脂肪储存库中均被相似地诱导，但炎症相关途径的其他标记物显示出以下不同的改变：白细胞介素 18 和白细胞介素 1 受体拮抗剂仅在 SAT 中被诱导，而白细胞介素 6、白细胞介素 8 和单核细胞趋化蛋白 1 的表达在 VAT 中降低，但在 SAT 中不降低。
患者的 VAT 和 SAT 中存在相似的线粒体改变，而 SAT 中的脂肪生成基因表达降低而 VAT 中未改变，这突出了脂肪生成过程在脂肪储存库的差异改变中的相关性。在 VAT 中存在与 SAT 相比特定的炎症状态的改变。在 VAT 中更温和的促炎信号诱导可能参与防止该储存库的脂肪丢失。
