Sutinen Jussi, Kannisto Katja, Korsheninnikova Elena, Fisher Rachel M, Ehrenborg Ewa, Nyman Tuulikki, Virkamäki Antti, Funahashi Tohru, Matsuzawa Yuji, Vidal Hubert, Hamsten Anders, Yki-Järvinen Hannele
Division of Diabetes, Department of Medicine, Helsinki University Central Hospital, PO Box 348, FIN-00029 HUS, Helsinki, Finland.
Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E941-9. doi: 10.1152/ajpendo.00490.2003. Epub 2004 Jan 28.
Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and PPARgamma coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARdelta, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.
高效抗逆转录病毒疗法（HAART）改善了人类免疫缺陷病毒（HIV）感染患者的预后，但会引发严重不良事件，如脂肪代谢障碍和胰岛素抵抗。在一项随机、双盲、安慰剂对照试验中，罗格列酮并未增加HAART相关脂肪代谢障碍（HAL）患者的皮下脂肪，不过它减轻了胰岛素抵抗并降低了肝脏脂肪含量。本研究的目的是检测罗格列酮对30例HAL患者皮下脂肪组织基因表达的影响。采用实时定量PCR测定皮下脂肪组织中的mRNA浓度。与安慰剂相比，罗格列酮（8毫克/天）治疗24周显著增加了脂联素、过氧化物酶体增殖物激活受体γ（PPARγ）和PPARγ共激活因子1的表达，并降低了IL-6的表达。参与脂肪生成、脂肪酸代谢或葡萄糖转运的其他基因，如酰基辅酶A合成酶、脂肪细胞脂质结合蛋白、CD45、脂肪酸转运蛋白-1和-4、葡萄糖转运蛋白1（GLUT1）、葡萄糖转运蛋白4（GLUT4）、角质形成细胞脂质结合蛋白、脂蛋白脂肪酶、PPARδ和固醇调节元件结合蛋白-1c的表达未发生变化。罗格列酮还显著提高了血清脂联素浓度。血清脂联素浓度的变化与空腹血清胰岛素浓度和肝脏脂肪含量的变化呈负相关。总之，罗格列酮诱导了HAL患者皮下脂肪组织基因表达的显著变化，并改善了胰岛素抵抗。脂联素表达的增加可能介导了罗格列酮在这些患者中大部分有益的胰岛素增敏作用。
