Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Il-Won Dong, Gang-Nam Gu, Seoul 135-710, Korea.
J Clin Endocrinol Metab. 2010 Mar;95(3):1371-7. doi: 10.1210/jc.2009-1489. Epub 2010 Jan 8.
Prader-Willi syndrome (PWS), a genetic disorder characterized by obesity in early childhood, is reported to have elevated levels of adiponectin. The effects of adiponectin are mediated by adiponectin receptors (ADIPORs) that include ADIPOR1 and ADIPOR2. There is evidence that several cytokines, including adiponectin, TNF-alpha, and IL-6, are involved in insulin sensitivity.
We measured the relative expression of adiponectin, ADIPORs, several proinflammatory cytokines including TNF-alpha, and IL-6 expression in peripheral blood mononuclear cells (PBMCs) of children with PWS and obese comparators using real-time PCR. Their correlation with homeostasis model assessment insulin resistance index (HOMA-IR) was analyzed.
Thirty children with PWS (median age 7.1 yr, 18 males, 12 females) that were being treated with GH and 32 obese children not receiving GH treatment (median age 9.1 yr, 15 males, 17 females) for comparison were enrolled.
The PWS children had increased expression of ADIPOR2 (P = 0.02) and decreased expression of IL-6 (P = 0.03) compared with the comparison group. Moreover, there was a significant positive correlation between the ADIPORs and TNF-alpha (ADIPOR1 vs. TNF-alpha: r = 0.66, P < 0.001 in PWS, r = 0.80, P < 0.001 in comparison group; ADIPOR2 vs. TNF-alpha: r = 0.69, P < 0.001 in comparison group). The ADIPORs in the comparison group showed significant negative correlation with HOMA-IR (ADIPOR1 vs. HOMA-IR; rho = -0.41, P = 0.02, ADIPOR2 vs. HOMA-IR; rho = -0.46, P < 0.01).
The results of this study showed that inflammatory cytokine expression was closely associated with the expression of the ADIPORs in the PBMCs of both the children with PWS and the comparison group. Moreover, ADIPOR2 expression was highly expressed in the PBMCs of the children with PWS. A further study on the mechanism of increased expression of ADIPOR2 and its correlation with the expression of TNF-alpha in the PBMCs using the non-GH-treated PWS and obese control will be warranted because this study compared GH-treated PWS with an obese comparator group.
普拉德-威利综合征（PWS）是一种以儿童早期肥胖为特征的遗传性疾病，据报道其脂联素水平升高。脂联素的作用是通过脂联素受体（ADIPORs）介导的，其中包括 ADIPOR1 和 ADIPOR2。有证据表明，几种细胞因子，包括脂联素、TNF-α 和 IL-6，参与胰岛素敏感性。
我们使用实时 PCR 测量了 PWS 患儿和肥胖对照组外周血单个核细胞（PBMCs）中脂联素、ADIPORs、几种促炎细胞因子（包括 TNF-α 和 IL-6）的相对表达，并分析了它们与稳态模型评估胰岛素抵抗指数（HOMA-IR）的相关性。
本研究纳入了 30 名正在接受 GH 治疗的 PWS 患儿（中位年龄 7.1 岁，男性 18 名，女性 12 名）和 32 名未接受 GH 治疗的肥胖患儿（中位年龄 9.1 岁，男性 15 名，女性 17 名）作为对照组。
与对照组相比，PWS 患儿的 ADIPOR2 表达增加（P = 0.02），IL-6 表达减少（P = 0.03）。此外，ADIPORs 与 TNF-α 之间存在显著正相关（ADIPOR1 与 TNF-α：r = 0.66，P < 0.001 在 PWS 组，r = 0.80，P < 0.001 在对照组；ADIPOR2 与 TNF-α：r = 0.69，P < 0.001 在对照组）。对照组的 ADIPORs 与 HOMA-IR 呈显著负相关（ADIPOR1 与 HOMA-IR：rho = -0.41，P = 0.02；ADIPOR2 与 HOMA-IR：rho = -0.46，P < 0.01）。
本研究结果表明，炎症细胞因子的表达与 PWS 患儿和对照组 PBMCs 中 ADIPORs 的表达密切相关。此外，PWS 患儿 PBMCs 中 ADIPOR2 的表达水平较高。由于本研究将 GH 治疗的 PWS 与肥胖对照组进行了比较，因此需要进一步研究非 GH 治疗的 PWS 及其与 PBMCs 中 TNF-α 表达增加的机制。
