Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6
Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6
复制标题
DOI：
10.1152/ajpendo.00307.2010
复制
发表时间：
2011-02-01
影响因子：
5.1
通讯作者：
Abumrad, Naji N.
中科院分区：
文献类型：
--
作者：
Hajri, Tahar;Tao, Huan;Abumrad, Naji N.
Hajri T, Tao H, Wattacheril J, Marks-Shulman P, Abumrad NN。胰岛素对脂联素产生的调节：与肿瘤坏死因子- α和白细胞介素-6的相互作用。[J] .中国生物医学工程学报，2011,31(2):559 - 563。首次发表于2010年11月9日；doi: 10.1152 / ajpendo.00307.2010。肥胖通常与胰岛素抵抗、低度全身性炎症和血浆脂联素降低有关。脂肪组织的炎症也会增加，但尚不清楚脂联素水平的降低是否与胰岛素活性失调和/或促炎介质的增加有关。在这项研究中，我们通过体内和体外方法研究了胰岛素、肿瘤坏死因子- α (tnf - α)和白细胞介素6 （IL-6）在调节脂联素产生中的相互作用。血浆脂联素和胰岛素抵抗和炎症参数在瘦和肥胖胰岛素抵抗的队列中进行了评估。此外，使用高胰岛素-正糖钳在体内和脂肪组织（AT）培养中检测了胰岛素的作用。与瘦人相比，肥胖胰岛素抵抗者的总脂联素水平，尤其是高分子量异构体的水平异常低。高胰岛素钳夹数据证实了肥胖患者的胰岛素抵抗状态，并显示胰岛素输注显著增加了瘦而非肥胖患者的血浆脂联素（P < 0.01）。同样，胰岛素增加了瘦人和非肥胖者AT外植体的总脂联素释放。肥胖受试者AT中tnf - α和IL-6的表达和分泌显著升高，与脂联素的表达和分泌呈负相关。在3T3-L1和人脂肪细胞培养中，胰岛素强烈增强脂联素的表达（2倍）和分泌（3倍）。tnf - α，而不是IL-6，强烈反对胰岛素的刺激作用。有趣的是，tnf - α的抑制作用尤其针对脂联素的HMW异构体。总之，这些研究表明胰岛素上调脂联素的表达和释放，而tnf - α对抗胰岛素的刺激作用。胰岛素抵抗和增加的tnf - α产生的结合可以解释肥胖胰岛素抵抗受试者血浆中脂联素水平的下降和同分异构体组成的改变。
Hajri T, Tao H, Wattacheril J, Marks-Shulman P, Abumrad NN. Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-alpha and interleukin-6. Am J Physiol Endocrinol Metab 300: E350-E360, 2011. First published November 9, 2010; doi: 10.1152/ajpendo.00307.2010.-Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects (P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-alpha and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-alpha, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-alpha was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-alpha opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-alpha production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.