Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Diabetes Obes Metab. 2010 Dec;12(12):1084-9. doi: 10.1111/j.1463-1326.2010.01297.x.
To test the hypothesis that ascorbic acid (AA) and thiazolidinedione (TZD) would have additive effects on HMW adiponectin secretion by virtue of different modes of action.
We determined the effects of supplementation of AA and/or TZD on expression and secretion of total and HMW adiponectin from human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes in the absence or presence of the proinflammatory cytokine TNFα.
AA supplementation significantly increased secretion of HMW adiponectin (1.7-fold) without altering adiponectin expression or total adiponectin secretion. TZD significantly increased expression (3-fold) and secretion of total (1.4-fold) but not HMW adiponectin. Combined supplementation resulted in a significant increase in expression (3-fold) and secretion of total (1.8-fold) and HMW (5-fold) adiponectin. Similar results were seen in cells co-treated with TNFα.
These data show that AA and TZD have synergistic rather than simple additive effects on secretion of HMW adiponectin from human adipocytes and raise the possibility that differences in AA levels may contribute to the variability in adiponectin multimer profiles and efficacy of TZD in humans. Our results also provide a rationale for longitudinal clinical trials investigating the effects of AA supplementation with or without TZD on adiponectin and metabolic profiles.
通过不同的作用方式,检验抗坏血酸(AA)和噻唑烷二酮(TZD)具有协同增加高分子量(HMW)脂联素分泌作用的假说。
我们测定了补充 AA 和/或 TZD 对人 Simpson-Golabi-Behmel 综合征(SGBS)脂肪细胞中总脂联素和 HMW 脂联素表达和分泌的影响,同时存在或不存在促炎细胞因子 TNFα。
AA 补充显著增加了 HMW 脂联素的分泌(增加了 1.7 倍),而不改变脂联素的表达或总脂联素的分泌。TZD 显著增加了总脂联素(增加了 3 倍)和分泌(增加了 1.4 倍),但不增加 HMW 脂联素。联合补充导致总脂联素(增加了 1.8 倍)和 HMW(增加了 5 倍)脂联素的表达和分泌显著增加。在与 TNFα 共同处理的细胞中也观察到了类似的结果。
这些数据表明,AA 和 TZD 对人脂肪细胞中 HMW 脂联素的分泌具有协同而非简单的相加作用,并提出 AA 水平的差异可能导致脂联素多聚体谱的变异性和 TZD 在人类中的疗效差异的可能性。我们的结果还为进行纵向临床试验提供了依据,研究 AA 补充与或不与 TZD 联合对脂联素和代谢谱的影响。