Lee Jennifer H, Bullen John W, Stoyneva Violeta L, Mantzoros Christos S
Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Stoneman 816, Boston, MA 02215, USA.
Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E625-32. doi: 10.1152/ajpendo.00184.2004. Epub 2004 Nov 2.
Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-alpha-/- mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an alpha-melanocyte-stimulating hormone analog, or CNTF(Ax15), a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-alpha-/- and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-alpha-/-, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTF(Ax15) treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTF(Ax15) treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.
抵抗素是一种由脂肪细胞分泌的激素，被认为是连接肥胖与胰岛素抵抗及糖尿病的纽带，但此前尚无研究对小鼠白色脂肪组织（WAT）中抵抗素mRNA表达及血清水平与胰岛素血症和血糖水平进行联合定量评估。因此，我们比较评估了瘦的C57BL/6J小鼠以及各种肥胖小鼠模型（包括饮食诱导肥胖的（DIO）C57BL/6J小鼠、高脂喂养的TNF-α-/-小鼠和棕色脂肪组织（BAT）缺陷的解偶联蛋白-白喉毒素A链（UCP1-DTA）小鼠）的WAT抵抗素mRNA表达和血清抵抗素水平。我们还研究了用减肥和胰岛素增敏化合物、α-黑素细胞刺激激素类似物MTII或睫状神经营养因子类似物CNTF（Ax15）治疗是否会改变瘦的和DIO C57BL/6J小鼠的抵抗素mRNA表达和/或循环水平。我们发现，DIO小鼠和瘦的C57BL/6J小鼠以及TNF-α-/-小鼠和野生型（WT）小鼠的抵抗素mRNA表达相似。然而，与瘦的对照相比，DIO C57BL/6J小鼠、高脂喂养的TNF-α-/-小鼠和UCP1-DTA小鼠的循环抵抗素水平更高。此外，虽然MTII处理24小时可上调抵抗素mRNA表达，而CNTF（Ax15）处理3天或7天可下调抵抗素mRNA表达，但MTII或CNTF（Ax15）处理不会改变循环抵抗素水平。另外，血清抵抗素水平而非抵抗素mRNA表达水平与体重相关，抵抗素mRNA表达和血清抵抗素水平均与血清胰岛素或葡萄糖水平无关。我们得出结论，WAT中抵抗素的转录调控与循环抵抗素水平不相关，并且循环抵抗素在小鼠胰岛素抵抗或血糖方面不太可能发挥主要的内分泌作用。
