Hesselbarth Nico, Pettinelli Chiara, Gericke Martin, Berger Claudia, Kunath Anne, Stumvoll Michael, Blüher Matthias, Klöting Nora
Department of Medicine, University of Leipzig, D-04103 Leipzig, Germany.
Institute of Anatomy, University of Leipzig, D-04103 Leipzig, Germany.
Biochem Biophys Res Commun. 2015 Aug 28;464(3):724-9. doi: 10.1016/j.bbrc.2015.07.015. Epub 2015 Jul 8.
Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to generate inducible conditional transgenic mouse models. Activation of ER signaling plays an important role in the regulation of adipose tissue (AT) metabolism. We therefore tested the hypothesis that tamoxifen administration causes changes in AT biology in vivo. 12 weeks old male C57BL/6NTac mice were treated with either tamoxifen (n = 18) or vehicle (n = 18) for 5 consecutive days. Tamoxifen treatment effects on body composition, energy homeostasis, parameters of AT biology, glucose and lipid metabolism were investigated up to an age of 18 weeks. We found that tamoxifen treatment causes: I) significantly increased HbA1c, triglyceride and free fatty acid serum concentrations (p < 0.01), II) browning of subcutaneous AT and increased UCP-1 expression, III) increased AT proliferation marker Ki67 mRNA expression, IV) changes in adipocyte size distribution, and V) transient body composition changes. Tamoxifen may induce changes in body composition, whole body glucose and lipid metabolism and has significant effects on AT biology, which need to be considered when using Tamoxifen as a tool to induce conditional transgenic mouse models. Our data further suggest that tamoxifen-treated wildtype mice should be characterized in parallel to experimental transgenic models to control for tamoxifen administration effects.
他莫昔芬是一种选择性雌激素受体（ER）调节剂，广泛用于构建可诱导的条件性转基因小鼠模型。ER信号的激活在脂肪组织（AT）代谢调节中起重要作用。因此，我们检验了以下假设：给予他莫昔芬会在体内引起AT生物学变化。对12周龄的雄性C57BL/6NTac小鼠连续5天给予他莫昔芬（n = 18）或赋形剂（n = 18）。研究了他莫昔芬治疗对身体组成、能量稳态、AT生物学参数、葡萄糖和脂质代谢的影响，直至18周龄。我们发现他莫昔芬治疗会导致：I）糖化血红蛋白、甘油三酯和游离脂肪酸血清浓度显著升高（p < 0.01），II）皮下AT褐变和UCP-1表达增加，III）AT增殖标志物Ki67 mRNA表达增加，IV）脂肪细胞大小分布改变，以及V）身体组成的短暂变化。他莫昔芬可能会引起身体组成、全身葡萄糖和脂质代谢的变化，并对AT生物学有显著影响，在将他莫昔芬用作诱导条件性转基因小鼠模型的工具时需要考虑这些影响。我们的数据进一步表明，应将经他莫昔芬处理的野生型小鼠与实验性转基因模型平行进行表征，以控制他莫昔芬给药的影响。
