Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, and School of Molecular Biosciences, Washington State University, Pullman, WA, 99164, USA.
School of Food Sciences, Washington State University, Pullman, WA, 99164, USA.
Int J Obes (Lond). 2020 Jan;44(1):226-234. doi: 10.1038/s41366-019-0330-3. Epub 2019 Jan 31.
Tamoxifen-inducible Cre/lox site-specific recombination technology has been widely used to generate conditional transgenic mice. As an estrogen receptor ligand, tamoxifen itself potentially affects energy metabolism, which may confound interpretation of data especially in metabolic studies. Considering sexual dimorphism, in this study, the effects of low-dose tamoxifen administration on energy metabolism, and browning of adipose tissues in female and male mice were investigated.
Female and male C57/BL6 mice were injected with tamoxifen oil solution (i.p.) and then housed at both room temperature (23 ± 2 °C) and cold environment (6 ± 1 °C). Serum, brown and white adipose tissues were obtained, and the effects of tamoxifen administration on energy metabolism and the browning of adipose tissues were evaluated.
At 25 mg/kg body weight (BDW), tamoxifen administration for 3 alternative days decreased the percentage of inguinal and gonadal white adipose tissue weights in female mice accompanied by the up-regulation of thermogenesis in adipose tissues. In contrast, this dosage of tamoxifen did not induce noticeable changes in the energy metabolism and thermogenesis of adipose tissue in male mice under room temperature. Consistently, under cold stimulus, substantial browning of adipose tissues was observed in female mice injected with tamoxifen (50 mg/kg BDW, single injection) but not in male mice. Two-way ANOVA tests also demonstrated significant interactions between tamoxifen treatment and gender on the expression of thermogenic markers in adipose tissues.
Tamoxifen, even at a low dose, remarkably increases thermogenesis in adipose tissues of female mice; meanwhile, such a low dose could be used in male mice for inducing gene recombination without confounding the interpretation of data related to metabolism and thermogenesis of adipose tissues.
他莫昔芬诱导型 Cre/lox 位点特异性重组技术已被广泛用于产生条件性转基因小鼠。作为雌激素受体配体，他莫昔芬本身可能会影响能量代谢，这可能会混淆数据的解释，特别是在代谢研究中。考虑到性别二态性，在这项研究中，我们研究了低剂量他莫昔芬给药对雌性和雄性小鼠能量代谢和脂肪组织棕色化的影响。
雌性和雄性 C57/BL6 小鼠经他莫昔芬油溶液（腹腔注射）处理后，分别在室温（23±2°C）和寒冷环境（6±1°C）下饲养。获取血清、棕色和白色脂肪组织，并评估他莫昔芬给药对能量代谢和脂肪组织棕色化的影响。
在 25mg/kg 体重（BDW）剂量下，他莫昔芬连续 3 天给药可降低雌性小鼠腹股沟和性腺白色脂肪组织的重量百分比，同时促进脂肪组织产热。相比之下，在室温下，该剂量的他莫昔芬对雄性小鼠的能量代谢和脂肪组织产热没有引起明显变化。同样，在寒冷刺激下，给予 50mg/kg BDW 剂量（单次注射）他莫昔芬的雌性小鼠的脂肪组织发生明显的棕色化，但雄性小鼠没有。双向方差分析也表明，他莫昔芬处理和性别对脂肪组织产热标志物表达的影响存在显著的交互作用。
即使低剂量的他莫昔芬也能显著增加雌性小鼠脂肪组织的产热；同时，这种低剂量可用于雄性小鼠诱导基因重组，而不会混淆与脂肪组织代谢和产热相关的数据解释。
