Table_1_Free Thyroxine Levels are Associated with Cold Induced Thermogenesis in Healthy Euthyroid Individuals.docx

Thyroid hormone (TH) is an important regulator of mammalian metabolism and facilitates cold induced thermogenesis (CIT) in brown adipose tissue (BAT). Profound hypothyroidism or hyperthyroidism lead to alterations in BAT function and CIT. In euthyroid humans the inter-individual variation of thyroid hormones is relatively large. Therefore, we investigated whether levels of free thyroxine (T4) or free triiodothyronine (T3) are positively associated with CIT in euthyroid individuals. We performed an observational study in 79 healthy, euthyroid volunteers (mean age 25.6 years, mean BMI 23.0 kg · m-2). Resting energy expenditure (REE) was measured by indirect calorimetry during warm conditions (EEwarm) and after a mild cold stimulus of two hours (EEcold). CIT was calculated as the difference between EEcold and EEwarm. BAT activity was assessed by 18F-FDG-PET after a mild cold stimulus in a subset of 26 participants. EEcold and CIT were significantly related to levels of free T4 (R2 = 0.11, p=0.0025 and R2 = 0.13, p=0.0011, respectively) but not to free T3 and TSH. Cold induced BAT activity was also associated with levels of free T4 (R2 = 0.21, p=0.018). CIT was approximately fourfold higher in participants in the highest tertile of free T4 as compared to the lowest tertile. Additionally, free T4 was weakly, albeit significantly associated with outdoor temperature seven days prior to the respective study visit (R2 = 0.06, p=0.037). These finding suggests that variations in thyroid hormone levels within the euthyroid range are related to the capability to adapt to cool temperatures and affect energy balance.

甲状腺激素（Thyroid hormone, TH）是哺乳动物代谢的关键调控因子，可促进棕色脂肪组织（brown adipose tissue, BAT）发生冷诱导产热（cold induced thermogenesis, CIT）。重度甲状腺功能减退或亢进均会改变BAT功能与CIT水平。在甲状腺功能正常的人群中，甲状腺激素的个体间差异相对较大。因此，本研究旨在探讨甲状腺功能正常人群中，游离甲状腺素（free thyroxine, T4）与游离三碘甲状腺原氨酸（free triiodothyronine, T3）水平是否与CIT呈正相关。本研究开展了一项观察性研究，纳入79名健康甲状腺功能正常的志愿者作为研究对象，其平均年龄为25.6岁，平均体质量指数（Body Mass Index, BMI）为23.0 kg·m⁻²。采用间接测热法分别测定受试者在常温环境下的静息能量消耗（resting energy expenditure, REE，记为EEwarm）以及2小时轻度冷刺激后的静息能量消耗（记为EEcold）；CIT通过EEcold与EEwarm的差值计算得到。本研究对其中26名受试者在轻度冷刺激后，采用18F-脱氧葡萄糖正电子发射断层显像（18F-fluorodeoxyglucose positron emission tomography, 18F-FDG-PET）评估BAT活性。EEcold与CIT水平均与游离T4水平呈显著相关（决定系数R²分别为0.11、0.13，对应P值分别为0.0025、0.0011），但与游离T3及促甲状腺激素（thyroid-stimulating hormone, TSH）水平无显著关联。冷刺激诱导的BAT活性同样与游离T4水平显著相关（R²=0.21，P=0.018）。游离T4水平最高三分位组受试者的CIT水平约为最低三分位组的4倍。此外，尽管相关性较弱，但游离T4水平与受试者对应研究访视前7天的室外温度呈显著相关（R²=0.06，P=0.037）。上述研究结果表明，甲状腺功能正常范围内的甲状腺激素水平变化，与人体适应低温环境的能力及能量平衡状态密切相关。