Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
Endocrinology. 2011 Sep;152(9):3571-81. doi: 10.1210/en.2011-1066. Epub 2011 Jul 19.
Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism.
甲状腺激素加速能量消耗（EE），对于冷诱导产热至关重要。为了确定甲状腺激素在从饮食中消耗卡路里方面所起的代谢作用，将甲状腺功能减退的小鼠在综合实验动物监测系统中研究了 60 天。甲状腺功能减退症减少了热量摄入和体脂肪，同时下调了骨骼肌中的基因，但不影响棕色脂肪组织的产热程序，而不影响每日 EE。只有在热中性（30°C）时，甲状腺功能减退症小鼠的 EE 率才会变慢，这表明甲状腺功能减退症的代谢反应取决于环境温度。这种机制的一个副产品是，在室温（22°C）下，甲状腺功能减退症小鼠可以防止饮食引起的肥胖症，即只有在热中性时，将甲状腺功能减退症小鼠置于高脂肪饮食（HFD）上才会肥胖。这与甲状腺功能正常的对照组形成对比，对照组在任何温度下都因 HFD 而增加了更多的体重和脂肪，激活了棕色脂肪组织并加速了每日 EE，但不会加速骨骼肌的产热程序。在甲状腺功能正常的对照组的肝脏中，HFD 导致甘油三酯含量增加约 5 倍，关键代谢基因的表达增加，而适应 30°C 可使甘油三酯含量减半，并使基因表达正常化。然而，在甲状腺功能减退症小鼠中，HFD 诱导的肝脏变化在 30°C 下持续存在，导致明显的肝脂肪变性。适应热中性极大地改善了葡萄糖稳态，但这不受甲状腺功能减退症的影响。总之，甲状腺功能减退症小鼠对环境温度的代谢敏感，构成了一种定义对饮食诱导的肥胖症和肝脂质代谢的抗性的机制。
