Thyroid hormone (TH) has a profound effect on energy metabolism and systemic homeostasis. Adipose tissues are crucial for maintaining whole-body homeostasis, however, whether TH regulates systemic metabolic homeostasis through its action on the adipose tissues is unclear. Here, we demonstrate that systemic administration of triiodothyronine (T3), the active form of TH, affects both inguinal white adipose tissue (iWAT) and whole-body metabolism. Taking advantage of the mouse model lacking adipocyte TH receptor α (TRα) or β (TRβ) we show that TRβ is the major TR isoform that mediates the T3 action on the expression of genes involved in multiple metabolic pathways in iWAT, including glucose uptake and usage, de novo fatty acid synthesis, and both UCP1-dependent and -independent thermogenesis. Moreover, our results indicate that ChREBP in iWAT is regulated by T3, thereby being critically involved in T3-regulated glucose and lipid metabolism and energy dissipation. Meanwhile, mice with adipocyte TRβ deficiency are susceptible to diet-induced obesity and metabolic dysregulation, suggesting that TRβ in adipocytes may sever as a potential target for metabolic diseases.

中文翻译：

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脂肪细胞甲状腺激素β受体介导的激素作用微调细胞内糖脂代谢和全身稳态

甲状腺激素 (TH) 对能量代谢和全身稳态具有深远影响。脂肪组织对于维持全身稳态至关重要，但是，TH 是否通过其对脂肪组织的作用来调节全身代谢稳态尚不清楚。在这里，我们证明了三碘甲腺原氨酸 (T3)（TH 的活性形式）的全身给药会影响腹股沟白色脂肪组织 (iWAT) 和全身代谢。利用缺乏脂肪细胞 TH 受体 α (TRα) 或 β (TRβ) 的小鼠模型，我们发现 TRβ 是主要的 TR 亚型，它介导 T3 对参与 iWAT 多种代谢途径的基因表达的作用，包括葡萄糖摄取和使用、脂肪酸从头合成以及 UCP1 依赖性和非依赖性产热作用。而且，我们的结果表明 iWAT 中的 ChREBP 受 T3 调节，因此关键参与 T3 调节的葡萄糖和脂质代谢和能量耗散。同时，脂肪细胞 TRβ 缺乏的小鼠易患饮食诱导的肥胖和代谢失调，这表明脂肪细胞中的 TRβ 可能成为代谢疾病的潜在靶点。