Definition of central and cellular effects of thyroid hormones on white adipose tissue browning

哺乳动物服用甲状腺激素（TH）会导致基础代谢率和产热率的增加。我们之前的人体研究表明，BAT是生热的中心部位，其活性受到TH的影响。此外，通过使用甲状腺亢进、甲状腺低下和甲状腺正常小鼠模型，我们发现了TH诱导白色脂肪库中棕色脂肪细胞发生的证据。对白色脂肪组织中巨噬细胞的分析首次证明了TH在诱导选择性活化巨噬细胞中的作用，目前的研究认为巨噬细胞与白色脂肪组织的褐变密切相关。因此，我们假设TH启动并调节WAT的褐变。这个项目的主要目的是确定潜在的机制，最终有助于TH诱导白色脂肪组织褐变。这将在以下三个子项目中进行测试，以解决具体目标：(1)TH对WAT褐变的中枢和细胞效应的区分；（II）利用PET/MRI表征甲状腺机能亢进WAT中棕色脂肪细胞的代谢活性；（III） TH对选择性活化巨噬细胞诱导产热作用的定义。从长远来看，通过TH的作用刺激白色脂肪组织褐变可能转化为提高能量消耗的有效疗法。

Administration of thyroid hormones (TH) to mammals leads to an increase in basal metabolic rate and thermogenesis. Our previous human study demonstrates that the activity of BAT, which is the central place for thermogenesis, is influenced by TH. Furthermore, using a mouse model of hyper-, hypo-, and euthyroid mice, we found evidence that TH induce the occurrence of brown adipocytes in white adipose depots. The analysis of in white adipose tissue residing macrophages gave first evidence for a role of TH in the induction of alternatively activated macrophages, which in current studies are discussed to be closely intertwined with browning of white adipose tissues. Thus, we hypothesize that TH initiate and regulate browning of WAT. The main aim of this project is to identify the underlying mechanisms which finally contribute to the TH induced browning of white adipose tissue. This will be tested in three following subprojects addressing specific aims: (1) The discrimination of central and cellular effects of TH on WAT browning; (II) The characterization of the metabolic activity of the brown adipocytes in hyperthyroid WAT using PET/MRI, (III) Definition of the role of TH on alternatively activated macrophage induced thermogenesis. Perspectively, the stimulation of white adipose tissue browning via the action of TH might be translated into an effective therapy to raise energy expenditure.