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

哺乳动物甲状腺激素（TH）的管理导致基础代谢率和产热的增加。我们以前的人体研究表明，BAT的活动，这是中心的产热，是由TH的影响。此外，使用高，低，和甲状腺功能正常的小鼠模型，我们发现的证据表明，TH诱导褐色脂肪细胞的发生在白色脂肪库。在白色脂肪组织驻留的巨噬细胞的分析给出了第一个证据TH的作用，在诱导的替代激活的巨噬细胞，这在目前的研究中讨论密切交织在一起的布朗宁的白色脂肪组织。因此，我们推测TH启动和调节WAT的布朗宁。本项目的主要目的是确定最终导致TH诱导的白色脂肪组织布朗宁的潜在机制。这将在以下三个子项目中进行测试，以解决特定的目标：（1）TH对WAT布朗宁的中枢和细胞效应的歧视;（II）使用PET/MRI表征甲状腺功能亢进WAT中棕色脂肪细胞的代谢活性;（III）TH对交替激活的巨噬细胞诱导的产热作用的定义。因此，TH刺激白色脂肪组织布朗宁可能是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.