解偶联蛋白UCP1在将化学能转换为热能的产热过程中起关键作用，对维持恒温动物的体温至关重要。而肾上腺能信号则对应激条件下的适应性产热有重要调控作用。目前的研究揭示了许多重要的对Ucp1转录调控的机制。但是，棕色脂肪组织作为主要的产热器官，其中的UCP1蛋白水平并不会在刺激下剧烈波动。这表明在调控UCP1的表达水平之外，还有其他机制是棕色脂肪产热调控的关键。我们的初步数据显示，我们首先鉴定并命名的蛋白AIDA被肾上腺能信号通路的关键激酶PKA磷酸化，且在肾上腺能信号刺激下与UCP1结合；缺失AIDA的小鼠在肾上腺能信号刺激下耗氧量不上升，在低温刺激下无法维持体温。重要的是，AIDA并不影响UCP1的表达水平。本项目拟利用AIDA敲除小鼠，在分子、细胞器、细胞、组织以及小鼠个体水平研究AIDA在机体适应性产热中的作用及其调控机制，为进一步地理解和治疗肥胖及相关代谢疾病做出贡献。

The uncoupling protein 1 (UCP1) plays a critical function in thermogenesis by dissipating chemical energy, able to maintain the body temperature in homothermal organisms. Adrenergic signaling is vital to the regulation of adaptive thermogenesis in response to acute stresses. Most of the current researches have been focusing on the transcriptional regulation of Ucp1; however, in the major thermogenic organ, brown adipose tissue, protein levels of UCP1 are not dramatically changed upon stresses, indicating that mechanisms other than controlling the expression levels of Ucp1 play important roles. Our preliminary work has shown that the AIDA protein, which was initially cloned by our lab as a novel AXIN-interacting protein, is directly phosphorylated by protein kinase A (PKA) and forms complex with UCP1 in an adrenergic signaling-dependent manner. Deficiency of AIDA abrogates the adrenergic signaling-stimulated increase in oxygen consumption, and makes the mice more sensitive to cold stress. Importantly, AIDA has no effect on the expression of Ucp1. We will take advantage of Aida global knockout and tissue specific knockout mice to investigate the function of AIDA in UCP1-mediated adaptive thermogenesis and the underlying molecular mechanisms. It is anticipated that our research will uncover a direct link between adrenergic-activated PKA and UCP1 in body temperature control, highlighting the ancestral role of adrenalins in body physiology.