三磷酸腺苷敏感性鉀離子通道（KATP通道）是一種存在於人體不同部位的功能性通道，包括胰臟β細胞、大腦和棕色脂肪組織，它是由四個SURx亞基和四個Kir6.x亞基組成的八聚體複合物，而我們已經知道該通道在棕色脂肪組織中的功能作用。一些研究表明KATP通道在白色脂肪組織的脂質代謝中的存在和重要作用。所以我們使用了西方墨點法、即時聚合酶連鎖反應、免疫組織化學染色法來確認副睪白色脂肪中KATP通道的存在。脂毒性指的是游離脂肪酸的超載，這意味著非脂肪的器官或組織中有不正常的脂質累積，而這將導致脂肪胰島軸中KATP通道的運輸缺陷。脂肪島軸表示白色脂肪和胰島β細胞之間的雙向反饋迴路，在這個迴路中，胰島素刺激白色脂肪增加瘦素的產生和分泌，另一方面，瘦素進一步抑制胰島素釋放。而脂毒性也被認為在肥胖和糖尿病中起作用，這種情況可以通過長期注射給予棕櫚酸引起。棕櫚酸是人類日常飲食和血清中最常見的飽和游離脂肪酸，此外，我們發現給予小鼠棕櫚酸會下調KATP通道的表達並引起副睪白色脂肪中的NLRP3發炎反應。我們還使用了高脂肪飲食來建立肥胖模型，發現高脂肪飲食也會降低KATP通道的表達。KATP通道阻滯劑格列苯脲是第二型糖尿病的二線藥物，可以恢復脂毒性模型和肥胖模型中副睪白色脂肪中KATP通道的表達，減緩NLRP3發炎反應，包括降低NLRP3發炎小體的表達。此外，為了更深入研究副睪白色脂肪，我們使用iDISCO這個技術來看位於副睪白色脂肪中的交感神經支配，而我們觀察到高脂肪飲食和棕櫚酸注射損害了白色脂肪中的交感神經支配，格列苯脲則可以恢復交感神經支配。

ATP-sensitive potassium channel (KATP channel) is a functional channel found in different parts of the human body, including pancreatic β cells, brain, and brown adipose tissue. It is an octameric complex composed of four SURx subunits and four Kir6.x subunits. We have already known the functional role of this channel in brown adipose tissue. And a few researches have suggested the presence and the important role of KATP channel in lipid metabolism in white adipose tissue (WAT). So we use the Western blot, real-time polymerase chain reaction (qPCR), and immunohistochemistry (IHC) to check and confirm the presence of KATP channel in epididymal white adipose tissue (eWAT). Lipotoxicity, the overload of free fatty acid, which means abnormal lipid accumulation in non-adipose tissue, will cause defective trafficking of KATP channels in the adipo-insular axis. Adipo-insular axis indicates the bidirectional feedback loop between WAT and pancreatic β cells. In this loop, insulin increases leptin production and secretion by WAT. And leptin further suppresses insulin release. Lipotoxicity is also believed to have a role in obesity and diabetes. And this condition can be induced by chronic palmitic acid (PA) administration. PA is the most common saturated free fatty acid in the human daily diet and serum. Besides, we find PA treatment will downregulate the expression of KATP channel and trigger the NLRP3 inflammatory response in WAT, as we observed from the Western blot and immunohistochemistry results. We also use HFD to establish the obese model and find that HFD also decreases KATP channel expression. KATP channel blocker glibenclamide (GB) which is also the second-line drug for type 2 diabetes, can recover the KATP channel expression in lipotoxicity and obese models and alleviate the NLRP3 inflammation response, including reducing the expression of NLRP3 inflammasome. Moreover, iDISCO (immunolabeling-enabled three-dimensional imaging of solvent-cleared organs) for the sympathetic innervation in eWAT is employed to provide in-depth mechanistic investigation. We observed that HFD and PA injection impaired sympathetic innervation. And GB recovers the sympathetic innervation.

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