The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global Adam17 knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using in vivo models. In this study, we developed an adipocyte-specific Adam17 knockout model using Adipoq-Cre-expressing mice crossed with Adam17-floxed mice. Using this model, we show that loss of adipocyte ADAM17 plays no evident role in baseline metabolic responses. Surprisingly, in a state of metabolic stress using high-fat diet (HFD), we observed that adipocyte ADAM17 had little effect overall on the metabolic phenotype as well as inflammatory cell populations. Using whole-body metabolic phenotyping, we show that loss of ADAM17 has no effect on energy utilization both at a baseline state as well as following HFD. However, lastly, using high-parameter flow cytometry, we show that loss of adipocyte ADAM17 alters macrophage and eosinophil populations following HFD. Overall, the studies presented here give more insight into the role of ADAM17 in metabolic responses and metabolic inflammation, specifically in adipocytes.

在炎症（包括代谢性炎症）的背景下，已经对ADAM17，其底物及其天然抑制剂的作用进行了充分的研究，结果不一。以前的研究使用全局表达的内源性ADAM17抑制剂检查了Adam17的整体模型和ADAM17的抑制作用，结果显示代谢健康得到改善，代谢炎症减少。然而，还没有研究使用体内模型来检查脂肪细胞ADAM17的作用。在这项研究中，我们使用与Adam17杂交的表达Adipoq-Cre的小鼠建立了脂肪细胞特异性Adam17基因敲除模型狐狸老鼠。使用此模型，我们显示脂肪细胞ADAM17的丢失在基线代谢反应中没有明显作用。出乎意料的是，在使用高脂饮食（HFD）的代谢应激状态下，我们观察到脂肪细胞ADAM17对代谢表型和炎性细胞群体的总体影响很小。使用全身代谢表型，我们显示，ADAM17的丧失对基线状态以及HFD后的能量利用均没有影响。但是，最后，我们使用高参数流式细胞仪显示，HFD后，脂肪细胞ADAM17的丢失会改变巨噬细胞和嗜酸性粒细胞的数量。总体而言，此处介绍的研究可提供更多关于ADAM17在代谢反应和代谢炎症（尤其是在脂肪细胞中）中的作用的见解。