KLF7 通过激活 PKCζ/NF-κB 通路促进脂肪细胞炎症和糖代谢紊乱。
KLF7 promotes adipocyte inflammation and glucose metabolism disorder by activating the PKCζ/NF-κB pathway.
机构信息
Department of Medical Genetics, Medical College of Shihezi University, Shihezi, China.
Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.
出版信息
FASEB J. 2023 Jul;37(7):e23033. doi: 10.1096/fj.202300005R.
In the obesity context, inflammatory cytokines secreted by adipocytes lead to insulin resistance and are key to metabolic syndrome development. In our previous study, we found that the transcription factor KLF7 promoted the expression of p-p65 and IL-6 in adipocytes. However, the specific molecular mechanism remained unclear. In the present study, we found that the expression of KLF7, PKCζ, p-IκB, p-p65, and IL-6 in epididymal white adipose tissue (Epi WAT) in mice fed a high-fat diet (HFD) was significantly increased. In contrast, the expression of PKCζ, p-IκB, p-p65, and IL-6 was significantly decreased in Epi WAT of KLF7 fat conditional knockout mice. In 3T3-L1 adipocytes, KLF7 promoted the expression of IL-6 via the PKCζ/NF-κB pathway. In addition, we performed luciferase reporter and chromatin immunoprecipitation assays, which confirmed that KLF7 upregulated the expression of PKCζ transcripts in HEK-293T cells. Collectively, our results show that KLF7 promotes the expression of IL-6 by upregulating PKCζ expression and activating the NF-κB signaling pathway in adipocytes.
在肥胖背景下，脂肪细胞分泌的炎性细胞因子导致胰岛素抵抗，是代谢综合征发展的关键。在我们之前的研究中，我们发现转录因子 KLF7 促进了脂肪细胞中 p-p65 和 IL-6 的表达。然而，具体的分子机制尚不清楚。本研究发现，高脂饮食喂养的小鼠附睾白色脂肪组织（Epi WAT）中 KLF7、PKCζ、p-IκB、p-p65 和 IL-6 的表达明显增加。相反，KLF7 脂肪条件性敲除小鼠的 Epi WAT 中 PKCζ、p-IκB、p-p65 和 IL-6 的表达明显降低。在 3T3-L1 脂肪细胞中，KLF7 通过 PKCζ/NF-κB 通路促进了 IL-6 的表达。此外，我们进行了荧光素酶报告基因和染色质免疫沉淀测定，证实 KLF7 在 HEK-293T 细胞中上调了 PKCζ 转录本的表达。综上所述，我们的研究结果表明，KLF7 通过上调 PKCζ 的表达并激活脂肪细胞中的 NF-κB 信号通路，促进了 IL-6 的表达。
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