Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway.
Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway.
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肥胖引起的棕榈酸升高通过 GPRs/NF-κB/KLF7 通路促进炎症和糖代谢紊乱
DOI：
10.1038/s41387-022-00202-6
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发表时间：
2022-04-20
影响因子：
6.1
通讯作者：
Zhang, Jun
中科院分区：
文献类型：
--
作者：
Qiu, Tongtong;Yang, Xin;Wang, Jingzhou;Pan, Chongge;Chu, Xiaolong;Xiong, Jianyu;Xie, Jianxin;Chang, Yongsheng;Wang, Cuizhe;Zhang, Jun
我们以往的研究表明，肥胖诱导的过量棕榈酸(PA)可以促进KLF7的表达，KLF7在调节炎症、糖代谢方面起着至关重要的作用。但PA上调KLF7表达的确切机制尚不清楚。本研究旨在探讨PA是否通过Gprs/NF-κB信号通路促进KLF7的表达，从而导致炎症和糖代谢紊乱。方法体外在PA刺激下阻断细胞Gprs/NF-κB，以阐明PA上调KLF7表达的分子机制。通过荧光素酶报告基因检测p65对KLF7的调控作用。结果在3T3-L1脂肪细胞和肝癌细胞中，PA可通过促进GPR40/120-NF-κB信号通路上调KLF7的表达，从而导致炎症反应，减少葡萄糖消耗(p<；均为 0.05)。荧光素酶报告基因检测和芯片检测表明，p65能在转录水平上上调KLF7的表达。在高脂饮食小鼠，腹腔注射GPR40或GPR120阻滞剂后，附睾白脂肪组织和肝脏中p-P65和KLF7的水平均显著降低(p<； 均为0.05)。药物抑制p-p65可显著降低KLF7的表达，改善糖耐量和胰岛素敏感性(p<； 均为0.05)。结论肥胖诱导的棕榈酸升高通过Gprs/NF-κB/KLF7信号通路促进炎症和糖代谢紊乱。
ObjectiveOur previous results have shown that obesity-induced excessive palmitic acid (PA) can promote the expression of KLF7, which plays a vital role in regulation of inflammation, glucose metabolism. But the exact mechanism of PA up-regulating the expression of KLF7 is not clear yet. This study is intend to explore whether PA promoting KLF7 expression through GPRs/NF-κB signaling pathway, causing inflammation and glucose metabolism disorders.MethodsCells were blocked GPRs/NF-κB under PA stimulation in vitro to demonstrate the molecular mechanism of PA up-regulates KLF7 expression. The regulatory effect of p65 on KLF7 was detected by luciferase reporter gene assay. Blocking GPRs/NF-κB in diet-induced obesity mice to detect the expression of KLF7, inflammatory cytokines and glucose metabolism related factors, clarifying the effects of GPRs/NF-κB on KLF7 in vivo.ResultsIn 3T3-L1 adipocytes and HepG2 cells, PA could up-regulate the expression of KLF7 by promoting the GPR40/120-NF-κB signaling pathway, leading to inflammation and reduced glucose consumption (p< 0.05 for both). Luciferase reporter gene assay and ChIP assay showed that p65 could transcriptionally up-regulates the expression of KLF7. In high-fat diet (HFD) mice, after intraperitoneal injection of GPR40 or GPR120 blocker, the levels of p-p65 and KLF7 in epididymal white adipose tissue and liver were significantly decreased (p< 0.05 for both). Pharmacological inhibition of p-p65 significantly attenuated KLF7 expression and improved glucose tolerant and insulin sensitive (p< 0.05 for both).ConclusionsOur results indicate that obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 signaling pathway.
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