Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway
Abstract Objective Our 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. Th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Nutrition & Diabetes |
| Online Access: | https://doi.org/10.1038/s41387-022-00202-6 |
| _version_ | 1828496707715858432 |
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| author | Tongtong Qiu Xin Yang Jingzhou Wang Chongge Pan Xiaolong Chu Jianyu Xiong Jianxin Xie Yongsheng Chang Cuizhe Wang Jun Zhang |
| author_facet | Tongtong Qiu Xin Yang Jingzhou Wang Chongge Pan Xiaolong Chu Jianyu Xiong Jianxin Xie Yongsheng Chang Cuizhe Wang Jun Zhang |
| author_sort | Tongtong Qiu |
| collection | DOAJ |
| description | Abstract Objective Our 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. Methods Cells 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. Results In 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). Conclusions Our results indicate that obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 signaling pathway. |
| first_indexed | 2024-12-11T12:34:30Z |
| format | Article |
| id | doaj.art-15629e668e8d48ec86476bd5ece7a5c6 |
| institution | Directory Open Access Journal |
| issn | 2044-4052 |
| language | English |
| last_indexed | 2024-12-11T12:34:30Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Nutrition & Diabetes |
| spelling | doaj.art-15629e668e8d48ec86476bd5ece7a5c62022-12-22T01:07:10ZengNature Publishing GroupNutrition & Diabetes2044-40522022-04-0112111310.1038/s41387-022-00202-6Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathwayTongtong Qiu0Xin Yang1Jingzhou Wang2Chongge Pan3Xiaolong Chu4Jianyu Xiong5Jianxin Xie6Yongsheng Chang7Cuizhe Wang8Jun Zhang9Medical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuMedical College of Shihezi University, Bei-Er-LuAbstract Objective Our 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. Methods Cells 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. Results In 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). Conclusions Our results indicate that obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 signaling pathway.https://doi.org/10.1038/s41387-022-00202-6 |
| spellingShingle | Tongtong Qiu Xin Yang Jingzhou Wang Chongge Pan Xiaolong Chu Jianyu Xiong Jianxin Xie Yongsheng Chang Cuizhe Wang Jun Zhang Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway Nutrition & Diabetes |
| title | Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway |
| title_full | Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway |
| title_fullStr | Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway |
| title_full_unstemmed | Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway |
| title_short | Obesity-induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through GPRs/NF-κB/KLF7 pathway |
| title_sort | obesity induced elevated palmitic acid promotes inflammation and glucose metabolism disorders through gprs nf κb klf7 pathway |
| url | https://doi.org/10.1038/s41387-022-00202-6 |
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