TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice
Abstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in...
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| Format: | Article |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-08319-w |
| _version_ | 1818754217708355584 |
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| author | Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh |
| author_facet | Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh |
| author_sort | Jong Youl Lee |
| collection | DOAJ |
| description | Abstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice. Here, mice were fed a high-fat diet (HFD) for 16 weeks and received an intraperitoneal injection of 100 mg/kg streptozotocin (STZ) and followed by continued HFD feeding for an additional 4 weeks to induce hyperglycemia and hepatic steatosis. Compared with wild-type diabetic mice, diabetic TonEBP+/− mice showed decreased body weight, fat mass, hepatic steatosis, and macrophage infiltration. We also found that adipogenesis and HMGB1 expression in the liver and hippocampus were lower in diabetic TonEBP+/− mice compared with the wild type. Furthermore, iba-1 immunoreactivity in the hippocampus was decreased in diabetic TonEBP+/− mice compared with that in the wild type. Our findings suggest that TonEBP haploinsufficiency suppresses diabetes-associated hepatic steatosis and neuroinflammation. |
| first_indexed | 2024-12-18T05:19:45Z |
| format | Article |
| id | doaj.art-ec10050aa8ec4c0993ff33816e9eaeeb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:19:45Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ec10050aa8ec4c0993ff33816e9eaeeb2022-12-21T21:19:41ZengNature PortfolioScientific Reports2045-23222017-08-017111010.1038/s41598-017-08319-wTonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic miceJong Youl Lee0Eun Ae Jeong1Kyung Eun Kim2Chin-ok Yi3Zhen Jin4Jung Eun Lee5Dong Hoon Lee6Hyun Joon Kim7Sang Soo Kang8Gyeong Jae Cho9Wan Sung Choi10Soo Youn Choi11H. Moo Kwon12Gu Seob Roh13Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Thoracic and Cardiovascular Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine, JinjuDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineSchool of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and TechnologySchool of Nano-Biotechnology and Chemical Engineering, Ulsan National Institute of Science and TechnologyDepartment of Anatomy and Convergence Medical Science, Institute of Health Sciences, Gyeongsang National University School of MedicineAbstract Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice. Here, mice were fed a high-fat diet (HFD) for 16 weeks and received an intraperitoneal injection of 100 mg/kg streptozotocin (STZ) and followed by continued HFD feeding for an additional 4 weeks to induce hyperglycemia and hepatic steatosis. Compared with wild-type diabetic mice, diabetic TonEBP+/− mice showed decreased body weight, fat mass, hepatic steatosis, and macrophage infiltration. We also found that adipogenesis and HMGB1 expression in the liver and hippocampus were lower in diabetic TonEBP+/− mice compared with the wild type. Furthermore, iba-1 immunoreactivity in the hippocampus was decreased in diabetic TonEBP+/− mice compared with that in the wild type. Our findings suggest that TonEBP haploinsufficiency suppresses diabetes-associated hepatic steatosis and neuroinflammation.https://doi.org/10.1038/s41598-017-08319-w |
| spellingShingle | Jong Youl Lee Eun Ae Jeong Kyung Eun Kim Chin-ok Yi Zhen Jin Jung Eun Lee Dong Hoon Lee Hyun Joon Kim Sang Soo Kang Gyeong Jae Cho Wan Sung Choi Soo Youn Choi H. Moo Kwon Gu Seob Roh TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice Scientific Reports |
| title | TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice |
| title_full | TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice |
| title_fullStr | TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice |
| title_full_unstemmed | TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice |
| title_short | TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice |
| title_sort | tonebp nfat5 haploinsufficiency attenuates hippocampal inflammation in high fat diet streptozotocin induced diabetic mice |
| url | https://doi.org/10.1038/s41598-017-08319-w |
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