BACH1 controls hepatic insulin signaling and glucose homeostasis in mice
Abstract Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatoc...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44088-z |
| _version_ | 1797376886810083328 |
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| author | Jiayu Jin Yunquan He Jieyu Guo Qi Pan Xiangxiang Wei Chen Xu Zhiyuan Qi Qinhan Li Siyu Ma Jiayi Lin Nan Jiang Jinghua Ma Xinhong Wang Lindi Jiang Qiurong Ding Elena Osto Xiuling Zhi Dan Meng |
| author_facet | Jiayu Jin Yunquan He Jieyu Guo Qi Pan Xiangxiang Wei Chen Xu Zhiyuan Qi Qinhan Li Siyu Ma Jiayi Lin Nan Jiang Jinghua Ma Xinhong Wang Lindi Jiang Qiurong Ding Elena Osto Xiuling Zhi Dan Meng |
| author_sort | Jiayu Jin |
| collection | DOAJ |
| description | Abstract Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor β (IR-β), and loss of BACH1 reduces the interaction between PTP1B and IR-β upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis. |
| first_indexed | 2024-03-08T19:45:03Z |
| format | Article |
| id | doaj.art-0808983d7e5640c3b2950fbb7a889718 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T19:45:03Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-0808983d7e5640c3b2950fbb7a8897182023-12-24T12:22:59ZengNature PortfolioNature Communications2041-17232023-12-0114111910.1038/s41467-023-44088-zBACH1 controls hepatic insulin signaling and glucose homeostasis in miceJiayu Jin0Yunquan He1Jieyu Guo2Qi Pan3Xiangxiang Wei4Chen Xu5Zhiyuan Qi6Qinhan Li7Siyu Ma8Jiayi Lin9Nan Jiang10Jinghua Ma11Xinhong Wang12Lindi Jiang13Qiurong Ding14Elena Osto15Xiuling Zhi16Dan Meng17Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Pathology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityCAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of SciencesDivision of Physiology and Pathophysiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of GrazDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan UniversityAbstract Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor β (IR-β), and loss of BACH1 reduces the interaction between PTP1B and IR-β upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.https://doi.org/10.1038/s41467-023-44088-z |
| spellingShingle | Jiayu Jin Yunquan He Jieyu Guo Qi Pan Xiangxiang Wei Chen Xu Zhiyuan Qi Qinhan Li Siyu Ma Jiayi Lin Nan Jiang Jinghua Ma Xinhong Wang Lindi Jiang Qiurong Ding Elena Osto Xiuling Zhi Dan Meng BACH1 controls hepatic insulin signaling and glucose homeostasis in mice Nature Communications |
| title | BACH1 controls hepatic insulin signaling and glucose homeostasis in mice |
| title_full | BACH1 controls hepatic insulin signaling and glucose homeostasis in mice |
| title_fullStr | BACH1 controls hepatic insulin signaling and glucose homeostasis in mice |
| title_full_unstemmed | BACH1 controls hepatic insulin signaling and glucose homeostasis in mice |
| title_short | BACH1 controls hepatic insulin signaling and glucose homeostasis in mice |
| title_sort | bach1 controls hepatic insulin signaling and glucose homeostasis in mice |
| url | https://doi.org/10.1038/s41467-023-44088-z |
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