Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt
Abstract Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin’s effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogeno...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-10-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04235-0 |
| _version_ | 1818578849033617408 |
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| author | Wenfang Xiong Kuo-Yang Sun Yan Zhu Xiaoqi Zhang Yi-Hua Zhou Xiaoping Zou |
| author_facet | Wenfang Xiong Kuo-Yang Sun Yan Zhu Xiaoqi Zhang Yi-Hua Zhou Xiaoping Zou |
| author_sort | Wenfang Xiong |
| collection | DOAJ |
| description | Abstract Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin’s effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogenous fatty acid synthesis and the inhibition of fatty acid synthase (FASN) downregulates proinflammatory responses. We further show that metformin could suppress such elevation of FASN as well as proinflammatory activation in macrophages. In vivo, metformin treatment ameliorates dextran sulfate sodium (DSS)-induced colitis through impairing proinflammatory activation of colonic lamina propria mononuclear cells (LPMCs). The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation. Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages. From the perspective of immunometabolism, our work points towards metformin utilization as an effective and potential intervention against macrophages-involved inflammatory diseases. |
| first_indexed | 2024-12-16T06:52:20Z |
| format | Article |
| id | doaj.art-13c50c98e7854f9d9e0504f47399118f |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-16T06:52:20Z |
| publishDate | 2021-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-13c50c98e7854f9d9e0504f47399118f2022-12-21T22:40:22ZengNature Publishing GroupCell Death and Disease2041-48892021-10-01121011510.1038/s41419-021-04235-0Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of AktWenfang Xiong0Kuo-Yang Sun1Yan Zhu2Xiaoqi Zhang3Yi-Hua Zhou4Xiaoping Zou5Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolState Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolDepartment of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical SchoolAbstract Metformin, traditionally regarded as a hypoglycemic drug, has been studied in other various fields including inflammation. The specific mechanism of metformin’s effect on immune cells remains unclear. Herein, it is verified that LPS-induced macrophages are characterized by enhanced endogenous fatty acid synthesis and the inhibition of fatty acid synthase (FASN) downregulates proinflammatory responses. We further show that metformin could suppress such elevation of FASN as well as proinflammatory activation in macrophages. In vivo, metformin treatment ameliorates dextran sulfate sodium (DSS)-induced colitis through impairing proinflammatory activation of colonic lamina propria mononuclear cells (LPMCs). The reduction of FASN by metformin hinders Akt palmitoylation, which further disturbs Akt membrane attachment and its phosphorylation. Metformin-mediated suppression of FASN/Akt pathway and its downstream MAPK signaling contributes to its anti-inflammatory role in macrophages. From the perspective of immunometabolism, our work points towards metformin utilization as an effective and potential intervention against macrophages-involved inflammatory diseases.https://doi.org/10.1038/s41419-021-04235-0 |
| spellingShingle | Wenfang Xiong Kuo-Yang Sun Yan Zhu Xiaoqi Zhang Yi-Hua Zhou Xiaoping Zou Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt Cell Death and Disease |
| title | Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt |
| title_full | Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt |
| title_fullStr | Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt |
| title_full_unstemmed | Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt |
| title_short | Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt |
| title_sort | metformin alleviates inflammation through suppressing fasn dependent palmitoylation of akt |
| url | https://doi.org/10.1038/s41419-021-04235-0 |
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