2. Academic Validation
  3. Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt

Metformin alleviates inflammation through suppressing FASN-dependent palmitoylation of Akt

  • Cell Death Dis. 2021 Oct 12;12(10):934. doi: 10.1038/s41419-021-04235-0.
Wenfang Xiong  # 1,  Kuo-Yang Sun  # 2,  Yan Zhu 1,  Xiaoqi Zhang 3,  Yi-Hua Zhou 4,  Xiaoping Zou 5
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China.
  • 3 Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. 13770654281@163.com.
  • 4 Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. zgr03summer@126.com.
  • 5 Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, PR China. zouxp@nju.edu.cn.
  • # Contributed equally.
PMID: 34642298 DOI: 10.1038/s41419-021-04235-0
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.

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