Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity
Abstract To investigate the mechanisms behind the worsening of acute lung injury (ALI) in obesity, transcriptomic sequencing is performed, and significantly reduced mRNA levels of Aconitate Decarboxylase 1 (ACOD1) in the lung tissue of high‐fat diet (HFD) mice are found. Clinical samples are collect...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202413546 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849704019169116160 |
|---|---|
| author | Jingyue Ma Yichan Ao Zhen Yue Zhiqiao Wang Xiangyu Hou Hongbin Li Hanbing Wang Siqing Luo Jianyu He Zikun Duan Ling Liu Ke Wei |
| author_facet | Jingyue Ma Yichan Ao Zhen Yue Zhiqiao Wang Xiangyu Hou Hongbin Li Hanbing Wang Siqing Luo Jianyu He Zikun Duan Ling Liu Ke Wei |
| author_sort | Jingyue Ma |
| collection | DOAJ |
| description | Abstract To investigate the mechanisms behind the worsening of acute lung injury (ALI) in obesity, transcriptomic sequencing is performed, and significantly reduced mRNA levels of Aconitate Decarboxylase 1 (ACOD1) in the lung tissue of high‐fat diet (HFD) mice are found. Clinical samples are collected, an ALI model is established in HFD mice, and both human and mouse samples are analyzed, revealing a significant decrease in ACOD1 expression in lung tissue and alveolar macrophages in obesity. Further in vivo and in vitro experiments show that ACOD1 knockdown worsens lung injury, inflammation, and oxidative stress, while ACOD1 overexpression alleviates these effects. Moreover, nuclear factor erythroid 2‐related factor 2 (Nrf2) inhibition diminishes the protective effects of ACOD1 overexpression in ALI exacerbated by obesity. Additionally, in the context of obesity, growth factor independent 1 (GFI1) protein levels are elevated in alveolar macrophages, and its knockdown leads to upregulated ACOD1 expression. Therefore, this study suggests that ACOD1 downregulation in alveolar macrophages is a key factor in worsening ALI in obesity, likely driven by GFI1 upregulation. |
| format | Article |
| id | doaj-art-d5622c0aa5ce44b4ae1ae93d6a20ac0d |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d5622c0aa5ce44b4ae1ae93d6a20ac0d2025-08-20T03:16:56ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202413546Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in ObesityJingyue Ma0Yichan Ao1Zhen Yue2Zhiqiao Wang3Xiangyu Hou4Hongbin Li5Hanbing Wang6Siqing Luo7Jianyu He8Zikun Duan9Ling Liu10Ke Wei11Department of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology Xinjiang Uygur Autonomous Region Changji People's Hospital Changji 831100 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaDepartment of Anesthesiology The First Affiliated Hospital of Chongqing Medical University Chongqing 400016 ChinaAbstract To investigate the mechanisms behind the worsening of acute lung injury (ALI) in obesity, transcriptomic sequencing is performed, and significantly reduced mRNA levels of Aconitate Decarboxylase 1 (ACOD1) in the lung tissue of high‐fat diet (HFD) mice are found. Clinical samples are collected, an ALI model is established in HFD mice, and both human and mouse samples are analyzed, revealing a significant decrease in ACOD1 expression in lung tissue and alveolar macrophages in obesity. Further in vivo and in vitro experiments show that ACOD1 knockdown worsens lung injury, inflammation, and oxidative stress, while ACOD1 overexpression alleviates these effects. Moreover, nuclear factor erythroid 2‐related factor 2 (Nrf2) inhibition diminishes the protective effects of ACOD1 overexpression in ALI exacerbated by obesity. Additionally, in the context of obesity, growth factor independent 1 (GFI1) protein levels are elevated in alveolar macrophages, and its knockdown leads to upregulated ACOD1 expression. Therefore, this study suggests that ACOD1 downregulation in alveolar macrophages is a key factor in worsening ALI in obesity, likely driven by GFI1 upregulation.https://doi.org/10.1002/advs.202413546ACOD1ARDSlung injurymacrophagesobesity |
| spellingShingle | Jingyue Ma Yichan Ao Zhen Yue Zhiqiao Wang Xiangyu Hou Hongbin Li Hanbing Wang Siqing Luo Jianyu He Zikun Duan Ling Liu Ke Wei Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity Advanced Science ACOD1 ARDS lung injury macrophages obesity |
| title | Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity |
| title_full | Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity |
| title_fullStr | Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity |
| title_full_unstemmed | Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity |
| title_short | Elevated GFI1 in Alveolar Macrophages Suppresses ACOD1 Expression and Exacerbates Lipopolysaccharide‐Induced Lung Injury in Obesity |
| title_sort | elevated gfi1 in alveolar macrophages suppresses acod1 expression and exacerbates lipopolysaccharide induced lung injury in obesity |
| topic | ACOD1 ARDS lung injury macrophages obesity |
| url | https://doi.org/10.1002/advs.202413546 |
| work_keys_str_mv | AT jingyuema elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT yichanao elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT zhenyue elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT zhiqiaowang elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT xiangyuhou elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT hongbinli elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT hanbingwang elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT siqingluo elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT jianyuhe elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT zikunduan elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT lingliu elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity AT kewei elevatedgfi1inalveolarmacrophagessuppressesacod1expressionandexacerbateslipopolysaccharideinducedlunginjuryinobesity |