2. Academic Validation
  3. Alcohol promotes CPT1A-induced lipid metabolism disorder to sentinel-regulate acute pancreatitis

Alcohol promotes CPT1A-induced lipid metabolism disorder to sentinel-regulate acute pancreatitis

  • Eur J Med Res. 2025 Jan 17;30(1):35. doi: 10.1186/s40001-024-02213-8.
Zenghui Li # 1,  Xinghui Li # 1,  Hui Jiang # 2,  Jingdong Li 3,  Bin Xiao 4,  Yong Chen 5,  Shunhai Jian 6,  Mei Zeng 7,  Xiaoming Zhang 8
Affiliations

Affiliations

  • 1 Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Street, Nanchong, 637001, Sichuan, China.
  • 2 School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, 37# Shierqiao Road, Chengdu, 611137, Sichuan, China.
  • 3 Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Street, Nanchong, 637001, Sichuan, China.
  • 4 Department of General Surgery, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, 3# Sanyou South Road, Foshan, 528000, Guangdong, China.
  • 5 Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197# Ruijin Er Road, Shanghai, 200025, China.
  • 6 Department of Pathology, Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Street, Nanchong, 637001, China.
  • 7 Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, 63# Wenhua Road, Nanchong, 637001, Sichuan, China. zengmei123@nsmc.edu.cn.
  • 8 Medical Imaging Key Laboratory of Sichuan Province, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 1# South Maoyuan Street, Nanchong, 637001, Sichuan, China. cjr.zhxm@vip.163.com.
  • # Contributed equally.
PMID: 39819476 DOI: 10.1186/s40001-024-02213-8
Abstract

Background and aims: Previous studies have confirmed that alcohol can increase the sensitivity of the pancreas to stressors and exacerbate the severity of pancreatitis when excessive alcohol intake is combined with Other causes. In the current work, this study attempted to explore how does alcohol regulate cerulein-induced acute pancreatitis, especially before inflammation occurs.

Methods: Proteomics was performed to analyze the differentially expressed proteins in pancreatic tissues from a rat model of pancreatitis. The metabolite levels in the pancreatic tissue, serum of rats and serum of persons with a history of alcohol consumption were detected by LC‒MS/MS. In the present study the impact of etomoxir (a carnitine palmitoyl-transferase 1A-specific inhibitor) treatment on AR42J cells treated with alcohol and the effect of etomoxir injection on the inflammatory response in an alcohol + cerulein-induced AAP rat model was evaluated.

Results: When treated with the same amount of cerulein, the rats that ingested alcohol presented with more severe pancreatitis. The proteomics results revealed that the fatty acid degradation pathway was closely related to the development of alcoholic acute pancreatitis, and CPT1A exhibited the greatest increase (approximately twofold increase). The products (acylcarnitines) of CPT1A were changed in the serum of persons with a history of alcohol consumption. Etomoxir treatment mitigates the influence of alcohol stimulation on the aberrant expression of proteins associated with oxidative stress, increased ROS production, mitochondrial ultrastructural alterations and mitochondrial dysfunction in AR42J cells. Etomoxir injection reduced the inflammatory response in the AAP rat model.

Conclusion: Alcohol upregulates CPT1A protein expression in pancreatic tissue, resulting in abnormal lipid metabolism. The products of lipid metabolism, ROS, contribute to mitochondrial ultrastructural alterations and mitochondrial dysfunction. These changes act as sentinel events that regulate acute pancreatitis.

Keywords

Acute pancreatitis; Lipid metabolism; Mitochondrial dysfunction; Proteomics.

Figures
Products