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The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.

Publication ,  Journal Article
Farooq, A; Richman, CM; Swain, SM; Shahid, RA; Vigna, SR; Liddle, RA
Published in: Gastroenterology
September 2021

BACKGROUND & AIMS: Heavy alcohol consumption is a common cause of acute pancreatitis; however, alcohol abuse does not always result in clinical pancreatitis. As a consequence, the factors responsible for alcohol-induced pancreatitis are not well understood. In experimental animals, it has been difficult to produce pancreatitis with alcohol. Clinically, alcohol use predisposes to hypophosphatemia, and hypophosphatemia has been observed in some patients with acute pancreatitis. Because of abundant protein synthesis, the pancreas has high metabolic demands, and reduced mitochondrial function leads to organelle dysfunction and pancreatitis. We proposed, therefore, that phosphate deficiency might limit adenosine triphosphate synthesis and thereby contribute to alcohol-induced pancreatitis. METHODS: Mice were fed a low-phosphate diet (LPD) before orogastric administration of ethanol. Direct effects of phosphate and ethanol were evaluated in vitro in isolated mouse pancreatic acini. RESULTS: LPD reduced serum phosphate levels. Intragastric administration of ethanol to animals maintained on an LPD caused severe pancreatitis that was ameliorated by phosphate repletion. In pancreatic acinar cells, low-phosphate conditions increased susceptibility to ethanol-induced cellular dysfunction through decreased bioenergetic stores, specifically affecting total cellular adenosine triphosphate and mitochondrial function. Phosphate supplementation prevented ethanol-associated cellular injury. CONCLUSIONS: Phosphate status plays a critical role in predisposition to and protection from alcohol-induced acinar cell dysfunction and the development of acute alcohol-induced pancreatitis. This finding may explain why pancreatitis develops in only some individuals with heavy alcohol use and suggests a potential novel therapeutic approach to pancreatitis. Finally, an LPD plus ethanol provides a new model for studying alcohol-associated pancreatic injury.

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Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

September 2021

Volume

161

Issue

3

Start / End Page

982 / 995.e2

Location

United States

Related Subject Headings

  • Tissue Culture Techniques
  • Severity of Illness Index
  • Phosphates
  • Pancreatitis, Alcoholic
  • Pancreas
  • Mitochondria
  • Mice, Inbred C57BL
  • Male
  • Hypophosphatemia
  • Gastroenterology & Hepatology
 

Citation

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Farooq, A., Richman, C. M., Swain, S. M., Shahid, R. A., Vigna, S. R., & Liddle, R. A. (2021). The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis. Gastroenterology, 161(3), 982-995.e2. https://doi.org/10.1053/j.gastro.2021.05.048
Farooq, Ahmad, Courtney M. Richman, Sandip M. Swain, Rafiq A. Shahid, Steven R. Vigna, and Rodger A. Liddle. “The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.Gastroenterology 161, no. 3 (September 2021): 982-995.e2. https://doi.org/10.1053/j.gastro.2021.05.048.
Farooq A, Richman CM, Swain SM, Shahid RA, Vigna SR, Liddle RA. The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis. Gastroenterology. 2021 Sep;161(3):982-995.e2.
Farooq, Ahmad, et al. “The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis.Gastroenterology, vol. 161, no. 3, Sept. 2021, pp. 982-995.e2. Pubmed, doi:10.1053/j.gastro.2021.05.048.
Farooq A, Richman CM, Swain SM, Shahid RA, Vigna SR, Liddle RA. The Role of Phosphate in Alcohol-Induced Experimental Pancreatitis. Gastroenterology. 2021 Sep;161(3):982-995.e2.
Journal cover image

Published In

Gastroenterology

DOI

EISSN

1528-0012

Publication Date

September 2021

Volume

161

Issue

3

Start / End Page

982 / 995.e2

Location

United States

Related Subject Headings

  • Tissue Culture Techniques
  • Severity of Illness Index
  • Phosphates
  • Pancreatitis, Alcoholic
  • Pancreas
  • Mitochondria
  • Mice, Inbred C57BL
  • Male
  • Hypophosphatemia
  • Gastroenterology & Hepatology