Dysregulated pancreatic lipid phenotype, inflammation and cellular injury in a chronic ethanol feeding model of hepatic alcohol dehydrogenase-deficient deer mice

Mukund Prathivadibhayankaram, Kamlesh K. Bhopale, Anna A. Caracheo, Lata Kaphalia, Vsevolod Popov, Paul J. Boor, Bhupendra S. Kaphalia

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Dysregulation of pancreatic fat and lipotoxic inflammation are common clinical findings in alcoholic chronic pancreatitis (ACP). In this study, we investigated a relationship between dysregulated pancreatic lipid metabolism and the development of injury in a chronic ethanol (EtOH) feeding model of hepatic alcohol dehydrogenase 1- deficient (ADH) deer mice. Methods: ADH and hepatic ADH normal (ADH+) deer mice were fed a liquid diet containing 3 % EtOH for three months and received a single gavage of binge EtOH with/without fatty acid ethyl esters (FAEEs) one week before the euthanasia. Plasma and pancreatic tissue were analyzed for lipids including FAEEs, inflammatory markers and adipokines using GC–MS, bioassays/kits, and immunostaining, respectively. Pancreatic morphology and proteins involved in lipogenesis were determined by the H & E staining, electron microscopy and Western blot analysis. Key findings: Chronic EtOH feeding in ADH vs. ADH+ deer mice resulted in a significant increase in the levels of pancreatic lipids including FAEEs, adipokines (leptin and resistin), fat infiltration with inflammatory cells and lipid droplet deposition along with the proteins involved in lipogenesis. The changes exacerbated by an administration of binge EtOH with/without FAEEs in the pancreas of ADH vs. ADH+ deer mice fed chronic EtOH suggest a metabolic basis for ACP. Significance: These findings suggest that the liver-pancreatic axis plays a crucial role in etiopathogenesis of ACP, as the increased body burden of EtOH due to hepatic ADH deficiency exacerbates pancreatic injury.

Original languageEnglish (US)
Article number121670
JournalLife Sciences
Volume322
DOIs
StatePublished - Jun 1 2023

Keywords

  • Alcoholic chronic pancreatitis
  • AMPKα signaling
  • Deer mice
  • Fatty acid ethyl esters
  • Lipid metabolism
  • Pancreatic interstitial fatty inflammation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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