Transcriptome profile of peripancreatic adipose tissue in pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disease marked by extensive fibrosis that ultimately impairs both exocrine and endocrine pancreatic function. Obesity is a known risk factor, and patients with CP often exhibit increased visceral adiposity, including fat infiltration around and within the pancreas. The specific contribution of peripancreatic adipose tissue (PAT), which lies in direct contact with the pancreas, to pancreatitis inflammation and diabetes remains unclear. Using bulk and single-nuclei RNA sequencing, this study analyzed PAT from organ donors with CP or a history of resolved acute pancreatitis (HAP), comparing them to non-pancreatitis controls with or without diabetes. Over 1000 genes were dysregulated in the groups with pancreatitis relative to controls, particularly those involved in adipogenesis and fatty acid metabolism, indicating PAT expansion. CP-associated PAT showed greater inflammation and fibrosis than HAP. Interestingly, diabetes in pancreatitis was linked to a comparatively healthier PAT profile, possibly reflecting cohort differences. Network analysis further revealed that pancreatic fibrosis correlated with inflamed, extracellular matrix–enriched PAT. Donors with fatty pancreas exhibited more PAT inflammation and reduced lymphatic endothelial activation. Overall, PAT characteristics appear closely linked to pancreatic fibrosis and fat accumulation, potentially leading to deterioration in pancreatic function.