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Non-alcoholic fatty pancreas disease (NAFPD) as a pre-neoplastic niche: Metabolic and inflammatory Gateways to pancreatic ductal adenocarcinoma
Author: Hope Onohuean, Kasim Sakran Abass, Ngozi F. Nnolum-Orji, Sarad Pawar Naik Bukke, Abdullateef Isiaka Alagbonsi, Yahya E. Choonara
Publisher: Journal of Clinical & Translational Endocrinology
Published: 2025
Section: School of Pharmacy
Abstract
Non-alcoholic fatty pancreas disease (NAFPD), marked by ectopic triglyceride accumulation in the exocrine
pancreas, is increasingly observed yet its recognition as a cancer-predisposing condition remains limited. We
synthesize evidence supporting NAFPD as an early and modifiable niche for pancreatic ductal adenocarcinoma
(PDAC), using a PRISMA-ScR-guided framework. The findings were synthesized into three domains: epidemio
logical risk, metabolic–inflammatory signaling, and immune–stromal remodeling. Mechanisms include
palmitate-induced ER stress, ROS-driven NLRP3–IL-1β and STAT5 signaling, and KRAS^G12D-mediated lip
otoxicity. Lipid-laden stellate cells promote fibrosis, immunosuppression, and epithelial–mesenchymal transi
tion. NAFPD may represent an early, modifiable PDAC niche, warranting further imaging–omic studies and
targeted prevention trials.