Establishment and Comparative Analysis of Four Mouse Models for the Study of Pancreatic Steatosis.

Pancreatic steatosis is closely associated with metabolic disorders, pancreatitis, and pancreatic cancer, yet the underlying mechanisms remain incompletely understood and ideal animal models are lacking. We established and compared four mouse models based on distinct pathogenic mechanisms. In the high-fat diet (HFD)-fed model, pancreatic steatosis occurred later than hepatic steatosis. In ob/ob mice, despite severe obesity and hepatic steatosis, no significant intrapancreatic fat deposition was observed. In the caerulein combined with HFD model, caerulein markedly accelerated HFD-induced intrapancreatic fat accumulation, indicating a synergistic effect of inflammation and metabolic stress. Orthotopic injection of adipogenically differentiated 3T3-L1 cells established a focal model without altering systemic metabolism, enabling investigation of localized fat deposition. Collectively, these four models recapitulate metabolic, genetic, inflammatory, and localized mechanisms, exhibit divergent histological features, and provide a complementary platform for mechanistic studies and drug screening in pancreatic steatosis.