The Fat-Pancreas Axis: A Narrative Review Unraveling the Role of Obesity in Pancreatic Diseases.

Abstract

Obesity has alarmingly risen across the globe as a significant public health concern and is increasingly recognized as a complex systemic disease with widespread metabolic and inflammatory consequences. While its associations with cardiovascular, hepatic, and metabolic disorders are well established, the impact of obesity on the pancreas has received comparatively less attention. Emerging evidence highlights that pancreatic steatosis is closely linked to obesity, type 2 diabetes, metabolic syndrome, and fatty liver disease. Fatty pancreas contributes to both endocrine and exocrine dysfunction through lipotoxicity, oxidative stress, and adipokine-mediated inflammation. In acute pancreatitis, obesity exacerbates disease severity by amplifying systemic inflammatory responses, promoting lipolysis of peripancreatic fat, and delaying immune resolution, all of which increase complications and mortality. The role of obesity in chronic pancreatitis is less defined, though intrapancreatic fat accumulation appears to predispose to parenchymal injury and progression. Obesity is increasingly considered an independent risk factor for pancreatic cancer, with excess adiposity driving neoplastic transformation through chronic inflammation, insulin resistance, hyperinsulinemia, and activation of oncogenic pathways. Weight reduction is associated with reduced pancreatic steatosis and may lower risk; however, causal data are limited, and further longitudinal studies are required. Taken together, obesity represents a major modifiable determinant of pancreatic health, with implications spanning steatosis, inflammatory diseases, and malignancy. Increasing scientific data on the obesity-pancreatic diseases conundrum also necessitates the need for integrating obesity-related markers into risk stratification and prognostic models, as well as exploring targeted therapeutic strategies in obesity-associated pancreatic disease.