The role of ghrelin and leptin in intra-pancreatic fat deposition

Abstract

Obesity, as identified by body mass index (BMI), is a global epidemic. There has been emerging evidence on abdominal obesity playing a role in metabolic disease, which in turn increases the risk of developing many non-communicable diseases (most significantly diabetes mellitus type-2). Recently, ectopic fat accumulations within parenchymatous organs such as the liver and the pancreas have been gaining a lot of research attention. While there has been an extensive investigation on fatty liver as a predisposition to many chronic illnesses, having a fatty pancreas only recently gained more research attention. Leptin and ghrelin, two key players in appetite regulation, have been found to play a role on body fat accumulation. This thesis aims to investigate the association of these two hormones on intra-pancreatic fat in the context of acute pancreatitis. A total of 94 AP patients were recruited, and linear regression analyses were completed across several models that were unadjusted and adjusted for patient- and pancreatitis-related factors during both fasting states and postprandially. The results of this thesis demonstrated that leptin and leptin/ghrelin ratio were significantly associated with intra-pancreatic fat accumulation across all adjusted models during fasting states. Leptin was found to be positively correlated with intra-pancreatic fat deposition postprandially with an adjusted model for age and sex. There was no association found between ghrelin and intra-pancreatic fat accumulation during both fasting and postprandial states. This thesis provides insights into the role of leptin and ghrelin in intra-pancreatic fat accumulation, thus pancreatitis pathophysiology. Additionally, it provides the first investigation of ghrelin and leptin/ghrelin ratio in the context of acute pancreatitis using Magnetic Resonance Imaging-derived quantification of intrapancreatic fat. This thesis builds upon current understanding of AP as a disease and paves the way for future studies of leptin and ghrelin within and beyond the field of pancreatology.