Association between intra-pancreatic fat deposition and diseases of the exocrine pancreas: A narrative review

Figure 1 Mechanism of intrapancreatic fat deposition-induced pancreatitis. In intrapancreatic fat deposition, chronic endogenous tissue stress and dysfunction initiate a persistent inflammatory response. Over time, this inflammation escalates, eventually manifesting as clinically significant acute pancreatitis. Additionally, adipokines secreted from adipose tissue surrounding the pancreas further exacerbate systemic inflammation. IPFD: Intrapancreatic fat deposition; AP: Acute pancreatitis.

Figure 2 Mechanism of intrapancreatic fat deposition-induced pancreatic cancer. During intrapancreatic fat deposition, the accumulation of intracellular lipid droplets leads to an elevation in toxic free fatty acids, which induces mitochondrial dysfunction and triggers the unfolded protein response. These events contribute to the development of pancreatic cancer. Moreover, pro-inflammatory cytokines and cytotoxic fatty acids released by pancreatic adipocytes in the intrapancreatic fat deposition environment foster an inflammatory microenvironment. This microenvironment facilitates the proliferation of transformed cells with carcinogenic potential by promoting the recruitment of tumor-supportive immune cells. IPFD: Intrapancreatic fat deposition; PDAC: Pancreatic ductal adenocarcinoma; FFA: Free fatty acid.

Figure 3 Therapeutic mechanism of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in intrapancreatic fat deposition. Glucagon-like peptide-1 receptor agonists potentially mitigate intrapancreatic fat deposition and its complications by modulating the endoplasmic reticulum stress pathway and downstream apoptosis signaling. In contrast, dipeptidyl peptidase-4 inhibitors exert therapeutic effects by regulating adipokines - such as reducing tumor necrosis factor-α levels and enhancing adiponectin production - and by modulating intracellular lipid droplet content. IPFD: Intrapancreatic fat deposition; GLP-1: Glucagon-like peptide-1; DPP-4: Dipeptidyl peptidase-4; TNF: Tumor necrosis factor.