Intrapancreatic fat, pancreatitis, and pancreatic cancer

Abstract

Pancreatic cancer is typically detected at an advanced stage, and is refractory to most forms of treatment, contributing to poor survival outcomes. The incidence of pancreatic cancer is gradually increasing, linked to an aging population and increasing rates of obesity and pancreatitis, which are risk factors for this cancer. Sources of risk include adipokine signaling from fat cells throughout the body, elevated levels of intrapancreatic intrapancreatic adipocytes (IPAs), inflammatory signals arising from pancreas-infiltrating immune cells and a fibrotic environment induced by recurring cycles of pancreatic obstruction and acinar cell lysis. Once cancers become established, reorganization of pancreatic tissue typically excludes IPAs from the tumor microenvironment, which instead consists of cancer cells embedded in a specialized microenvironment derived from cancer-associated fibroblasts (CAFs). While cancer cell interactions with CAFs and immune cells have been the topic of much investigation, mechanistic studies of the source and function of IPAs in the pre-cancerous niche are much less developed. Intriguingly, an extensive review of studies addressing the accumulation and activity of IPAs in the pancreas reveals that unexpectedly diverse group of factors cause replacement of acinar tissue with IPAs, particularly in the mouse models that are essential tools for research into pancreatic cancer. Genes implicated in regulation of IPA accumulation include KRAS, MYC, TGF-β, periostin, HNF1, and regulators of ductal ciliation and ER stress, among others. These findings emphasize the importance of studying pancreas-damaging factors in the pre-cancerous environment, and have significant implications for the interpretation of data from mouse models for pancreatic cancer.

Statin Induced Changes in Rat Pancreatic Tissue: A Histological and Biochemical Perspective

“…The inflammation and fatty changes are particularly noteworthy, as they can disturb exocrine and endocrine function. 9 The presence of immune cells and adipocytes in the parenchyma alters the pancreatic microenvironment. This may impair acinar enzyme production and islet hormone secretion, providing a histopathological basis for clinical reports of statininduced pancreatitis and diabetes.…”

Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study

“…In line with the literature, this study also observed a negative association between the measured circulatory abundance of miR-21-3p and that of MR-%IPFD. Since IPFD and pancreatitis are closely associated, the observed negative abundance of miR-21 could possibly be an early indicator of later-life pancreatitis [ 36 , 37 ]. However, to confirm these results, there is an important need to confirm the functionality of these results in animal and cell models.…”

Determining Optimal Cut-Off Value of Pancreatic-Cancer-Induced Total Cholesterol and Obesity-Related Factors for Developing Exercise Intervention: Big Data Analysis of National Health Insurance Sharing Service Data

“…For example, BMI is considered to be an influencing factor, which increases the incidence of leukemia and pancreatic, uterine, and colon cancers [27]. Adipokine-related signals from the intrapancreatic adipocyte exacerbate pancreatitis, which is well established as a risk factor for subsequent development of pancreatic cancer [28].…”