Obesity-Induced Adipose Tissue Inflammation as a Strong Promotional Factor for Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is expected to soon become the second leading cause of cancer related deaths in the United States. This may be due to the rising obesity prevalence, which is a recognized risk factor for PDAC. There is great interest in deciphering the underlying driving mechanisms of the obesity-PDAC link. Visceral adiposity has a strong correlation to certain metabolic diseases and gastrointestinal cancers, including PDAC. In fact, our own data strongly suggest that visceral adipose tissue inflammation is a strong promoter for PDAC growth and progression in a genetically engineered mouse model of PDAC and diet-induced obesity. In this review, we will discuss the relationship between obesity-associated adipose tissue inflammation and PDAC development, with a focus on the key molecular and cellular components in the dysfunctional visceral adipose tissue, which provides a tumor permissive environment.

Keywords: adipose tissue inflammation; obesity; pancreatic ductal adenocarcinoma.

Figure 1

Representative histology of mesenteric adipose tissue of conditional KrasG12D mice fed an obesogenic high fat high calorie diet (HFCD) for 3 months supplemented without (upper panel) or with simvastatin (sim; lower panel). Quantification of crown-like structures demonstrates significant elevation of adipose tissue inflammation in obese HFCD-fed mice, which was abrogated by simvastatin (sim). *: p < 0.01 vs. CD; #: p < 0.01 vs. HFCD