Obesity and Pancreatic Cancer: Insight into Mechanisms

被引：41

作者：

Eibl, Guido ^{[1
]}

Rozengurt, Enrique ^{[2
]}

机构：

[1] UCLA, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA

[2] UCLA, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA

来源：

CANCERS | 2021年 / 13卷 / 20期

基金：

美国国家卫生研究院;

关键词：

obesity; pancreatic cancer; adipose tissue; intrapancreatic fat; inflammation; adipokine; gut microbiome; PROTEIN-COUPLED RECEPTOR; VISCERAL ADIPOSE-TISSUE; GELATINASE-ASSOCIATED LIPOCALIN; DIET-INDUCED OBESITY; BODY-MASS INDEX; NF-KAPPA-B; ONCOGENIC KRAS; HIGH-FAT; METABOLIC ENDOTOXEMIA; DUCTAL ADENOCARCINOMA;

D O I：

10.3390/cancers13205067

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Simple Summary:& nbsp;Obesity is recognized as a chronic progressive disease and risk factor for many human diseases. The high and increasing number of obese people may underlie the expected increase in pancreatic cancer cases in the United States. There are several pathways discussed that link obesity with pancreatic cancer. Adipose tissue and adipose tissue-released factors may thereby play an important role. This review discusses selected mechanisms that may accelerate pancreatic cancer development in obesity.</p> The prevalence of obesity in adults and children has dramatically increased over the past decades. Obesity has been declared a chronic progressive disease and is a risk factor for a number of metabolic, inflammatory, and neoplastic diseases. There is clear epidemiologic and preclinical evidence that obesity is a risk factor for pancreatic cancer. Among various potential mechanisms linking obesity with pancreatic cancer, the adipose tissue and obesity-associated adipose tissue inflammation play a central role. The current review discusses selected topics and mechanisms that attracted recent interest and that may underlie the promoting effects of obesity in pancreatic cancer. These topics include the impact of obesity on KRAS activity, the role of visceral adipose tissue, intrapancreatic fat, adipose tissue inflammation, and adipokines on pancreatic cancer development. Current research on lipocalin-2, fibroblast growth factor 21, and Wnt5a is discussed. Furthermore, the significance of obesity-associated insulin resistance with hyperinsulinemia and obesity-induced gut dysbiosis with metabolic endotoxemia is reviewed. Given the central role that is occupied by the adipose tissue in obesity-promoted pancreatic cancer development, preventive and interceptive strategies should be aimed at attenuating obesity-associated adipose tissue inflammation and/or at targeting specific molecules that mechanistically link adipose tissue with pancreatic cancer in obese patients.</p>

引用

页数：21

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