Obesity, which is an epidemic in the United States, increases the risk of developing cancer. Recently, it has been determined that obesity is associated with chronic low-grade inflammation that requires elements of the immune system. In our preliminary data we find that obese people have a Thelper (TH)22/TH17 signature in blood and adipose tissue, most likely linked to the ongoing inflammation. Interleukin-22 (IL-22) has important proliferative and wound-healing properties on epithelial and stromal cells necessary to maintain homeostasis at mucosal sites. However, we postulate that persistent IL-22 secretion may drive uncontrolled epithelial proliferation and tumor development. IL-22 in adaptive and innate cells is under the control of a transcription factor known as Aryl Hydrocarbon Receptor (AHR). AHR signaling is activated by endogenous ligands but also by diet-associated compounds and environmental products. We plan to test the hypothesis that AHR signaling may favor cancer development in obesity by potentiating IL-22 production. These studies may open new avenues of therapeutic intervention through diet to prevent cancer associated to obesity.

Public Health Relevance

Obesity is constantly rising in the United States and soon 20% of the adult population will be obese. Obesity has devastating consequences on people general health. Obesity increases the risk of diabetes, heart disease, and atherosclerosis and increases the chances of developing cancer. In the last years it became evident that white cells of the blood and organs, which normally fight viral and bacterial infections, are also important to attenuate or worsen obesity and its consequences. In this grant application we propose to study whether a new recently discovered pathway modulating the secretion of some soluble mediators from white blood cells is involved in obesity. We hypothesize that this pathway that detects environmental triggers, in the context of a high calorie, high fat Western diet aggravates obesity and obesity-associated risk of developing cancer.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA176695-02
Application #
8708007
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Program Officer
Johnson, Ronald L
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130