Treadmill Exercise Decreases Aberrant Crypt Foci Lymph Associated in the Large Intestine of Obese Mice

Abstract

Colorectal cancer is the third leading cancer for both incidence and mortality. Obesity increases risk of developing colorectal cancer. On the other hand, increased physical activity is associated with a decreased risk of a variety of cancers. However, mechanisms of how physical activity reduces risk of cancer development remain to be illustrated. We hypothesize that exercise reduces the risk of developing colon cancer in obese animals. The aim of our study was to understand how diet and exercise affect metabolism and colon cancer formation in a preclinical model. To test this, C57BL/6N mice were fed either a control diet, AIN‐93M, or a high fat (HF) diet consisting of 45% fat for 9 weeks followed by intraperitoneal injection of carcinogen Azoxymethane (AOM). Mice on HF diet were divided into two groups: high‐fat (HF) and high‐fat plus exercise (HF+EX). A 24‐week progressive treadmill‐training program (1 hr/d, 3 d/wk) was used to exercise the mice in the HF+EX group. At the end of the study, all colons were sampled for histological examination of aberrant crypt foci (ACF) development by methylene blue staining. As expected the HF group had more ACF compared to the control group (5.29 vs 3.93, p < 0.05), but was not statistically different from the HF+EX group (5.29 vs 6.11, p = 0.23). Interestingly, the HF+EX group had more lymph nodules in the colon epithelial surface than the HF and control group (37, 17, and 12, respectively, p < 0.05). This led to the observation that ACF found around lymphatic tissue were significantly less in the exercised HF+EX group compared to the non‐exercised HF group (0.25 vs 0.61, p < 0.05). In addition, qRT‐PCR analysis of gene expression in the liver showed that cMYC expression was lower in the HF+EX group compared to both the HF and control groups. Since cMYC is an oncogene that plays a role in glucose metabolism, mitochondrial biogenesis, lipid synthesis, and ribosome biogenesis, further analysis is done to determine the involvement of the various pathways in this mouse model of colon cancer. In summary, data from this study indicate that exercise may play a protective role in colon cancer development by increasing activity of the immune response through the development of lymphatic system in the colon and reducing the potential of ACF formation.