Abstract
Objectives
Colorectal cancer (CRC) is one of the most prevalent cancer worldwide. Evidence from epidemiological studies shows that the incidence rate of CRC among elders with age ≥ 50 years is gradually decreased, whereas the rate continuously rise in adults with age < 50 years. Along with the rise of CRC in young adults, a significantly increasing trend in obesity is also observed in youth. The present study aims to investigate how the early-life nutrition influences the intestinal tumorigenesis later in mouse with an age equivalent to an age < 50 years in human.
Methods
APC1638N mice (4 weeks of age) were fed a low-fat diet (N = 22; LF: 10% kcal from fat) or a high-fat diet (N = 23; HF: 60% kcal from fat) for 8 weeks, which is equivalent to child/adolescent age in humans. After that, all animals were switched to standard chow
diet (LabDiet #5P76) and fed for additional 12 weeks before sacrifice. Tumors were examined and the expression tumorigenic Wnt-signaling downstream genes (Cyclin D1, c-Myc and Axin 2) in the intestine were assessed.
Results
Our results showed that compared to LF group, the body weight of both male and female mice significantly increased after 8-week HF feeding (P < 0.05). After switching to the standard chow diet for further 12 weeks feeding, the increase of body weight in HF group remained, although the degree of magnitude reduced, and a statistical significance only shown in female mice (P < 0.05). There were a higher tumor incidence (P = 0.051) and tumor multiplicity (P < 0.05) in males than female. No interactions between gender and diet were observed. The HF group had a higher tumor incidence (P = 0.088) and tumor size (P < 0.05) when compared to the LF group. The expression of Wnt-signaling downstream gene, c-Myc, was significantly increased in the HF group at 24-week of age (P < 0.01).
Conclusions
A short term of high-fat diet in early life tends to promote intestinal tumorigenesis in adults as indicated by a mild increase in tumor incidence and a significant increase in tumor size.
Funding Sources
This project was supported by the US Department of Agriculture Hatch funding (#1013548).