The Influence of High-Fat Diet in Early Life on Intestinal Tumorigenesis in APC1638N Mice
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).