Assistant Professor Miami University Oxford, Ohio, United States
Disclosure(s):
Prachi Wele, BS, MS: No relevant financial relationship(s) with ineligible companies to disclose.
Objectives: Diet-induced obesity is increasing worldwide primarily due to the consumption of Western diet with the majority of fat being saturated fatty acids (SFA). Studies have found that obesity increases the risk of colorectal cancer (CRC) incidence; therefore, the CRC burden is predicted to surge. Interestingly, men are at higher risk of developing CRC throughout life while women possessing estrogen have lower CRC incidence, even though the obesity rate is higher in women than in men. To comprehend these sex-based differences and the role of estrogen in CRC under the influence of an SFA-rich diet, we devised an improved CRC mouse model. We hypothesized that mice fed a SFA-based high-fat diet [HFD (60% fat)] would have larger CRC tumor volume compared to those on a low-fat diet [LFD (10% fat)].
Methods: 4–5-week-old male and female FVB/NJ mice underwent sham surgery [Males (Msham) and Females (Fsham)], while a group of females underwent bilateral ovariectomy (OVX) [Females (FOVX)] to remove the majority of their endogenous estrogen. A week after the surgery, all mice were randomly divided into either LFD or HFD groups, followed by six weekly injections of colon-specific carcinogen azoxymethane [(AOM): 5 mg/kg for week 1 and 10 mg/kg for weeks 2-6)], and cyclically injected 17-beta-estradiol [(E2); 4 µg/ mouse)] to a group of FOVX females [(FOVX+E2)], while the rest of mice received vehicle oil injections, for 22 weeks.
Results: When comparing groups Msham with Fsham and FOVX with FOVX+E2, a general trend of less quantity of food consumption was observed for mice on HFD yet they had a higher body weight, fat mass, and body fat percentage along with significantly larger tumor volumes compared to those on LFD who had higher food consumption.
Conclusions: Factors such as diet-induced obesity, sex hormones, and CRC tumors are rarely studied together, and the current study addresses this research gap to understand CRC and provide better CRC prevention strategies. Future studies include examining diet-induced pro-inflammatory cytokines and adipokines in CRC.
Funding Sources: 1) NIH/NCI R15; 2) Miami University CFR Faculty Research Grants; 3) Miami University's College of Education, Health, and Society Interdisciplinary Research Seed Grant; 4) Sigma Xi Grants in Aid of Research
