Multi-generational consumption of a Western diet for rodents promotes colitis-associated colorectal cancer in third-generation offspring.
Class
Article
Graduation Year
2018
College
College of Agriculture and Applied Sciences
Department
Animal, Dairy, and Veterinary Sciences Department
Faculty Mentor
Abby Benninghoff
Presentation Type
Oral Presentation
Abstract
The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely consume highly processed foods that are energy- dense and nutrient-poor. The primary objective of this study was to determine the impact of ancestral or multi-generational exposure to the total Western diet (TWD), a Western-style diet formulated for rodents using human US nutrient intake data, in a murine model of inflammation-associated colorectal carcinogenesis. The hypotheses tested were 1) consumption of TWD by F0 parents would promote colitis-associated colorectal cancer (CAC) in F3 generation offspring and 2) consumption of TWD over multiple generations would further exacerbate disease development compared to direct-exposed offspring. C57BL/6J mice were bred for three generations, during which they were fed a standard diet (AIN93G), TWD, or a simple high fat diet (DIO, 45% diet-induced obesity diet) during the F0 generation only, for the duration of F0 through F3 generations, or the F3 generation only. The azoxymethane and dextran sodium sulfate model of CAC was employed in F3 offspring, which were necropsied at 24 weeks of age. Notably, tumor incidence was increased by trans-generational exposure to TWD (92%) when compared to consecutive AIN93G exposure only (56%). Moreover, successive exposure to TWD markedly increased tumor burden (> 3-fold increase) when compared to direct TWD exposure. Alternatively, neither trans-generational nor multi-generational exposure to DIO altered tumor incidence; however, tumor burden was unexpectedly increased in F3 offspring trans-generationally-exposed to the DIO was observed as compared to direct DIO exposure. In summary, ancestral exposure to TWD markedly increased CAC incidence and disease severity in third generation offspring that were not directly fed this diet. Additionally, continuous exposure to TWD over three generations exacerbated disease outcome in third generation offspring as compared to those fed TWD directly.
Location
Room 154
Start Date
4-13-2017 12:00 PM
End Date
4-13-2017 1:15 PM
Multi-generational consumption of a Western diet for rodents promotes colitis-associated colorectal cancer in third-generation offspring.
Room 154
The majority of colorectal cancer cases can be attributed to poor diet, yet Americans routinely consume highly processed foods that are energy- dense and nutrient-poor. The primary objective of this study was to determine the impact of ancestral or multi-generational exposure to the total Western diet (TWD), a Western-style diet formulated for rodents using human US nutrient intake data, in a murine model of inflammation-associated colorectal carcinogenesis. The hypotheses tested were 1) consumption of TWD by F0 parents would promote colitis-associated colorectal cancer (CAC) in F3 generation offspring and 2) consumption of TWD over multiple generations would further exacerbate disease development compared to direct-exposed offspring. C57BL/6J mice were bred for three generations, during which they were fed a standard diet (AIN93G), TWD, or a simple high fat diet (DIO, 45% diet-induced obesity diet) during the F0 generation only, for the duration of F0 through F3 generations, or the F3 generation only. The azoxymethane and dextran sodium sulfate model of CAC was employed in F3 offspring, which were necropsied at 24 weeks of age. Notably, tumor incidence was increased by trans-generational exposure to TWD (92%) when compared to consecutive AIN93G exposure only (56%). Moreover, successive exposure to TWD markedly increased tumor burden (> 3-fold increase) when compared to direct TWD exposure. Alternatively, neither trans-generational nor multi-generational exposure to DIO altered tumor incidence; however, tumor burden was unexpectedly increased in F3 offspring trans-generationally-exposed to the DIO was observed as compared to direct DIO exposure. In summary, ancestral exposure to TWD markedly increased CAC incidence and disease severity in third generation offspring that were not directly fed this diet. Additionally, continuous exposure to TWD over three generations exacerbated disease outcome in third generation offspring as compared to those fed TWD directly.