The Impact of Obesity Reversal on Breast Cancer-Promoting Chronic INflammation: The Role of Diet Type and Gut Microbiota Public Deposited

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  • February 26, 2019
Creator
  • Shamsunder, Meghana
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Introduction: Obesity is growing epidemic and risk factor for the development of breast cancer. Studies conducted to date have not shown a consistent relationship between weight loss and the risk of cancer development however there has been an increasing focus on calorie restriction diets and intermittent energy restriction diets and their impact on breast cancer progression. We aimed to improve the understanding of how different energy restriction diets affect obesity-associated, tumor-promoting inflammation in breast cancer and the role of gut microbiota in this inflammation. Methods: Female C57BL/6 mice were randomized onto control diet (n = 20) and diet induced obesity diet (n = 80). At week 15, the diet induced obesity (DIO) group was randomized to four different groups: mice that remained on DIO diet, a high-carb calorie restriction diet, a low-carb calorie restriction diet, and an intermittent energy restriction diet. At week 25, mice were injected with a mixture of E0771 cells. Three to four weeks later, a final sacrifice was performed. Serum and tissue samples were collected and analyzed to determine significant differences in body composition, tumor weight and size, serum hormone and adipokine levels, and local mRNA expression of cytokines and proteins. Results: The obese group had significantly greater body weight, visceral white adipose tissue, and more severe tumor outcomes than the Control and the calorie restriction groups (High Carb Calorie Restriction, Low Carb Calorie Restriction, and Intermittent Energy Restriction). Additionally, the obese group had significant dysfunctional changes in serum hormones and adipokines and greater expression of pro-inflammatory cytokines than anti-inflammatory cytokine. The calorie restriction groups reversed this. Lastly, the obese group presented with a more permeable gut epithelium and lower expression of colonic occludin that maintains gut impermeability. This led to increased serum lipopolysaccharides in the obese group. There was little to no reversal of these changes in the calorie restriction groups. Conclusion: Obesity induced significant systemic and local changes in the mice that resulted in more severe tumors. The calorie restriction diets were able to reverse these changes (except for changes in the gut epithelium and serum lipopolysaccharide levels) and had less severe mammary tumors.
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  • In Copyright
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  • Funding: None
Advisor
  • Hursting, Stephen
Degree
  • Bachelor of Science in Public Health
Honors level
  • Highest Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Extent
  • 31
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