Comprehensive molecular characterization of surgical vs. dietary weight loss: impact on mammary tumor burden
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Doerstling, Steven S. Comprehensive Molecular Characterization of Surgical Vs. Dietary Weight Loss: Impact On Mammary Tumor Burden. 2017. https://doi.org/10.17615/hv02-0069APA
Doerstling, S. (2017). Comprehensive molecular characterization of surgical vs. dietary weight loss: impact on mammary tumor burden. https://doi.org/10.17615/hv02-0069Chicago
Doerstling, Steven S. 2017. Comprehensive Molecular Characterization of Surgical Vs. Dietary Weight Loss: Impact On Mammary Tumor Burden. https://doi.org/10.17615/hv02-0069- Last Modified
- February 26, 2019
- Creator
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Doerstling, Steven S.
- Affiliation: Gillings School of Global Public Health, Department of Nutrition
- Abstract
- Background: Obesity is a widespread health concern and established risk factor for basal-like breast cancer. However, studies are conflicted on the benefits of weight loss relevant to breast cancer prevention. Recent studies suggest that certain methods of robust weight loss with long-term maintenance, such as bariatric surgery, might in fact be able to reverse obesity-associated breast cancer risk. Hypothesis: We hypothesize that weight loss by sleeve gastrectomy will generate sufficient metabolic normalization to reverse obesity-driven mammary tumor burden more effectively than weight loss by diet alone. Methods: Mice were fed a low-fat control (CON) or high-fat diet-induced obesity (DIO) regimen for 15 weeks to model chronic obesity. DIO mice were randomized to continue on a high-fat diet (Obese) or undergo weight loss by either sleeve gastrectomy (~70% excision of the stomach) in combination with switching to a low-fat diet or by switching to a low-fat diet alone, resulting in formerly obese (FOB)-Surg and FOB-Diet mice, respectively. Additionally, a subset of normal weight (NW) Control mice (Con, n=25) was maintained on a low-fat diet throughout the study. NW Control, FOB-Diet, and Obese mice underwent a sham procedure to control for the insult of surgery. FOB-Surg and FOB-Diet mice did not lose a significantly different amount of weight and body fat; both groups had significantly lower weight and percent body fat than Obese mice. Eight weeks after surgical procedures and diet switches, all mice on study were orthotopically injected with E0771 mammary tumor cells, which model BLBC. Results: At the end of study, ex vivo tumor volume in FOB-Surg mice was not significantly different from NW Control mice and significantly different from Obese mice. However, tumor volume in FOB-Diet mice was significantly different from NW Control mice and not significantly different from Obese mice. In addition, FOB-Surg mice had levels of serum tumor necrosis factor-alpha (TNF-a), insulin, and mammary adipocyte size that were not significantly different from NW Control mice and significantly different from FOB-Diet and Obese mice. Lastly, pathway analysis of mammary tissue gene expression revealed redundant upregulation of genes in extracellular matrix remodeling and growth factor signaling in Obese vs. FOB-Surg and FOB-Diet vs. FOB-Surg mice. Conclusions: Our results demonstrate that surgical weight loss imparted a plurality of metabolic advantages, functional genomic changes, and successful reversal of obesity-associated mammary tumor burden that were not similarly achieved by dietary weight loss.
- Date of publication
- spring 2017
- Keyword
- DOI
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- Rights statement
- In Copyright
- Note
- Funding: Summer Undergraduate Research Fellowship
- Funding: Dunlevie Honors Undergraduate Research Fund
- Advisor
- Hursting, Stephen
- Degree
- Bachelor of Science in Public Health
- Academic concentration
- Nutrition
- Honors level
- Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Graduation year
- 2017
- Language
- English
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