METABOENDOCRINE AND INFLAMMATORY CORRELATES OF TUMOR GROWTH IN

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METABOENDOCRINE AND INFLAMMATORY CORRELATES OF TUMOR GROWTH IN A MOUSE MODEL OF BREAST CANCER

METABOENDOCRINE AND INFLAMMATORY CORRELATES OF TUMOR GROWTH IN A MOUSE MODEL OF BREAST CANCER Tori Mc. Farlane | B. S. P. H. Nutrition Faculty Advisor: Stephen D. Hursting, MPH, Ph. D Graduate Mentor: Kristina Camp, DVM Department of Nutrition

My Research Question. . . How do dietary and surgical weight loss interventions differentially

My Research Question. . . How do dietary and surgical weight loss interventions differentially affect tumor growth in a mouse model of breast cancer? What changes in important metabolic and inflammatory markers are correlated with diminished tumor growth? Why This? Breast cancer is currently the second leading cause of cancer-related death, with an estimated 276, 480 invasive cases estimated to be diagnosed in American women this year [1]. Obesity, a well-established risk factor of breast cancer, burdens approximately 40% of U. S. adults [2], and often causes inflammation and metabolic dysregulation associated with increased breast cancer growth and progression [3]. Previous research in the Hursting lab has shown that both dietary and surgical interventions to promote weight loss also diminish tumor growth in a mouse model of breast cancer. This project sought to compare similar and different metaboendocrine and inflammatory markers that are potentially contributing to this beneficial outcome in obese mice receiving either calorie restriction (dietary intervention) or gastric bypass (surgical intervention). At the beginning of this study, diet-induced obese (DIO) mice were generated through high-fat diet feeding; after 15 weeks, mice received either sham or vertical sleeve gastrectomy (VSG) procedures. VSG mice were fed a low-fat diet post-operatively (VSG LF), while sham mice were assigned to either chronic or intermittent calorie restriction in order to induce weight loss (CCR and ICR, respectively). A group of sham mice were also maintained on a DIO diet as a control.

The Results A Calorie restriction (CCR and ICR groups) and gastric bypass (VSG LF)

The Results A Calorie restriction (CCR and ICR groups) and gastric bypass (VSG LF) both improved metabolic and inflammatory markers compared to mice that did not receive a weight loss intervention (DIO group). However, compared to gastric bypass, calorie restriction resulted in significantly decreased tumor mass (A) which was associated with decreased fasted blood glucose levels (B). Other metaboendocrine and inflammatory markers were similar between calorie restriction and gastric bypass groups. These findings suggest that glucose regulation may play an important role in reducing mammary tumor burden in mice. C E D F G B Leptin/Adiponectin Ratio Leptin and adiponectin are hormones secreted by fat tissue. The ratio of leptin to adiponectin serves as a biomarker for adipose tissue inflammation. Compared to the preintervention obese state, the ratio was significantly reduced in all three, dietary (CCR/ICR) and surgical (VSG LF), intervention groups. DIO: Diet-Induced Obese CCR: Chronic Calorie Restriction ICR: Intermittent Calorie Restriction VSG LF: Vertical Sleeve Gastrectomy Low-Fat Insulin is a hormone that regulates blood glucose levels. While we expected all weight loss interventions to decrease insulin levels compared to obese mice (DIO), no significant differences were observed. GLP-1 is a hormone produced in the small intestine. It promotes insulin secretion to ultimately lower blood glucose levels. Chronic caloric restriction (CCR) significantly increased GLP 1, but intermittent caloric restriction (ICR) did not increase GLP-1 to statistically significant levels. IL-6 Cytokines are small proteins that function as signaling molecules. IL-6 is a pro-inflammatory cytokine produced in response to tissue damage or infection. Compared to obese mice (DIO), chronic and intermittent caloric restriction (CCR and ICR) had reduced circulating IL-6 levels. TNF-α Tumor necrosis factor-α is another proinflammatory cytokine that may contribute to breast cancer progression. TNF-α was reduced in both calorie restriction (CCR and ICR) and gastric bypass (VSG LF) groups compared to obese mice (DIO). p < 0. 05