Metaboendocrine And Inflammatory Correlates Of Tumor Growth Following Caloric Restriction And Vertical Sleeve Gastrectomy In A Mouse Model Of Breast Cancer.

Abstract Breast cancer is the second leading cause of cancer-related deaths in women living in the United States, and obesity is a well-established breast cancer risk and progression factor. Identifying interventions that effectively break the obesity-cancer link is therefore of great importance. This preclinical project aims to compare circulating cytokine and metaboendocrine hormone levels in formerly obese mice following dietary and surgical weight loss to identify serum markers potentially contributing to differential tumor mass outcomes. 20 control female C57BL/6 mice were maintained on a 10 kcal% fat diet throughout the study. All other mice were placed on a 60 kcal% diet for 15 weeks to promote diet-induced obesity (DIO), then randomized to receive either: a) vertical sleeve gastrectomy (VSG) with concurrent switch to control diet (16 mice); b) sham surgery and continuation of DIO regimen (18 mice); c) sham surgery with switch to a chronic calorie restricted (CCR; 30% daily calorie reduction) regimen (16 mice); or d) sham surgery with switch to an intermittent calorie restricted (ICR; 14% calorie reduction 5 days per week, 70% calorie reduction 2 non-consecutive days per week) regimen (19 mice). Following 10 weeks of weight loss interventions, serum from fasted animals was collected, and glucose (by glucometer), cytokines (by BioRad Mouse Cytokine 23-plex panel on a BioRad MAGPIX Instrument), and hormones (BioRad Mouse Diabetes 8-plex panel) were analyzed to characterize the systemic metaboendocrine and inflammatory environment immediately prior to orthotopic transplantation of E0771 mammary cancer cells. Surgical or dietary weight loss reduced serum cytokines that are classically induced by obesity, including interleukin 6 (IL-6), interleukin 2 (IL-2), and tumor necrosis factor alpha (TNFα), compared with DIO mice. Compared with VSG mice, only circulating chemokine ligand 13 (CXCL13) was significantly lower in serum from both CCR and ICR mice. Moreover, CCR and ICR mice displayed significantly lower fasting blood glucose levels and circulating plasminogen activator inhibitor-1 (PAI-1) compared with VSG mice. Therefore, these data suggest that decreased circulating CXCL13, PAI-1 and/or decreased fasted blood glucose may contribute to the superior antitumor effects of CCR and ICR versus VSG. This research was supported by R35CA197627 to S. Hursting. Citation Format: Tori L. McFarlane, Kristina Kalevas Camp, Elaine M. Glenny, Erika Rezeli, Michael F. Coleman, Stephen D. Hursting. Metaboendocrine and inflammatory correlates of tumor growth following caloric restriction and vertical sleeve gastrectomy in a mouse model of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2577.