Abstract 1811: Social isolation stress-induced obesity increases mammary cancer risk

Abstract

Abstract Objectives: In this study, we are investigating whether social isolation stress and an obesity-inducing diet (OID), alone or in combination, increase neuropeptide Y (NPY) levels and mammary cancer risk, and induce central obesity and insulin resistance in female C57BL/6 mice. Methods: We first either group-housed or stressed by social isolation mice starting at six weeks of age (WOA) for two weeks and then sacrificed them to obtain mammary glands and blood for NPY assay. A larger group of female mice were then either socially-isolated or group-housed from the age of 21 days, and we began feeding them control AIN93G based diet containing 2% lard or an obesity-inducing AIN93G based diet containing 30% lard. The mice were given a single subcutaneous dose of 15 mg/kg medroxyprogesterone acetate (MPA) at 6 WOA and weekly administrations of 1 mg of 7,12-dimethylbenz[a]anthracene (DMBA) from 7 to 10 WOA by gavage to induce mammary tumors. Tumorigenicity and body weight were followed until 28 WOA. Insulin tolerance testing was performed at three months of age. Tissue and blood samples were harvested at the end of tumor monitoring period. Results: Mammary glands of the 2 week-long isolated mice contained significantly more (p = 0.0399, t-test) terminal end buds (TEBs) than the glands of control mice. NPY levels in blood, measured by peptide enzyme immunoassay (EIA) (Peninsula Laboratories), were significantly higher in the socially-isolated mice were (p = 0.0475, t-test) than the group-housed control mice. Mice that were socially-isolated and fed an OID gained the most weight, and the socially-isolated, control diet fed mice gained more weight than the group-housed, control diet fed mice (week 5 of isolation stress p<0.001; OID: p=0.002).The socially-isolated, OID fed mice were found to be insulin resistant. These mice had significantly higher glucose levels at 60 minutes after insulin injection then the three other groups (p=0.009). We also found that there was a significant difference in mammary tumor incidence induced by a carcinogen over time in the socially-isolated, OID fed mice versus the group-housed control diet mice (log-rank survival, p = 0.0288). Additionally, a difference was seen between the isolated control-fed and OID-fed mice (p = 0.0629). This is indicative that there could be an additive effect between obesity and isolation. Conclusions: Our data acquired from these socially isolated and obese mice support the growing body of literature that social isolation and a high fat diet not only induces obesity and insulin resistance in mice, but also, through these changes, increases the risk of mammary cancer. An increase in NPY levels may be responsible for the increase in body weight and insulin resistance, and elevated mammary cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1811. doi:10.1158/1538-7445.AM2011-1811