Mammary Tumors Increase Diet-Induced Obesity And Insulin Resistance In Female Mmtv-Pymt Mice

Diabetes and cancer share multiple risk factors including obesity and insulin resistance, but the potential relationship between these two major diseases is unknown. Here we examined the metabolic effects of high-fat diet (HFD) feeding in female MMTV-PyMT mice, a breast cancer model expressing the polyoma middle T antigen driven by the Mouse Mammary Tumor Virus promoter. Female PyMT and wild type (WT) mice were fed a HFD (55% fat by calories) for 4 weeks starting at 4∼5 weeks of age (n=10-12/group). During HFD, PyMT mice became more obese than WT mice with significant increases in both fat and lean mass (Figure 1; *P<0.05). This was largely due to ∼5% and 30% decreases in energy expenditure and physical activity, respectively, in HFD-PyMT mice (Figure 2). Food intake did not differ between groups. Hyperinsulinemic-euglycemic clamps were performed to measure glucose metabolism in awake mice. HFD-PyMT mice showed increased insulin resistance with ∼25% decreases in glucose infusion rate and whole body glucose turnover compared to HFD-WT mice (Figure 3). Increased insulin resistance was due to significantly reduced glucose uptake in white adipose tissue (Figure 4). In conclusion, these results demonstrate that tumor-bearing female PyMT mice developed increased obesity and insulin resistance after high-fat feeding, and our findings implicate an important relationship between obesity, cancer, and type 2 diabetes. Disclosure H. Noh: None. H. Kang: None. J. Mercado-Matos: None. R.H. Friedline: None. S. Suk: None. X. Hu: None. D.A. Tran: None. L.A. Tauer: None. M. Ko: None. J. Choi: None. T. Luong: None. Y. Tsuchida: None. L.M. Shaw: None. J.K. Kim: None. Funding National Institutes of Health (5U2C-DK093000)