Abstract 797: Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation

Obesity is associated with increased incidence and worse prognosis of more than one dozen tumor types; however, the molecular mechanisms for this association are unknown. We hypothesized that insulin, which is elevated in obesity-driven insulin resistance, would increase tumor glucose oxidation in obesity-associated tumors. To test this hypothesis, we developed a stable isotope method in which tumor cells are incubated in physiological concentrations (5 mM) of [13C6] glucose and the ratio of pyruvate dehydrogenase flux to citrate synthase flux (VPDH/VCS, i.e. the percent of total mitochondrial oxidation fueled by glucose oxidation) is given as [4,5-13C2]glutamate/[13C3]alanine, measured by gas chromatography/mass spectrometry and liquid chromatography-tandem mass spectrometry respectively. Using this method, we found that both breast cancer (4T1) and colon cancer (MC38) cells, tumors that are associated with obesity, exhibit greater relative rates of glucose oxidation to total mitochondrial oxidation (VPDH/VCS 61±3% and 60±2%, respectively) than melanoma (YUMM) and Renca (renal cell carcinoma) cells (41±4% and 37±2%, respectively; P Citation Format: Aviva Rabin-Court, Gerald I. Shulman, Rachel J. Perry. Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 797.