Anthony Mancuso1,
Regina M. Young2, Brian D. Keith3, Craig B. Thompson4,
M. Celeste Simon2
1Cancer
Biology/Radiology, University of Pennsylviania, Philadelphia, PA, United
States; 2Cell and Developmental Biology, University of
Pennsylvania, Philadelphia, PA, United States; 3Cell and Molecular
Biology, University of Pennsylvania, Philadelphia, PA, United States; 4Sloan
Kettering Institute, New York, NY, United States
The effects of hypoxia on de novo lipogenesis in TSC2-/- mouse fibroblasts were examined with uniformly labeled 13C glucose and glutamine. These cells are a model for cancers with oncogenes that dis-regulate the akt/mTOR signaling cascade. The results demonstrate that both glucose and glutamine are important for de novo lipogenesis of both saturated and unsaturated fat under normoxic conditions. Hypoxia caused a marked reduction for both saturated and unsaturated lipid synthesis from glucose but not glutamine. The results have important implications for the design of anti-cancer therapies that target lipogenesis, for tumors with significant levels of hypoxia.