Mitochondrial pyruvate carrier is required for optimal brown fat thermogenesis

Brown adipose tissue (BAT) is composed of thermogenic cells that convert chemical energy into heat to help maintain a constant body temperature and counteract metabolic disease. Metabolite profiling of BAT showed increased pyruvate levels with cold exposure. Using U13C-glucose labeling experiments, we found that activated brown adipocytes increased labeling of pyruvate and TCA cycle intermediates. Although glucose oxidation has been implicated as being essential for thermogenesis, its requirement for efficient thermogenesis has not been directly tested. We report that mitochondrial pyruvate uptake is essential for optimal thermogenesis. Isotopic labeling experiments using U13C-glucose showed that loss of MPC1 led to impaired labeling of TCA cycle intermediates. Loss of MPC1 in BAT increased 3-hydroxybutyrate levels in blood and BAT in response to the cold, suggesting a compensatory mechanism for impaired mitochondrial oxidation of cytosolic pyruvate in BAT. Collectively, these studies highlight that complete glucose oxidation is essential for optimal brown fat thermogenesis.