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© 2020 The Obesity Society. Objective: The objectives of this study were to assess the role of mitochondrial pyruvate carriers (MPCs) in adipocyte development in vitro and determine whether MPCs are regulated in vivo by high-fat feeding in male and female C57BL/6J mice. Methods: This study utilized small interfering RNA-mediated knockdown to assess the requirement of MPC1 for adipogenesis in the 3T3-L1 model system. Treatment with UK-5099, a potent pharmacological MPC inhibitor, was also used to assess the loss of MPC activity. Western blot analysis was performed on adipose tissue samples from mice on a low-fat diet or a high-fat diet (HFD) for 12 weeks. Results: The loss of MPC expression via small interfering RNA-mediated knockdown or pharmacological inhibition did not affect adipogenesis of 3T3-L1 cells. In vivo studies indicated that expression of MPCs was significantly decreased in brown adipose tissue of male mice, but not female, on an HFD. Conclusions: Although MPCs are essential for pyruvate transport, MPCs are not required for adipogenesis in vitro, suggesting that other substrates can be used for energy production when the MPC complex is not functional. Also, a significant decrease in MPC1 and 2 expression occurred in brown fat, but not white fat, of male mice fed an HFD.

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