Combined fatty acid esterification and lipolysis, termed lipid cycling, is an ATP‐consuming process that contributes to energy expenditure. Therefore, interventions that stimulate energy expenditure through lipid cycling are of great interest. Here we find that pharmacological and genetic inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes activates lipid cycling and energy expenditure, even in the absence of adrenergic stimulation. We show that the resulting increase in ATP demand elevates mitochondrial respiration coupled to ATP synthesis and fueled by lipid oxidation. We identify that glutamine consumption and the Malate‐Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). We thus demonstrate that energy expenditure through enhanced lipid cycling can be activated in brown adipocytes by decreasing mitochondrial pyruvate availability. We present a new mechanism to increase energy expenditure and fat oxidation in brown adipocytes, which does not require adrenergic stimulation of mitochondrial uncoupling.

中文翻译：

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阻断棕色脂肪细胞中线粒体丙酮酸的输入通过脂质循环诱导能量浪费

脂肪酸酯化和脂肪分解的结合，称为脂质循环，是一个消耗 ATP 的过程，有助于能量消耗。因此，通过脂质循环刺激能量消耗的干预措施引起了人们的极大兴趣。在这里，我们发现棕色脂肪细胞中线粒体丙酮酸载体 (MPC) 的药理学和遗传抑制激活了脂质循环和能量消耗，即使在没有肾上腺素能刺激的情况下也是如此。我们表明，由此导致的 ATP 需求增加提高了线粒体呼吸与 ATP 合成的耦合，并由脂质氧化推动。我们发现谷氨酰胺消耗和苹果酸-天冬氨酸穿梭是棕色脂肪细胞 (MASHEEBA) 中 MPC 抑制诱导的能量消耗增加所必需的。因此，我们证明通过增强脂质循环的能量消耗可以通过降低线粒体丙酮酸的可用性在棕色脂肪细胞中被激活。我们提出了一种增加棕色脂肪细胞能量消耗和脂肪氧化的新机制，这不需要肾上腺素能刺激线粒体解偶联。