Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine-fed mice showed better cold tolerance. In mice with diet-induced obesity, the asparagine-fed group was more responsive to β3-adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and ¹³C-glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis.

中文翻译：

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天冬酰胺增强 mTORC1 信号以促进脂肪组织中的产热和糖酵解

棕色和米色脂肪专门用于能量消耗，通过将葡萄糖和脂肪酸氧化产生的能量作为热量消散。虽然已经在产热脂肪组织中广泛研究了葡萄糖和脂肪酸代谢，但对氨基酸参与调节适应性产热的研究仍然很少。在这里，我们报告在棕色和米色脂肪细胞中补充天冬酰胺显着上调产热转录程序和脂肪生成基因表达，因此天冬酰胺喂养的小鼠表现出更好的耐寒性。在饮食诱导肥胖的小鼠中，天冬酰胺喂养组对 β3-肾上腺素能受体激动剂的反应更灵敏，表现为体重增加缓慢和葡萄糖耐量改善。代谢组学和¹³C-葡萄糖通量分析显示，天冬酰胺补充剂会刺激糖酵解以促进脂肪细胞的产热和脂肪生成。从机制上讲，天冬酰胺刺激了 mTORC1 通路，促进了产热基因和糖酵解中关键酶的表达。这些发现表明，天冬酰胺的生物利用度会影响脂肪组织中的糖酵解和产热活动，为改善全身能量稳态提供了一种可能的营养策略。