Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues.
Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues.
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天冬酰胺增强 mTORC1 信号传导，促进脂肪组织中的产热和糖酵解
DOI：
10.15252/embj.2021108069
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发表时间：
2021-12-15
期刊：
影响因子：
--
通讯作者：
Pan D
中科院分区：
文献类型：
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作者：
Xu Y;Shi T;Cui X;Yan L;Wang Q;Xu X;Zhao Q;Xu X;Tang QQ;Tang H;Pan D
棕色和米色脂肪专门用于通过将葡萄糖和脂肪酸氧化产生的能量作为热量耗散来消耗能量。虽然葡萄糖和脂肪酸代谢在生热脂肪组织中已被广泛研究，但氨基酸在调节适应性生热中的作用仍然很少研究。在这里，我们报告说，棕色和米色脂肪细胞中补充天冬酰胺显着上调生热转录程序和脂肪生成基因表达，从而使天冬酰胺喂养的小鼠表现出更好的耐冷性。在饮食引起的肥胖小鼠中，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，表现为体重增加减弱和糖耐量改善。代谢组学和 13C-葡萄糖通量分析表明，天冬酰胺补充剂可刺激糖酵解，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 mTORC1 通路，从而促进生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影响脂肪组织中的糖酵解和产热活性，为改善全身能量稳态提供了可能的营养策略。非必需氨基酸天冬酰胺通过 mTORC1-4E-BP1-糖酵解轴促进脂肪细胞能量耗散。
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. Adipocyte energy dissipation is fueled by the non‐essential amino acid asparagine via an mTORC1‐4E‐BP1‐glycolysis axis.