Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences, Fudan University, Shanghai, China.
State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Metabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular Phenomics, Zhongshan Hospital, Fudan University, Shanghai, China.
EMBO J. 2021 Dec 15;40(24):e108069. doi: 10.15252/embj.2021108069. Epub 2021 Oct 27.
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 C-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.
棕色脂肪和米色脂肪通过将葡萄糖和脂肪酸氧化产生的能量以热量的形式消耗,从而专门用于能量消耗。虽然在产热脂肪组织中已经广泛研究了葡萄糖和脂肪酸代谢,但氨基酸在调节适应性产热中的作用仍研究甚少。在这里,我们报告说,在棕色和米色脂肪细胞中补充天冬酰胺会极大地上调产热转录程序和脂肪生成基因的表达,以至于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敏感,表现为体重增加减缓和葡萄糖耐量改善。代谢组学和 C-葡萄糖通量分析显示,天冬酰胺补充刺激糖酵解为脂肪细胞的产热和脂肪生成提供燃料。在机制上,天冬酰胺刺激 mTORC1 途径,促进产热基因和糖酵解关键酶的表达。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性,为改善全身能量平衡提供了一种可能的营养策略。