Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues.

Abstract

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 13 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.

• Authors: Yingjiang Xu, Ting Shi, Xuan Cui, Linyu Yan, Qi Wang, Xiaoyan Xu, Qingwen Zhao, Xiaoxuan Xu, Qi-Qun Tang, Huiru Tang, Dongning Pan
• Journal: The EMBO journal (EMBO J) Vol. 40 Issue 24 Pg. e108069 (12 15 2021) ISSN: 1460-2075 [Electronic] England
• PMID: 34704268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Chemical References

• Asparagine
• Mechanistic Target of Rapamycin Complex 1

Topics

• Animals
• Asparagine (pharmacology)
• Cells, Cultured
• Cold Temperature
• Gene Expression Regulation (drug effects)
• Glycolysis (drug effects)
• Male
• Mechanistic Target of Rapamycin Complex 1 (genetics)
• Metabolomics
• Mice
• Signal Transduction (drug effects)
• Thermogenesis (drug effects)