来自脂肪细胞的N-乙酰天门冬氨酸调节餐后体温。

N-acetylaspartate from fat cells regulates postprandial body temperature.

作者信息

Felix Jessica B, Saha Pradip K, de Groot Evelyn, Tan Lin, Sharp Robert, Anaya Elizabeth S, Li Yafang, Quang Holly, Saidi Nooshin, Abushamat Layla, Ballantyne Christie M, Amos Christopher I, Lorenzi Philip L, Klein Samuel, Gao Xia, Hartig Sean M

机构信息

Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, TX.

Department of Medicine, Baylor College of Medicine, Houston, TX.

出版信息

Res Sq. 2024 Jan 9:rs.3.rs-3835159. doi: 10.21203/rs.3.rs-3835159/v1.

DOI:10.21203/rs.3.rs-3835159/v1

PMID:38260478

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10802732/

Abstract

N-acetylaspartate (NAA), the brain's second most abundant metabolite, provides essential substrates for myelination through its hydrolysis. However, activities and physiological roles of NAA in other tissues remain unknown. Here, we show aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs systemic NAA levels for postprandial body temperature regulation. Proteomics and mass spectrometry revealed NAA accumulation in WAT of knockout mice stimulated the pentose phosphate pathway and pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in knockout cells. Additionally, serum NAA positively correlates with the pyrimidine intermediate orotidine and this relationship predicted lower body mass index in humans. Using whole-body and tissue-specific knockout mouse models, we demonstrate that fat cells provided plasma NAA and suppressed postprandial body temperature elevation. Furthermore, exogenous NAA supplementation reduced body temperature. Our study unveils WAT-derived NAA as an endocrine regulator of postprandial body temperature and physiological homeostasis.

摘要

N-乙酰天门冬氨酸（NAA）是大脑中含量第二丰富的代谢物，通过水解为髓鞘形成提供必需的底物。然而，NAA在其他组织中的活性和生理作用仍不清楚。在这里，我们表明白色脂肪组织（WAT）中天冬氨酸酰基转移酶（ASPA）的表达控制着餐后体温调节的全身NAA水平。蛋白质组学和质谱分析显示，敲除小鼠的白色脂肪组织中NAA的积累刺激了磷酸戊糖途径和嘧啶的产生。稳定同位素示踪证实，敲除细胞中葡萄糖衍生的碳更多地掺入嘧啶代谢物中。此外，血清NAA与嘧啶中间体乳清苷呈正相关，这种关系预示着人类较低的体重指数。使用全身和组织特异性敲除小鼠模型，我们证明脂肪细胞提供血浆NAA并抑制餐后体温升高。此外，外源性补充NAA可降低体温。我们的研究揭示了白色脂肪组织衍生的NAA是餐后体温和生理稳态的内分泌调节因子。