Language
English
Publication Date
1-9-2024
Journal
Research Square
DOI
10.21203/rs.3.rs-3835159/v1
PMID
38260478
PMCID
PMC10802732
PubMedCentral® Posted Date
1-9-2024
PubMedCentral® Full Text Version
Pre-Print
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 Aspa knockout mice stimulated the pentose phosphate pathway and pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in Aspa 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.
Published Open-Access
yes
Recommended Citation
Felix, Jessica B; Saha, Pradip K; de Groot, Evelyn; et al., "N-Acetylaspartate From Fat Cells Regulates Postprandial Body Temperature" (2024). Faculty, Staff and Students Publications. 8043.
https://digitalcommons.library.tmc.edu/baylor_docs/8043