N-Acetylaspartate From Fat Cells Regulates Postprandial Body Temperature

Authors

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

Language

English

Publication Date

8-1-2025

Journal

Nature Metabolism

DOI

10.1038/s42255-025-01334-6

PMID

40702167

PMCID

PMC12373498

PubMedCentral® Posted Date

7-23-2025

PubMedCentral® Full Text Version

Post-print

Abstract

N-acetylaspartate (NAA), the brain’s second most abundant metabolite, provides essential substrates for myelination through its hydrolysis1. However, the physiological roles of NAA in other tissues remain unknown. Here, we show that aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs blood NAA levels for postprandial body temperature regulation. Genetic ablation of Aspa in mice resulted in systemically elevated NAA levels, and the ensuing accumulation in WAT stimulated pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in Aspa knockout cells. Additionally, serum NAA levels positively correlated with the abundance of the pyrimidine intermediate orotidine 5′-monophosphate, and this relationship predicted lower body mass index in humans. Using whole-body and tissue-specific knockout mouse models, we observed that fat cells provided plasma NAA and suppressed postprandial body temperature elevation. Moreover, unopposed NAA from adipocytes greatly enhanced whole-body glucose disposal exclusively in WAT. Exogenous NAA also increased plasma pyrimidines and lowered body temperature. These data place WAT-derived NAA as an endocrine regulator of postprandial body temperature and define broader roles for metabolic homeostasis.

Keywords

Animals, Mice, Aspartic Acid, Postprandial Period, Humans, Mice, Knockout, Male, Adipocytes, Adipose Tissue, White, Mice, Inbred C57BL, Body Temperature, Glucose, Body Temperature Regulation, Female, Pyrimidines, Fat metabolism, Homeostasis, Metabolism

Published Open-Access

yes

Recommended Citation

Felix, Jessica B; Saha, Pradip K; de Groot, Evelyn L; et al., "N-Acetylaspartate From Fat Cells Regulates Postprandial Body Temperature" (2025). Faculty and Staff Publications. 4367.
https://digitalcommons.library.tmc.edu/baylor_docs/4367