N-acetylaspartate from fat cells regulates postprandial body temperature

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

N-acetylaspartate (NAA), the brain's second most abundant metabolite, provides essential substrates for myelination through its hydrolysis 1 . 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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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