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N-acetylaspartate from fat cells regulates postprandial body temperature
Jessica B Felix1,2,3, Pradip K Saha1,2, Evelyn L de Groot1,2,4
1Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX, USA.
Nature Metabolism
|July 23, 2025
Summary
White adipose tissue (WAT) expresses aspartoacylase (ASPA), controlling blood N-acetylaspartate (NAA) levels. WAT-derived NAA regulates body temperature and glucose disposal, revealing new roles for this metabolite in metabolic homeostasis.
Area of Science:
- Metabolic biochemistry
- Endocrinology
- Neuroscience
Background:
- N-acetylaspartate (NAA) is abundant in the brain, crucial for myelination.
- Physiological roles of NAA outside the central nervous system are largely unknown.
- Aspartoacylase (ASPA) is the enzyme responsible for NAA hydrolysis.
Purpose of the Study:
- To investigate the role of aspartoacylase (ASPA) in white adipose tissue (WAT).
- To determine the function of NAA in non-neural tissues, particularly in relation to body temperature regulation and metabolism.
Main Methods:
- Genetic manipulation using whole-body and tissue-specific Aspa knockout mouse models.
- Stable isotope tracing to track glucose metabolism and pyrimidine production.
- Measurement of serum NAA levels and correlation with metabolic parameters.
Main Results:
- Aspa ablation in mice led to elevated systemic NAA levels and increased pyrimidine production in WAT.
- WAT-derived NAA suppresses postprandial body temperature elevation and enhances glucose disposal.
- Serum NAA levels correlated with pyrimidine intermediates and predicted lower BMI in humans.
Conclusions:
- WAT-derived NAA acts as an endocrine regulator of postprandial body temperature.
- NAA plays broader roles in metabolic homeostasis beyond its known function in the brain.
- ASPA expression in WAT is critical for managing NAA levels and influencing energy balance.
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