ArticleBiochimica et biophysica acta. Molecular cell research2019
N-acetylaspartate pathway is nutrient responsive and coordinates lipid and energy metabolism in brown adipocytes.
Article in Biochimica et biophysica acta. Molecular cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- N-Acetylaspartate Synthesis as a Thermodynamic Relief Mechanism for Mitochondrial Aspartate Aminotransferase.bioRxiv : the preprint server for biology · 2026Article
- The Emerging Role of N-Acetylaspartate in Cancer.International journal of molecular sciences · 2026Review
- Identification and Transcriptomic Analysis of Mitochondria-Related Gene Signatures in Obesity.Metabolites · 2026Article
- Much ado about NAA-thing.Nature metabolism · 2025Article
- New insights into metabolism dysregulation after TBI.Journal of neuroinflammation · 2024Review
- Quantification of N-acetyl-l-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease.Molecular genetics and metabolism · 2024Article
- Acetylcarnitine shuttling links mitochondrial metabolism to histone acetylation and lipogenesis.Science advances · 2023Article
- Acetyl-CoA metabolism in cancer.Nature reviews. Cancer · 2023Review
- LncRNA GAS5 promotes spermidine‑induced autophagy through the miRNA‑31‑5p/NAT8L axis in pulmonary artery endothelial cells of patients with CTEPH.Molecular medicine reports · 2022Article
- The pathogenesis of, and pharmacological treatment for, Canavan disease.Drug discovery today · 2022Review
- N-Acetyl Transferase, Shati/Nat8l, in the Dorsal Hippocampus Suppresses Aging-induced Impairment of Cognitive Function in Mice.Neurochemical research · 2022Article
- The PROVIT Study-Effects of Multispecies Probiotic Add-on Treatment on Metabolomics in Major Depressive Disorder-A Randomized, Placebo-Controlled Trial.Metabolites · 2022Article
- PAT2 regulates vATPase assembly and lysosomal acidification in brown adipocytes.Molecular metabolism · 2022Article
- Article
- p53 Regulates a miRNA-Fructose Transporter Axis in Brown Adipose Tissue Under Fasting.Frontiers in genetics · 2022Article
- Regulation of amino acid metabolism inFrontiers in nutrition · 2022Article
- Nicotinamide Adenine Dinucleotide Biosynthetic Impairment and Urinary Metabolomic Alterations Observed in Hospitalized Adults With COVID-19-Related Acute Kidney Injury.Kidney international reports · 2021Article
- Article
- In vivo isotope tracing reveals the versatility of glucose as a brown adipose tissue substrate.Cell reports · 2021Article
- Harnessing Ionic Selectivity in Acetyltransferase Chemoproteomic Probes.ACS chemical biology · 2021Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
The discovery of significant amounts of metabolically active brown adipose tissue (BAT) in adult humans renders it a promising target for anti-obesity therapies by inducing weight loss through increased energy expenditure. The components of the N-acetylaspartate (NAA) pathway are highly abundant in BAT. Aspartate N-acetyltransferase (Asp-NAT, encoded by Nat8l) synthesizes NAA from acetyl-CoA and aspartate and increases energy expenditure in brown adipocytes. However, the exact mechanism how the NAA pathway contributes to accelerated mobilization and oxidation of lipids and the physiological regulation of the NAA pathway remained elusive. Here, we demonstrate that the expression of NAA pathway genes corresponds to nutrient availability and specifically responds to changes in exogenous glucose. NAA is preferentially produced from glucose-derived acetyl-CoA and aspartate and its concentration increases during adipogenesis. Overexpression of Nat8l drains glucose-derived acetyl-CoA into the NAA pool at the expense of cellular lipids and certain amino acids. Mechanistically, we elucidated that a combined activation of neutral and lysosomal (acid) lipolysis is responsible for the increased lipid degradation. Specifically, translocation of the transcription factor EB to the nucleus activates the biosynthesis of autophagosomes and lysosomes. Lipid degradation within lysosomes accompanied by adipose triglyceride lipase-mediated lipolysis delivers fatty acids for the support of elevated mitochondrial respiration. Together, our data suggest a crucial role of the NAA pathway in energy metabolism and metabolic adaptation in BAT.
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Registered trials
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