Files and links (1)
Published, Version of Record (VoR)CC BY-NC-ND V4.0, Open
Journal article
N-acetylaspartate pathway is nutrient responsive and coordinates lipid and energy metabolism in brown adipocytes
Biochimica et biophysica acta. Molecular cell research, v 1866(3), pp 337-348
31 Aug 2018
PMID: 30595160
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
Metrics
Details
- Title
- N-acetylaspartate pathway is nutrient responsive and coordinates lipid and energy metabolism in brown adipocytes
- Creators
- Katharina Huber - Institute of Biochemistry, Graz University of Technology, Graz, Austria; Department of Cancer Biology, University of Pennsylvania, Philadelphia, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA.Dina C. Hofer - Graz University of TechnologySophie Trefely - Department of Cancer Biology, University of Pennsylvania, Philadelphia, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA; AJ Drexel Autism Institute, Drexel University, Philadelphia, USA.Helmut J. Pelzmann - Graz University of TechnologyCorina Madreiter-Sokolowski - Medical University of GrazMadalina Duta-Mare - Medical University of GrazStefanie Schlager - Medical University of GrazGert Trausinger - Joanneum ResearchSarah Stryeck - Medical University of GrazWolfgang F. Graier - BioTechMed-GrazDagmar Kolb - Medical University of GrazChristoph Magnes - Joanneum ResearchNathaniel W. Snyder - Drexel UniversityAndreas Prokesch - BioTechMed-GrazDagmar Kratky - BioTechMed-GrazTobias Madl - BioTechMed-GrazKathryn E. Wellen - Department of Cancer Biology, University of Pennsylvania, Philadelphia, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA.Juliane G. Bogner-Strauss - Graz University of Technology
- Publication Details
- Biochimica et biophysica acta. Molecular cell research, v 1866(3), pp 337-348
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000456228200003
- Scopus ID
- 2-s2.0-85053153082
- Other Identifier
- 991019168079904721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology