| Autor: |
Hofer DC; Institute of Biochemistry, Graz University of Technology, Graz, Austria.; Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Zirkovits G; Institute of Biochemistry, Graz University of Technology, Graz, Austria., Pelzmann HJ; Institute of Biochemistry, Graz University of Technology, Graz, Austria.; Fresenius Kabi Austria GmbH, Graz, Austria., Huber K; Institute of Biochemistry, Graz University of Technology, Graz, Austria.; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland., Pessentheiner AR; Institute of Biochemistry, Graz University of Technology, Graz, Austria.; Department of Medicine, University of California-San Diego, La Jolla, California, USA., Xia W; Institute of Biochemistry, Graz University of Technology, Graz, Austria., Uno K; Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan., Miyazaki T; Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan., Kon K; Department of Clinical Pharmacology, University of Toyama, Toyama, Japan., Tsuneki H; Department of Clinical Pharmacology, University of Toyama, Toyama, Japan., Pendl T; Institute of Molecular Biosciences, NAWI Graz, Graz, Austria., Zoughbi WA; Institute of Pathology, Medical University of Graz, Graz, Austria., Madreiter-Sokolowski CT; Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria., Trausinger G; Joanneum Research, HEALTH-Institute for Biomedicine and Health Sciences, Graz, Austria., Abdellatif M; Department of Cardiology, Medical University of Graz, Graz, Austria., Schoiswohl G; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Schreiber R; Institute of Molecular Biosciences, University of Graz, Graz, Austria., Eisenberg T; Institute of Molecular Biosciences, NAWI Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Magnes C; Joanneum Research, HEALTH-Institute for Biomedicine and Health Sciences, Graz, Austria., Sedej S; Department of Cardiology, Medical University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Eckhardt M; Institute of Biochemistry and Molecular Biology, University of Bonn, Bonn, Germany., Sasahara M; Department of Pathology, University of Toyama, Toyama, Japan., Sasaoka T; Department of Clinical Pharmacology, University of Toyama, Toyama, Japan., Nitta A; Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan., Hoefler G; Institute of Pathology, Medical University of Graz, Graz, Austria., Graier WF; Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Kratky D; Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.; BioTechMed-Graz, Graz, Austria., Auwerx J; Laboratory of Integrative and Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Bogner-Strauss JG; Institute of Biochemistry, Graz University of Technology, Graz, Austria.; BioTechMed-Graz, Graz, Austria. |
| Abstrakt: |
N -acetylaspartate (NAA) is synthesized by aspartate N -acetyltransferase (gene: Nat8l ) from acetyl-coenzyme A and aspartate. In the brain, NAA is considered an important energy metabolite for lipid synthesis. However, the role of NAA in peripheral tissues remained elusive. Therefore, we characterized the metabolic phenotype of knockout (ko) and adipose tissue-specific (ako) Nat8l -ko mice as well as NAA-supplemented mice on various diets. We identified an important role of NAA availability in the brain during adolescence, as 75% of Nat8l -ko mice died on fat-free diet (FFD) after weaning but could be rescued by NAA supplementation. In adult life, NAA deficiency promotes a beneficial metabolic phenotype, as Nat8l -ko and Nat8l -ako mice showed reduced body weight, increased energy expenditure, and improved glucose tolerance on chow, high-fat, and FFDs. Furthermore, Nat8l -deficient adipocytes exhibited increased mitochondrial respiration, ATP synthesis, and an induction of browning. Conversely, NAA-treated wild-type mice showed reduced adipocyte respiration and lipolysis and increased de novo lipogenesis, culminating in reduced energy expenditure, glucose tolerance, and insulin sensitivity. Mechanistically, our data point to a possible role of NAA as modulator of pancreatic insulin secretion and suggest NAA as a critical energy metabolite for adipocyte and whole-body energy homeostasis.-Hofer, D. C., Zirkovits, G., Pelzmann, H. J., Huber, K., Pessentheiner, A. R., Xia, W., Uno, K., Miyazaki, T., Kon, K., Tsuneki, H., Pendl, T., Al Zoughbi, W., Madreiter-Sokolowski, C. T., Trausinger, G., Abdellatif, M., Schoiswohl, G., Schreiber, R., Eisenberg, T., Magnes, C., Sedej, S., Eckhardt, M., Sasahara, M., Sasaoka, T., Nitta, A., Hoefler, G., Graier, W. F., Kratky, D., Auwerx, J., Bogner-Strauss, J. G. N -acetylaspartate availability is essential for juvenile survival on fat-free diet and determines metabolic health. |
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