N-acetylaspartate availability is essential for juvenile survival on fat-free diet and determines metabolic health.

Détails

ID Serval
serval:BIB_B794E4C617D5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
N-acetylaspartate availability is essential for juvenile survival on fat-free diet and determines metabolic health.
Périodique
FASEB journal
Auteur(s)
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.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
12/2019
Peer-reviewed
Oui
Volume
33
Numéro
12
Pages
13808-13824
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
Acetyl Coenzyme A/metabolism, Acetyltransferases/metabolism, Adipocytes/metabolism, Animals, Aspartic Acid/analogs & derivatives, Aspartic Acid/metabolism, Brain/metabolism, Diet, Fat-Restricted, Energy Metabolism/physiology, Insulin Resistance/physiology, Lipolysis/physiology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria/metabolism, NAA, acetyl-CoA, adipose tissue, energy homeostasis, insulin secretion
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/10/2019 15:15
Dernière modification de la notice
15/07/2020 5:26
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