Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.

Détails

Ressource 1Télécharger: BIB_4C59E5F3E282.P001.pdf (1368.92 [Ko])
Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_4C59E5F3E282
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.
Périodique
Basic Research in Cardiology
Auteur(s)
Winnik S., Gaul D.S., Preitner F., Lohmann C., Weber J., Miranda M.X., Liu Y., van Tits L.J., Mateos J.M., Brokopp C.E., Auwerx J., Thorens B., Lüscher T.F., Matter C.M.
ISSN
1435-1803 (Electronic)
ISSN-L
0300-8428
Statut éditorial
Publié
Date de publication
2014
Volume
109
Numéro
1
Pages
399
Langue
anglais
Résumé
Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR(-/-)) and LDLR/Sirt3 double-knockout (Sirt3(-/-)LDLR(-/-)) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR(-/-) mice. Sirt3 deficiency does not affect atherosclerosis in LDLR(-/-) mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/01/2014 8:40
Dernière modification de la notice
20/08/2019 14:00
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