Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Jian Fang, Alessandro Ianni, Christian Smolka, Olesya Vakhrusheva, Hendrik Nolte, Marcus Krüger, Astrid Wietelmann, Nicolas G. Simonet, Juan M. Adrian-Segarra, Alejandro Vaquero, Thomas Braun, Eva Bober

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Sirtuins (Sirt1–Sirt7) are NAD+-dependent protein deacetylases/ ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16. Sirt7 restricts Sirt1 activity by preventing Sirt1 autodeacetylation causing enhanced Sirt1 activity in Sirt7−/− mice. Increased Sirt1 activity in Sirt7−/− mice blocks PPARγ and adipocyte differentiation, thereby diminishing accumulation of white fat. Thus, reduction of Sirt1 activity restores adipogenesis in Sirt7−/− adipocytes in vitro and in vivo. We disclosed a principle controlling Sirt1 activity and uncovered an unexpected complexity in the crosstalk between two different sirtuins. We propose that antagonistic interactions between Sirt1 and Sirt7 are pivotal in controlling the signaling network required for maintenance of adipose tissue.

Original languageEnglish
Pages (from-to)E8352-E8361
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number40
DOIs
StatePublished - 3 Oct 2017
Externally publishedYes

Keywords

  • Acetylation
  • Adipogenesis
  • Sirtuin

Fingerprint

Dive into the research topics of 'Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1'. Together they form a unique fingerprint.

Cite this