The phosphorylation status of T522 modulates tissue-specific functions of SIRT1 in energy metabolism in mice.

ABSTRACT: SIRT1, the most conserved mammalian NAD⁺-dependent protein deacetylase, is an important metabolic regulator. However, the mechanisms by which SIRT1 is regulated in vivo remain unclear. Here, we report that phosphorylation modification of T522 on SIRT1 is crucial for tissue-specific regulation of SIRT1 activity in mice. Dephosphorylation of T522 is critical for repression of its activity during adipogenesis. The phospho-T522 level is reduced during adipogenesis. Knocking-in a constitutive T522 phosphorylation mimic activates the β-catenin/GATA3 pathway, repressing PPARγ signaling, impairing differentiation of white adipocytes, and ameliorating high-fat diet-induced dyslipidemia in mice. In contrast, phosphorylation of T522 is crucial for activation of hepatic SIRT1 in resp

SUBMITTER: Lu J 

PROVIDER: S-EPMC5412809 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature