Sirt3 regulates adipogenesis and adipokine secretion via its enzymatic activity

The purpose of this research was to identify if Sirt3 plays a role in marrow adipogenesis and adipokines secretion, especially adiponectin using bone marrow‐derived stroma (ST2) cell model. Sirt3 overexpression leads to a significant increase in adipogenesis compared to controls. The induction of adipogenesis by Sirt3 is associated with increased gene expression of adipocyte markers as well as adiponectin/adipokines. In sharp contrast, the inhibition of Sirt3 exhibited significantly decreased adipogenesis, adipocyte markers, and adiponectin/adipokines compared to the controls. Interestingly, perilipin 1 (Plin 1) expression was decreased in Sirt3 induction but increased in Sirt3 inhibition. One hundred and fifteen mitochondrial acetylated peptides from 67 mitochondrial proteins had lower levels of acetylation in adipocytes induced by Sirt3 overexpression (Sirt3OE) compared to the control. Of the 67 proteins less enriched in acetylation, 22 acetylated proteins were decreased by more than twofold. These proteins are considered potential Sirt3 substrates in adipogenesis. In conclusion, Sirt3 has a novel, important role in modulating adipogenesis and adiponectin/adipokine expression. The connection axis among Sirt3‐adipogenesis‐adipokines was linked to its substrates by mass spectrometry analysis. These findings contribute to the efforts of revealing Sirt3 functions and Sirt3 usage as a potential target for treatment of metabolic homeostasis and diseases including type 2 diabetes.