SIRT6 is Essential for Adipocyte Differentiation through Regulating Mitotic Clonal Expansion. Mus musculus

Preadipocytes initiate differentiation into adipocytes through a cascade of events. Mitotic clonal expansion, as one of the earliest event, is essential for adipogenesis. However, the underlying mechanisms that regulate mitotic clonal expansion remain elusive. SIRT6 is a member of the evolutionarily conserved sirtuin family of NAD+ dependent protein deacetylases and plays roles in genomic stability, aging, glucose metabolism and inflammatory response. Here, we show that SIRT6 deficiency in preadipocytes blocked their adipogenesis. Analysis of gene expression during adipogenesis reveals that KIF5C, which belongs to kinesin family, is negatively regulated by SIRT6. Furthermore, we show that KIF5C is a negative factor for adipogenesis through interacting with CK2α’, a catalytic subunit of CK2. This interaction blocks CK2α’ nuclear translocation and CK2 kinase activity, and inhibits mitotic clonal expansion during adipogenesis. Thus, SIRT6 acts as an important factor of adipogenesis through inhibiting KIF5C expression and enhancing CK2 kinase activity. Overall design: Identification of genes expressed in WT vs. SIRT6 inhibitation under three time point (T=0, 20 40) conditions with three replications per group.