Figure 9.

NAD⁺-SIRT1 signaling fine-tunes the activity of key transcription factor networks to promote adipocyte function. (a) Schematic summary of the data obtained by combining quantitative proteomics and gene-expression analysis in adipocytes. Positive or negative effect of SIRT1 on the expression levels of individual molecules (top) or transcription factor pathways (bottom) is indicated by ‘+’ or ‘−’ sign, respectively. Molecules highlighted in red represent those whose interaction with SIRT1 to our knowledge has not been previously reported in the context of adipogenesis, adipose tissue function, or obesity. Evidence of an interaction between SIRT1 and molecules highlighted in green can be found in the literature. (b) Schematic summary of the effects of supplementation with NMN on gene-expression in ShScrambled and ShSIRT1 (pre)adipocytes. Positive or negative effect of NMN supplementation on the expression of indicated genes is indicated by ‘+’ or ‘−’ sign, respectively. Genes highlighted in red represent those whose SIRT1-dependence in response to NMN has not been previously reported, while those in green represent molecules whose association with NAD⁺-SIRT1 signaling is known. Molecules highlighted in blue represent those whose expression was altered by NMN in SIRT1-depleted (pre)adipocytes, which may reflect residual SIRT1 function or involvement of other NAD⁺-dependent proteins. Chemical structures of NMN and NAD⁺ are shown, and conversion of NMN to NAD⁺ occurs intracellularly by the action of NMNAT enzymes. The numbers indicate citations that link each molecule or pathway to the relevant section in “Discussion”.