Masri, S, et al. Partitioning Circadian Transcription by Sirt6 Leads to Segregated Control of Cellular Metabolism. Cell, 2014. 158 (3):659-72.
Circadian rhythms and nutrient metabolism are intimately linked. NAD metabolism and the family of NAD-dependent deacetylases (SIRT1-7) have been shown to be involved in the nexus between circadian rhythms and metabolism. However, the precise molecular role of specific sirtuins was not known. Thus, investigators used metabolomics and transcriptomics to contrast the SIRT1 with SIRT6. Clear differential metabolic roles were revealed as SIRT6 was shown to have a major role in hepatic lipid metabolism, ultimately by controlling circadian chromatin recruitment of SREBP-1 – a master regulator of fatty acid and cholesterol metabolism. Given the major circadian control of metabolism, the dissection of key players like those shown here will be important in order to identify targets for potentially combating obesity-related diseases. This case in particular (identifying a key role in hepatic lipid metabolism for SIRT6) illustrates the importance of systems-wide analysis of circadian regulation
Metabolon results led to:
• A clear metabolic delineation of 2 members of the sirtuin family