SIRT1 and metabolic dysfunction-associated steatohepatitis: The CLOCK-BMAL1 circadian transcription factors regulate hundreds of genes including the PPARs; hence, metabolic genes regulated by PPARs are rhythmically expressed.46 Mice lacking the expression of Clock are hyperphagic, obese, and develop NASH.47 The deacetylase SIRT1 forms a chromatin complex with CLOCK-BMAL1 and its activity is regulated in a circadian manner.