Hormonal
Activation of SIRT1 (via fasting or chemical activators like SRT1720/SRT2183) directly deacetylates SREBP transcription factors, leading to their ubiquitination, decreased protein stability, and rapid degradation, thereby inhibiting lipid and cholesterol synthesis.
Fasting or using SIRT1-activating compounds (like resveratrol or specific activators studied in the paper) can inhibit the production of fats and cholesterol by directly targeting the SREBP proteins responsible for fat synthesis. This happens through a process where SIRT1 removes acetyl groups from SREBP, marking it for destruction, thereby reducing lipid storage.
Our data reveal that SIRT1 can directly deacetylate SREBP, and modulation of SIRT1 activity results in changes in SREBP ubiquitination, protein stability, and target gene expression.
Why this rating
Strong evidence across multiple models (C. elegans, Drosophila, mice, human cell lines) with direct biochemical proof of deacetylation and in vivo efficacy of activators.
Source
Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP
Amy K. Walker et al. · Genes & Development · 2010
DOI 10.1101/gad.1901210
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