Hormonal
SIRT1 regulates lipolysis in adipocytes by deacetylating and activating the transcription factor FoxO1, which directly stimulates the expression of the rate-limiting lipolytic enzyme ATGL.
This research explains the biological mechanism behind how caloric restriction and fasting might promote fat loss: by activating SIRT1, which then turns on the genes responsible for breaking down fat (ATGL). It suggests that lifestyle factors activating SIRT1 (like fasting) work by enhancing this specific genetic pathway rather than just through simple calorie counting.
We conclude, therefore, that SIRT1 controls ATGL transcription primarily by deacetylating FoxO1.
Why this rating
Strong mechanistic evidence using multiple cell models (3T3-L1, HEK293T, MEFs) and genetic manipulation (knockdown, overexpression, dominant-negative mutants).
Source
SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL
Partha Chakrabarti et al. · Journal of Lipid Research · 2011
DOI 10.1194/jlr.m014647
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