Fatty acid synthase coordinates mTOR signaling and histone crotonylation during cardiomyocyte hypertrophy

FASN upregulation is linked to markedly elevated histone crotonylation in hypertrophic mouse hearts and cardiomyocytes, and blocking FASN suppresses both crotonylation and hypertrophic growth.

• Why it matters: Cardiac hypertrophy involves epigenetic control of gene expression, but how lipid metabolism connects to histone crotonylation and hypertrophic signaling is unclear.
• What they did: The study measured FASN expression, mTOR activation, and histone crotonylation in mouse hearts and isolated cardiomyocytes by immunoblotting; FASN was silenced with siRNA or inhibited with TVB-2640, with hypertrophic genes quantified by RT-qPCR and cell size by immunofluorescence.
• The result: FASN inhibition reduced histone crotonylation, hypertrophic gene expression, and cardiomyocyte enlargement, and CUT&RUN-seq/RNA-seq showed FASN-enhanced hypertrophy-associated genes enriched for histone crotonylation marks, with human datasets linking higher FASN to hypertrophy markers in HCM.

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