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Carrer A, Parris JL, Trefely S, Henry RA, Montgomery DC, Torres A, Viola JM, Kuo YM, Blair IA, Meier JL, Andrews AJ, Snyder NW, Wellen KE
Impact of High Fat Diet on Tissue Acyl-CoA and Histone Acetylation Levels
J Biol Chem (2017) 292:3312-3322.
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood, but could alter gene expression and influence metabolic health. ATP-citrate lyase (ACLY) produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high fat diet (HFD) results in suppression of ACLY levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown. Here we examined the effects of HFD on levels of acyl-CoAs and histone acetylation in mouse white adipose tissue (WAT), liver, and pancreas. We report that in mice, consuming a HFD reduced levels of acetyl-CoA and/or the acetyl-CoA: CoA ratio in these tissues. In WAT and pancreas, HFD also impacted levels of histone acetylation; in particular, histone H3 lysine 23 acetylation (H3K23ac) was lower in HFD-fed mice. Genetic deletion of Acly in cultured adipocytes also suppressed acetyl-CoA and histone acetylation levels. In liver, no significant effects on histone acetylation were observed with HFD, despite lower acetyl-CoA levels. Intriguingly, acetylation of several histone lysines correlated with the acetyl-CoA: (iso)butyryl-CoA ratio in liver. Butyryl-CoA and isobutyryl-CoA interacted with the acetyltransferase PCAF in liver lysates and inhibited its activity in vitro. This study thus provides evidence that diet can impact tissue acyl-CoA and histone acetylation levels, and that acetyl-CoA abundance correlates with acetylation of specific histone lysines in WAT but not in liver.
Publication Date: 2017-02-24.
PMCID: PMC5336165
Last updated on Tuesday, August 11, 2020