Measuring acetyl-coa and acetylated histone turnover in vivo: Effect of a high fat diet.

Measuring acetyl-coa and acetylated histone turnover in vivo: Effect of a high fat diet.

Arias-Alvarado A; Aghayev M; Ilchenko S; Rachdaoui N; Lepp J; Tsai T-H; Zhang G-F; Previs S; Kasumov T

Analytical Biochemistry

2021

2021-02-15

Cellular availability of acetyl-CoA, a central intermediate of metabolism, regulates histone acetylation. The impact of a high-fat diet (HFD) on the turnover rates of acetyl-CoA and acetylated histones is unknown. We developed a method for simultaneous measurement of acetyl-CoA and acetylated histones kinetics using a single (2)H(2)O tracer, and used it to examine effect of HFD-induced perturbations on hepatic histone acetylation in LDLR(-/-) mice, a mouse model of non-alcoholic fatty liver disease (NAFLD). Mice were given (2)H(2)O in the drinking water and the kinetics of hepatic acetyl-CoA, histones, and acetylated histones were quantified based on their (2)H-labeling. Consumption of a high fat Western-diet (WD) for twelve weeks led to decreased acetylation of hepatic histones (p< 0.05), as compared to a control diet. These changes were associated with 1.5-3-fold increased turnover rates of histones without any change in acetyl-CoA flux. Acetylation significantly reduced the stability of histones and the turnover rates of acetylated peptides were correlated with the number of acetyl groups in neighboring lysine sites. We conclude that (2)H(2)O-method can be used to study metabolically controlled histone acetylation and acetylated histone turnover in vivo.

Acetyl-CoA; Acetylation; Heavy water; High resolution mass spectrometry; Histone; Turnover

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journalArticle

114067

615

1096-0309 0003-2697

NEOMED College of Pharmacy

Department of Pharmaceutical Sciences

January 2021 List