Measuring acetyl-coa and acetylated histone turnover in vivo: Effect of a high fat diet.
Acetyl-CoA; Acetylation; Heavy water; High resolution mass spectrometry; Histone; Turnover
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.
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
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<a href="http://doi.org/10.1016/j.ab.2020.114067" target="_blank" rel="noreferrer noopener">10.1016/j.ab.2020.114067</a>
Effect of a high fat "western type" diet on dynamics of hepatic acetylated mitochondrial proteins in a mouse model of NAFLD
Kasumov T;Arias-Alvarado A;Aghayev M;Ilchenko S;McCullough AJ
Hepatology
2020
2020-11
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<a href="http://doi.org/" target="_blank" rel="noreferrer noopener"></a>
Early pro-inflammatory remodeling of HDL proteome in a model of diet-induced obesity: 2H2O-metabolic labeling-based kinetic approach.
inflammation; NAFLD; proteome dynamics; dyslipidemia; insulin resistance; diet-induced obesity; acute-phase proteins; high-density lipoprotein; high-fat diet
Mice fed a high-fat diet for 12 weeks or longer develop hyperglycemia, insulin resistance, dyslipidemia, and fatty liver. Additionally, a high-fat diet induces inflammation that remodels and affects the anti-inflammatory and antiatherogenic property of the high-density lipoprotein (HDL). However, the precise time course of metabolic disease progression and HDL remodeling remains unclear. Short-term (four weeks) high-fat feeding (60% fat calories) was performed in wild-type male C57BL/6J mice to gain insights into the early metabolic disease processes in conjunction with a HDL proteome dynamics analysis using a heavy water metabolic labeling approach. The high-fat diet-fed mice developed hyperglycemia, impaired glucose tolerance, hypercholesterolemia without hypertriglyceridemia or hepatic steatosis. A plasma HDL proteome dynamics analysis revealed increased turnover rates (and reduced half-lives) of several acute-phase response proteins involved in innate immunity, including complement C3 (12.77 ± 0.81 vs. 9.98 ± 1.20 h, p < 0.005), complement factor B (12.71 ± 1.01 vs. 10.85 ± 1.04 h, p < 0.05), complement Factor H (19.60 ± 1.84 vs. 16.80 ± 1.58 h, p < 0.05), and complement factor I (25.25 ± 1.29 vs. 19.88 ± 1.50 h, p < 0.005). Our findings suggest that an early immune response-induced inflammatory remodeling of the plasma HDL proteome precedes the diet-induced steatosis and dyslipidemia.
Sadana P;Lin Li;Aghayev M;Ilchenko S;Kasumov T
International Journal of Molecular Sciences
2020
2020-10-10
journalArticle
<a href="http://doi.org/10.3390/ijms21207472" target="_blank" rel="noreferrer noopener">10.3390/ijms21207472</a>