Temporal dynamics of liver mitochondrial protein acetylation and succinylation and metabolites due to high fat diet and/or excess glucose or fructose

Dietary macronutrient composition alters metabolism through several mechanisms, including post-translational modification (PTM) of proteins. To connect diet and molecular changes, here we performed short- and long-term feeding of mice with standard chow diet (SCD) and high-fat diet (HFD), with or wi...

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Vydané v:PloS one Ročník 13; číslo 12; s. e0208973
Hlavní autori: Meyer, Jesse G., Softic, Samir, Basisty, Nathan, Rardin, Matthew J., Verdin, Eric, Gibson, Bradford W., Ilkayeva, Olga, Newgard, Christopher B., Kahn, C. Ronald, Schilling, Birgit
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 26.12.2018
Public Library of Science (PLoS)
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ISSN:1932-6203, 1932-6203
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Shrnutí:Dietary macronutrient composition alters metabolism through several mechanisms, including post-translational modification (PTM) of proteins. To connect diet and molecular changes, here we performed short- and long-term feeding of mice with standard chow diet (SCD) and high-fat diet (HFD), with or without glucose or fructose supplementation, and quantified liver metabolites, 861 proteins, and 1,815 protein level-corrected mitochondrial acetylation and succinylation sites. Nearly half the acylation sites were altered by at least one diet; nutrient-specific changes in protein acylation sometimes encompass entire pathways. Although acetyl-CoA is an intermediate in both sugar and fat metabolism, acetyl-CoA had a dichotomous fate depending on its source; chronic feeding of dietary sugars induced protein hyperacetylation, whereas the same duration of HFD did not. Instead, HFD resulted in citrate accumulation, anaplerotic metabolism of amino acids, and protein hypo-succinylation. Together, our results demonstrate novel connections between dietary macronutrients, protein post-translational modifications, and regulation of fuel selection in liver.
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Competing Interests: The authors have declared that no competing interests exist.
Current address: Department of Chemistry, Department of Biomolecular Chemistry, National Center for Quantitative Biology of Complex Systems, University of Wisconsin–Madison, Madison, Wisconsin, United States of America
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0208973