Temporal dynamics of liver mitochondrial protein acetylation and succinylation and metabolites due to high fat diet and/or excess glucose or fructose. PLoS One 2018;13(12):e0208973
Date
12/27/2018Pubmed ID
30586434Pubmed Central ID
PMC6306174DOI
10.1371/journal.pone.0208973Scopus ID
2-s2.0-85059221824 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
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.
Author List
Meyer JG, Softic S, Basisty N, Rardin MJ, Verdin E, Gibson BW, Ilkayeva O, Newgard CB, Kahn CR, Schilling BMESH terms used to index this publication - Major topics in bold
AcetylationAnimals
Citric Acid
Diet, High-Fat
Fatty Liver
Glucose
Humans
Lipid Metabolism
Liver
Mice
Mitochondria
Mitochondria, Liver
Mitochondrial Proteins
Protein Processing, Post-Translational