PT  - JOURNAL ARTICLE
AU  - Jesse G. Meyer
AU  - Samir Softic
AU  - Nathan Basisty
AU  - Matthew J. Rardin
AU  - Eric Verdin
AU  - Bradford W. Gibson
AU  - Olga Ilkayeva
AU  - Christopher B. Newgard
AU  - C. Ronald Kahn
AU  - Birgit Schilling
TI  - Multi-Omic Profiling Reveals the Opposing Forces of Excess Dietary Sugar and Fat on Liver Mitochondria Protein Acetylation and Succinylation
AID  - 10.1101/263426
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 263426
4099  - http://biorxiv.org/content/early/2018/02/10/263426.short
4100  - http://biorxiv.org/content/early/2018/02/10/263426.full
AB  - 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.Graphical Abstract