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bioRxiv · 10.1101/263426

Multi-Omic Profiling Reveals the Opposing Forces of Excess Dietary Sugar and Fat on Liver Mitochondria Protein Acetylation and Succinylation

Meyer, J. G.·Softic, S.·Basisty, N.·Rardin, M. J.·Verdin, E.·Gibson, B. W.·Ilkayeva, O.·Newgard, C.·Kahn, C. R.·Schilling, B.
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Abstract

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.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/263426_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (53K):\norg.highwire.dtl.DTLVardef@1419c64org.highwire.dtl.DTLVardef@82a874org.highwire.dtl.DTLVardef@16023org.highwire.dtl.DTLVardef@4ed44e_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract\n\nC_FIG

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Meyer, J. G., Softic, S., Basisty, N., Rardin, M. J., Verdin, E., Gibson, B. W., Ilkayeva, O., Newgard, C., Kahn, C. R., Schilling, B.. 2018-02-10. Multi-Omic Profiling Reveals the Opposing Forces of Excess Dietary Sugar and Fat on Liver Mitochondria Protein Acetylation and Succinylation. https://doi.org/10.1101/263426

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