Lipids Reprogram Metabolism to Become a Major Carbon Source for Histone Acetylation

• DOI: 10.1016/j.celrep.2016.10.012
• Publication Date: 2016-11-01T16:30:34Z
• Authors: Eoin McDonnell; Scott B. Crown; Douglas B. Fox; Betül Kitir; Olga R. Ilkayeva; Christian A. Olsen; Paul A. Grimsrud; Matthew D. Hirschey
• Keywords: 0301 basic medicine; QH301-705.5; histone; lipids; Histones; Mice; 03 medical and health sciences; proteomics; Acetyl Coenzyme A; Cell Line, Tumor; Animals; Humans; Amino Acid Sequence; Biology (General); acetylation; epigenetics; Gene Expression Profiling; Acetylation; Lipid Metabolism; metabolomics; Carbon; Histone Deacetylase Inhibitors; Gene Expression Regulation; gene expression; fatty acid; Caprylates; metabolism; Oxidation-Reduction

Highlights•Fatty acid oxidation increases global histone acetylation•Lipids can provide up to 90% of acetyl-carbon for acetylation•Octanoate reprograms metabolism and becomes the major source acetyl-CoA•Lipid-derived acetyl-CoA promotes lipid-specific gene expressionSummaryCells integrate nutrient sensing coordinate proper cellular responses a particular source. For example, glucose drives expression program characterized by activating genes involved in its metabolism, part increasing glucose-derived acetylation. Here, we find that lipid-derived is carbon Using 13C-carbon tracing combined with acetyl-proteomics, show acetylation on certain lysines be derived from fatty carbon, even presence excess glucose. By repressing both glutamine leading increased acetyl-CoA. Gene profiling octanoate-treated hepatocytes shows pattern upregulated lipid metabolic genes, demonstrating specific transcriptional response lipid. These studies expand landscape uncover how lipids are integrated epigenetic events control expression.Graphical abstract