Article open access publication

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

Cell Reports, Elsevier, ISSN 2211-1247

Volume 17, 6, 2016

DOI:10.1016/j.celrep.2016.10.012, Dimensions: pub.1023127633, PMC: PMC5123807, PMID: 27806287,

Affiliations

Organisations

  1. (1) Duke University, grid.26009.3d
  2. (2) Duke Medical Center, grid.414179.e
  3. (3) University of Copenhagen, grid.5254.6, KU

Description

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

Funders

Research Categories

Main Subject Area

Fields of Research

Links & Metrics

NORA University Profiles

University of Copenhagen

Danish Open Access Indicator

2016: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2016: Level 2

Research area: Medicine

Dimensions Citation Indicators

Times Cited: 112

Field Citation Ratio (FCR): 18.29

Relative Citation ratio (RCR): 6.06

Open Access Info

Pure Gold