title: Lysine acetylation in obesity, diabetes and metabolic disease.
abstract: Histone acetyltransferases (HATs) and histone deacetylases (HDACs) mediate acetylation and deacetylation of histone proteins and transcription factors. There is abundant evidence that these enzymes regulate the acetylation state of many cytoplasmic proteins, including lysine residues in important metabolic enzymes. Lysine acetylation regulates major cellular functions as a common post-transcriptional modification of proteins, conserved from prokaryotes to humans. In this article, we refer to HATs and HDACs broadly as lysine acetyltransferases (KATs) and deacetylases (KDACs). Lysine acetylation is vitally important in both immunological and metabolic pathways and may regulate the balance between energy storage and expenditure. Obesity, type II diabetes and cardiovascular disease (metabolic syndrome) are widely recognised as features of a chronic low-grade inflammatory state, involving significant alterations in primary immunometabolism. Identifying effective therapeutic and preventive options to treat this multi-factorial syndrome has proven to be very challenging, with an emerging focus on developing anti-inflammatory agents that can combat adiposity and metabolic disease. Here, we summarise current evidence and understanding of innate immune and metabolic pathways relevant to adiposity and metabolic disease regulated by lysine acetylation. Developing this understanding in greater detail may facilitate strategic development of novel and enzyme-specific lysine deacetylase modulators that regulate both metabolic and immune systems.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. a.iyer@imb.uq.edu.au
authors.forename: Abishek
authors.initials: A
authors.lastname: Iyer
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000276:immunology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000276:immunology; D051548:Histone Acetyltransferases / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009765:Obesity / Q000276:immunology / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D008239:Lysine