Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice

Cecilia Pessoa Rodrigues, Aindrila Chatterjee, Meike Wiese, Thomas Stehle, Witold Szymanski, Maria Shvedunova and Asifa Akhtar ()
Additional contact information
Cecilia Pessoa Rodrigues: Max Planck Institute of Immunobiology and Epigenetics
Aindrila Chatterjee: Max Planck Institute of Immunobiology and Epigenetics
Meike Wiese: Max Planck Institute of Immunobiology and Epigenetics
Thomas Stehle: Max Planck Institute of Immunobiology and Epigenetics
Witold Szymanski: Proteomics Facility, Max Planck Institute of Immunobiology and Epigenetics
Maria Shvedunova: Max Planck Institute of Immunobiology and Epigenetics
Asifa Akhtar: Max Planck Institute of Immunobiology and Epigenetics

Nature Communications, 2021, vol. 12, issue 1, 1-21

Abstract: Abstract Noncommunicable diseases (NCDs) account for over 70% of deaths world-wide. Previous work has linked NCDs such as type 2 diabetes (T2D) to disruption of chromatin regulators. However, the exact molecular origins of these chronic conditions remain elusive. Here, we identify the H4 lysine 16 acetyltransferase MOF as a critical regulator of central carbon metabolism. High-throughput metabolomics unveil a systemic amino acid and carbohydrate imbalance in Mof deficient mice, manifesting in T2D predisposition. Oral glucose tolerance testing (OGTT) reveals defects in glucose assimilation and insulin secretion in these animals. Furthermore, Mof deficient mice are resistant to diet-induced fat gain due to defects in glucose uptake in adipose tissue. MOF-mediated H4K16ac deposition controls expression of the master regulator of glucose metabolism, Pparg and the entire downstream transcriptional network. Glucose uptake and lipid storage can be reconstituted in MOF-depleted adipocytes in vitro by ectopic Glut4 expression, PPARγ agonist thiazolidinedione (TZD) treatment or SIRT1 inhibition. Hence, chronic imbalance in H4K16ac promotes a destabilisation of metabolism triggering the development of a metabolic disorder, and its maintenance provides an unprecedented regulatory epigenetic mechanism controlling diet-induced obesity.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26277-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26277-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26277-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().