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

Pessoa Rodrigues, C., Chatterjee, A., Wiese, M., Stehle, T., Szymanski, W. G., Shvedunova, M., et al. (2021). Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice. Nature Communications, 12: 6212. doi:10.1038/s41467-021-26277-w.

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Pessoa et al. 2021_3.pdf (Publisher version), 11MB
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Pessoa Rodrigues, Cecilia1, Author
Chatterjee, Aindrila1, Author
Wiese, Meike1, Author
Stehle, Thomas1, Author
Szymanski, Witold G.2, Author              
Shvedunova, Maria1, Author
Akhtar, Asifa1, Author              
Affiliations:
1Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243643              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243640              

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 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.

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Language(s): eng - English
 Dates: 2021-10-27
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-021-26277-w
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 Sequence Number: 6212 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723