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Ruppert, P.M.* ; Deng, L.* ; Hooiveld, G.J.* ; Hangelbroek, R.W.* ; Zeigerer, A. ; Kersten, S.*

RNA sequencing reveals niche gene expression effects of beta-hydroxybutyrate in primary myotubes.

Life Sci. All. 4:e202101037 (2021)

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	Open Access Gold

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Various forms of fasting and ketogenic diet have shown promise in (pre-)clinical studies to normalize body weight, improve metabolic health, and protect against disease. Recent studies suggest that β-hydroxybutyrate (βOHB), a fasting-characteristic ketone body, potentially acts as a signaling molecule mediating its beneficial effects via histone deacetylase inhibition. Here, we have investigated whether βOHB, in comparison to the well-established histone deacetylase inhibitor butyrate, influences cellular differentiation and gene expression. In various cell lines and primary cell types, millimolar concentrations of βOHB did not alter differentiation in vitro, as determined by gene expression and histological assessment, whereas equimolar concentrations of butyrate consistently impaired differentiation. RNA sequencing revealed that unlike butyrate, βOHB minimally impacted gene expression in primary adipocytes, macrophages, and hepatocytes. However, in myocytes, βOHB up-regulated genes involved in the TCA cycle and oxidative phosphorylation, while down-regulating genes belonging to cytokine and chemokine signal transduction. Overall, our data do not support the notion that βOHB serves as a powerful signaling molecule regulating gene expression but suggest that βOHB may act as a niche signaling molecule in myocytes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Chain Fatty-acids; Ketone-bodies; Fuel Metabolism; Glucose; Apoptosis; Insulin; Cells; Brain; Time

ISSN (print) / ISBN 2575-1077

e-ISSN 2575-1077

Journal Life Science Alliance

Quellenangaben Volume: 4, Issue: 10, Article Number: e202101037

Publisher EMBO Press

Publishing Place Heidelberg

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Cancer (IDC)

Grants Netherlands Heart Foundation (CVON ENERGISE grant)