RT Journal Article
SR Electronic
T1 RNA sequencing reveals niche gene expression effects of beta-hydroxybutyrate in primary myotubes
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101037
DO 10.26508/lsa.202101037
VO 4
IS 10
A1 Philip MM Ruppert
A1 Lei Deng
A1 Guido JEJ Hooiveld
A1 Roland WJ Hangelbroek
A1 Anja Zeigerer
A1 Sander Kersten
YR 2021
UL https://www.life-science-alliance.org/content/4/10/e202101037.abstract
AB 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.