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| Status |
Public on Aug 10, 2021 |
| Title |
RNA-sequencing reveals niche gene expression effects of beta-hydroxybutyrate in primary myotubes |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Various forms of fasting, including time-restricted feeding, alternate day fasting, and periodic fasting have shown promise in clinical and pre-clinical studies to normalize body weight, improve metabolic health, and protect against disease. Recent studies suggest that β-hydroxybutyrate (βOHB), a characteristic ketone body of the fasted metabolic state, acts as a potential signaling molecule mediating the beneficial effects of the various forms of fasting, potentially by acting as a histone deacetylase inhibitor. In the first part we investigated whether βOHB, in comparison to the well-established histone deacetylase inhibitor butyrate, influences cellular differentiation in vitro. In C2C12 myotubes, 3T3-L1 adipocytes, and THP-1 monocytes, millimolar concentrations of βOHB did not alter differentiation, as determined by gene expression and histological assessment, whereas equimolar concentrations of butyrate potently impaired differentiation in all cell types. RNA-sequencing revealed that unlike butyrate, βOHB minimally impacted gene expression in adipocytes, macrophages, and hepatocytes. However, in myocytes, βOHB upregulated genes involved in the TCA cycle and oxidative phosphorylation, while downregulating 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 in adipocytes, macrophages and hepatocytes, but suggest that βOHB may act as a niche signaling molecule in muscle.
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| Overall design |
Mouse primary cells (adipocytes, macrophages, skeletal myotubes, hepatocytes) were exposed to β-hydroxybutyric acid (bOHB; 5mM), butyric acid (5mM), or control treatment, and subjected to gene expression profiling by RNA-sequencing.
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| Contributor(s) |
Ruppert PM, Deng L, Hooiveld GJ, Hangelbroek RW, Zeigerer A, Kersten S |
| Citation(s) |
34407998 |
| Submission date |
Jun 28, 2021 |
| Last update date |
Aug 24, 2021 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
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| Samples (36)
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| GSM5403816 |
primary adipocytes, control treatment, replicate 1 |
| GSM5403817 |
primary adipocytes, control treatment, replicate 2 |
| GSM5403818 |
primary adipocytes, control treatment, replicate 3 |
| GSM5403819 |
primary adipocytes, bOHB treatment, replicate 1 |
| GSM5403820 |
primary adipocytes, bOHB treatment, replicate 2 |
| GSM5403821 |
primary adipocytes, bOHB treatment, replicate 3 |
| GSM5403822 |
primary adipocytes, butyric acid treatment, replicate 1 |
| GSM5403823 |
primary adipocytes, butyric acid treatment, replicate 2 |
| GSM5403824 |
primary adipocytes, butyric acid treatment, replicate 3 |
| GSM5403825 |
primary macrophages, control treatment, replicate 1 |
| GSM5403826 |
primary macrophages, control treatment, replicate 2 |
| GSM5403827 |
primary macrophages, control treatment, replicate 3 |
| GSM5403828 |
primary macrophages, bOHB treatment, replicate 1 |
| GSM5403829 |
primary macrophages, bOHB treatment, replicate 2 |
| GSM5403830 |
primary macrophages, bOHB treatment, replicate 3 |
| GSM5403831 |
primary macrophages, butyric acid treatment, replicate 1 |
| GSM5403832 |
primary macrophages, butyric acid treatment, replicate 2 |
| GSM5403833 |
primary macrophages, butyric acid treatment, replicate 3 |
| GSM5403834 |
primary skeletal myotubes, control treatment, replicate 1 |
| GSM5403835 |
primary skeletal myotubes, control treatment, replicate 2 |
| GSM5403836 |
primary skeletal myotubes, control treatment, replicate 3 |
| GSM5403837 |
primary skeletal myotubes, bOHB treatment, replicate 1 |
| GSM5403838 |
primary skeletal myotubes, bOHB treatment, replicate 2 |
| GSM5403839 |
primary skeletal myotubes, bOHB treatment, replicate 3 |
| GSM5403840 |
primary skeletal myotubes, butyric acid treatment, replicate 1 |
| GSM5403841 |
primary skeletal myotubes, butyric acid treatment, replicate 2 |
| GSM5403842 |
primary skeletal myotubes, butyric acid treatment, replicate 3 |
| GSM5403843 |
primary hepatocytes, control treatment, replicate 1 |
| GSM5403844 |
primary hepatocytes, control treatment, replicate 2 |
| GSM5403845 |
primary hepatocytes, control treatment, replicate 3 |
| GSM5403846 |
primary hepatocytes, bOHB treatment, replicate 1 |
| GSM5403847 |
primary hepatocytes, bOHB treatment, replicate 2 |
| GSM5403848 |
primary hepatocytes, bOHB treatment, replicate 3 |
| GSM5403849 |
primary hepatocytes, butyric acid treatment, replicate 1 |
| GSM5403850 |
primary hepatocytes, butyric acid treatment, replicate 2 |
| GSM5403851 |
primary hepatocytes, butyric acid treatment, replicate 3 |
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| Relations |
| BioProject |
PRJNA741937 |
| SRA |
SRP325858 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE179023_TxImport.GeneLevel.counts.GEO.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
| GSE179023_txi.counts.annotated.GEO.Rdata.gz |
19.2 Mb |
(ftp)(http) |
RDATA |
| GSE179023_txi.lengthScaledTPM.annotated.GEO.Rdata.gz |
22.3 Mb |
(ftp)(http) |
RDATA |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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