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| Status |
Public on Oct 21, 2013 |
| Title |
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
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| Overall design |
Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.
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| Contributor(s) |
den Besten G, Lange K, Hooiveld GJ, Reijngoud DJ |
| Citation(s) |
24136789 |
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| Submission date |
Apr 09, 2013 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
[email protected]
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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) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA196648 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45926_RAW.tar |
17.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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