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| Status |
Public on Dec 30, 2012 |
| Title |
Folate and vitamin B12 imbalance induces endoplasmic reticulum stress and cholesterol biosynthesis gene expression in human adipocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: Low B12 has been shown to play an important role in the prediction of metabolic risk, but its significance and mechanism in the development of adiposity and adipose tissue dysfunction is largely unknown.
Objective: To investigate the role of B12 and folic acid in the development of adipocyte dysfunction.
Methods and Results: Microarray analysis of human adipocytes (CHUB-S7 cell line) cultured and differentiated in customised media with varying concentrations of B12 and folic acid led to the identification of two important pathways: cholesterol synthesis and unfolded protein response (UPR). Adipocytes cultured in media with low B12 (150 pmol/L) or no B12 had increased intracellular total cholesterol, higher secreted homocysteine levels, induced UPR and reduced glucose uptake capacity compared to adipocytes cultured in normal media with higher B12. The folate concentrations had either no or little effect on the measured functions. Further analysis of these adipocytes for overall DNA methylation showed that the promoter regions of sterol regulatory element-binding transcription factor 1 (SREBF1) and low density lipoprotein receptor (LDLR) were hypomethylated in the low and no B12 conditions. The SREB proteins (SREBP1 and 2) and mRNA expressions (SREBF1 and LDLR) were also increased in the same conditions.
Conclusion: The data suggest that low B12 can lead to adipocyte dysfunction by inducing excess cholesterol biosynthesis, homocysteine production and induction of UPR and overall adipocyte dysfunction. Both of these pathways and adipocyte dysfunction play a significant role in the development of cardiovascular diseases.
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| Overall design |
Independent replicate samples of the human adipocyte cell line CHUB-S7 were treated with four different concentrations of B12 and folate.
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| Contributor(s) |
Adaikalakoteswari A, McCarthy CM, Moore JD, Voyias PD, Harte AL, McTernan PG, Kumar S, Saravanan P, Tripathi G |
| Citation(s) |
25763114 |
| Submission date |
Dec 27, 2012 |
| Last update date |
Oct 11, 2016 |
| Contact name |
Jonathan David Moore |
| E-mail(s) |
jonathan.moore@tgac.ac.uk
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| Organization name |
The Genome Analysis Centre
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| Department |
Platforms and Pipelines
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| Street address |
Norwich Research Park
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| City |
Norwich |
| ZIP/Postal code |
NR4 7UH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (15)
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| GSM1057745 |
CHUB-S7, no B12, no folate; 1 |
| GSM1057746 |
CHUB-S7, no B12, no folate; 2 |
| GSM1057747 |
CHUB-S7, no B12, no folate; 3 |
| GSM1057748 |
CHUB-S7, B12-0nM, folate-30uM; 1 |
| GSM1057749 |
CHUB-S7, B12-0nM, folate-30uM; 2 |
| GSM1057750 |
CHUB-S7, B12-0nM, folate-30uM; 3 |
| GSM1057751 |
CHUB-S7, B12-0nM, folate-60uM; 2 |
| GSM1057752 |
CHUB-S7, B12-0nM, folate-60uM; 3 |
| GSM1057753 |
CHUB-S7, B12-50uM, folate-0uM; 1 |
| GSM1057754 |
CHUB-S7, B12-50uM, folate-0uM; 2 |
| GSM1057755 |
CHUB-S7, B12-50uM, folate-0uM; 3 |
| GSM1057756 |
CHUB-S7, B12-500nM, folate-6uM; 4 |
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| Relations |
| BioProject |
PRJNA184810 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43166_RAW.tar |
46.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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