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Vitamin B12 induces hepatic fatty infiltration through altered fatty acid metabolism
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Boachie, Joseph, Adaikalakoteswari, Antonysunil, Gázquez, Antonio, Zammit, Victor A., Larqué, Elvira and Saravanan, Ponnusamy (2021) Vitamin B12 induces hepatic fatty infiltration through altered fatty acid metabolism. Cellular Physiology and Biochemistry, 55 (3). pp. 241-255. 000368. doi:10.33594/000000368 ISSN 1015-8987.
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Official URL: https://doi.org/10.33594/000000368
Abstract
Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.
| Item Type: | Journal Article | |||||||||||||||
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| Subjects: | R Medicine > RC Internal medicine | |||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Vitamin B12 deficiency, Lipids -- Metabolism -- Disorders, Fatty acids -- Metabolism -- Disorders, Diabetes, Fatty acids -- Oxidation | |||||||||||||||
| Journal or Publication Title: | Cellular Physiology and Biochemistry | |||||||||||||||
| Publisher: | Karger | |||||||||||||||
| ISSN: | 1015-8987 | |||||||||||||||
| Official Date: | 2021 | |||||||||||||||
| Dates: |
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| Volume: | 55 | |||||||||||||||
| Number: | 3 | |||||||||||||||
| Page Range: | pp. 241-255 | |||||||||||||||
| Article Number: | 000368 | |||||||||||||||
| DOI: | 10.33594/000000368 | |||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||
| Publication Status: | Published | |||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
| Date of first compliant deposit: | 23 April 2021 | |||||||||||||||
| Date of first compliant Open Access: | 21 May 2021 | |||||||||||||||
| RIOXX Funder/Project Grant: |
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