Endocrine Abstracts (2019) 65 P187 | DOI: 10.1530/endoabs.65.P187

Low B12 is associated with increased de novo synthesis of 'unsafe' fatty acids in the liver

Joseph Boachie1, Antonysunil Adaikalakoteswari1,2, Jinus Samavat1 & Ponnusamy Saravanan1,3


1Division of Metabolic and Vascular Health, Clinical Sciences Research Laboratories, Warwick Medical School, University of Warwick, Coventry, UK; 2Interdisciplinary Science and Technology Centre, School of Science and Technology, Nottingham Trent University, Clifton, Nottingham, UK; 3Diabetes Centre, George Eliot Hospital NHS Trust College Street, Nuneaton, Warwickshire, Nuneaton, UK


Background: Vitamin B12 (B12) deficiency is associated with obesity and was recently shown to trigger lipid accumulation in the adipose tissues and liver. The body is capable of synthesizing fatty acids (FAs) endogenously via de novo lipogenesis in the liver. However, dysregulated levels are associated with adverse consequences in subjects. We therefore assessed B12 regulation of de novo fatty acid synthesis and the profile of various FAs in hepatocytes.

Methods: Hep G2 cell line was cultured using custom-made B12 deficient EMEM media and seeded in four concentrations of B12 media such as 500 nM (control), 1000 pM, 100 pM and 25 pM (low) B12 until reaching 100% confluence. Oil Red O (ORO) staining, RT-qPCR and gas chromatography were employed to examine the effect of B12 deficiency on de novo synthesis and profile of FAs in hepatocytes.

Results: Hepatocytes in low B12 (25 pM) had more lipid droplets compared to control B12 (500 nM). The master regulator SREBF1 and enzymes of de novo FA synthesis (ACLY, ACC, FASN, ELOVL6 and SCD1) were increased under low B12. Total FA level was significantly higher in low B12 than control. Low B12 increased levels of SFAs, MUFAs, trans-FA and PUFAn-6/n-3 ratio but had no significant effect on PUFA-total compared to control. Among individual FAs, even chains such as palmitate (C16), stearate (C18) and oleate (C18:1 n-9) were higher and minimal levels of odd chains such as margaric acid (C17), heneicosylic acid (C21) and tricosylic acid (C23) that were also upregulated in low B12 than control.

Conclusion: Our study provides novel evidence that vitamin B12 deficiency (1) upregulates hepatic de novo FA synthesis dominated by SFAs, (2) increases levels of even-chain SFA (C12, C14, C16, C18), odd-chain SFA (C17, C21 and C23), MUFA (C18:1n-9 and C18:1 n-7), TFAs (C16:1t and C18:1t) and had no effect on PUFA-total compared to control.

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