Vitamin B-6 restriction impairs fatty acid synthesis in cultured human hepatoma (HepG2) cells

Abstract

Vitamin B-6 deficiency has been reported to alter n-6 and n-3 fatty acid profiles in plasma and tissue lipids; however, the mechanisms underlying such metabolic changes remain unclear. The objective of this study was to determine the effects of vitamin B-6 restriction on fatty acid profiles and fatty acid synthesis in HepG2 cells. Cells were cultured for 6 wk in media with four different vitamin B-6 concentrations (10, 20, 50, and 2,000 nM added pyridoxal, representing deficient, marginal, adequate, and supraphysiological conditions) that induced a range of steady-state cellular concentrations of pyridoxal phosphate. Total cellular lipid content was greatest in the deficient (10 nM pyridoxal) medium. The percentage of arachidonic acid and the ratio of arachidonic acid to linoleic acid in the total lipid fraction were ∼15% lower in vitamin B-6-restricted cells, which suggests that vitamin B-6 restriction affects n-6 fatty acid interconversions. Metabolic flux studies indicated significantly lower fractional synthesis rate of oleic acid and arachidonic acid at 10, 20, and 50 nM pyridoxal, whereas that of eicosapentaenoic acid was lower in the cells cultured in 10 nM pyridoxal. Additionally, relative mRNA expressions of Δ5 and Δ6 desaturases were 40–50% lower in vitamin B-6-restricted cells. Overall, these findings suggest that vitamin B-6 restriction alters unsaturated fatty acid synthesis, particularly n-6 and n-3 polyunsaturated fatty acid synthesis. These results and observations of changes in human plasma fatty acid profiles caused by vitamin B-6 restriction suggest a mechanism by which vitamin B-6 inadequacy influences the cardiovascular risk.

Folate and vitamin B12concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

“…The Δ6 desaturase is a PLPdependent enzyme, required for the interconversion of highunsaturated fatty acids (HUFA) (18) into PUFA such as arachidonic acid (20 : 4 n-6) and DHA (22 : 6 n-3). This was also observed in one in vitro study with cultured cells (48) in which a reduction in vitamin B 6 levels led to changes in the n-3 and n-6 long-chain PUFA profile in parallel with reductions in the rate of the desaturation processes. They also found that concentrations of total FA and PL species were higher in vitamin B 6 -deficient cells, as it was also observed in some studies in rats (49,50) .…”

“…In view of the observed associations, this second pathway is less likely to explain our results, as more consistent associations were found for folate and vitamin B 12 biomarkers than for PLP (vitamin B 6 biomarker). However, it is suggested elsewhere (48) that this pathway is more probable than the first one as SAM concentrations were higher, but SAH was lower in the cultured cells with vitamin B 6 restriction. However, the study did not consider the interaction between folate and vitamin B 12 .…”

Circulating B-Vitamins and Smoking Habits Are Associated with Serum Polyunsaturated Fatty Acids in Patients with Suspected Coronary Heart Disease: A Cross-Sectional Study

“…Low serum concentrations of vitamin B 6 are associated with lower estimated D5D and D6D activity indexes in healthy people [ 43 ], and vitamin B 6 -deficiency has shown to decrease the activity index of D6D in rat liver microsomes [ 44 ]. Moreover, high levels of vitamin B 6 have been reported to increase both D5D- and D6D mRNA levels in HepG2 cells [ 5 ]. These results may suggest that folate and vitamins B 6 and B 12 influence genes and enzymes involved in the metabolism of LCPUFA.…”

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

“…The study on volunteers with marginal nutritional deficiency of vitamin B6 showed decreased plasma concentrations of polyunsaturated fatty acids (PUFA) of the n−6 and n−3 families, whereas the levels of TC, LDL-C, HDL-C, and TAG did not change [ 43 ]. Altered synthesis of unsaturated, particularly n−6 and n−3 PUFA, was proved in cultured human hepatoma (HepG2) cells under the condition of vitamin B-6 restriction [ 44 ]. These changes could participate in mechanisms by which vitamin B-6 inadequacy influences cardiovascular risk [ 44 ].…”