Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain

Studies with animals support a role for vitamin K (VK) in the biosynthesis of sphingolipids, a class of complex lipids present in high concentrations in the brain. In mice and rats, VK deficiency decreases levels of brain sulfatides and causes behavioral alterations. In light of its heterogeneity and to better understand the role of VK in the brain, we characterized the distribution of the two main VK vitamers, phylloquinone (K-1) and menaquinone-4 (MK-4), in nine distinct brain regions. Weaning female Sprague-Dawley rats (n = 5/dietary group) were fed diets containing either low (L, 80 mug/kg diet), adequate (A, 500 mug/kg diet) or high (H, 2000 mug/kg diet) levels of K-1 for 6 mo. The main form of VK in the brain was MK-4, and it was present in significantly higher concentrations in myelinated regions (the pons medulla and midbrain) than in nonmyelinated regions. Both regional K-1 and MK-4 increased with K-1 intake (P < 0.05). Sphingolipid distribution varied across brain regions (P < 0.001) but was not affected by K-1 intake. In the L and A groups but not the H group, brain MK-4 concentration was positively correlated with the concentrations of sulfatides (L, r = 0.518; A, r = 0.479) and sphingomyelin (L, r = 0.515; A, r = 0.426), and negatively correlated with ganglioside concentration (L, r = -0.398); A, r = -0.353). Sphingolipids are involved in major cellular events such as cell proliferation, differentiation and survival. The strong associations reported here between brain MK-4 and sphingomyelin, sulfatides and gangliosides suggest that this vitamer may play an important role in the brain.