Nutritional B vitamin deficiency disrupts lipid metabolism causing accumulation of proatherogenic lipoproteins in the aorta adventitia of ApoE null mice

Abstract

Scope: Cardiovascular disease is the major cause of death in the world. Low dietary folate, elevated homocysteine, and high circulating cholesterol are risk factors. Methods and results:We investigated whether folate and/or B vitamin deficiency would change lipoprotein and fatty acid metabolism and lipid accumulation in the aorta adventitia of ApoE null mice. Mice (n = 10 per group) were fed a control (C; 4%) or high saturated fat (HF; 21%), and high cholesterol (0.15%) diet for 16 weeks. Folate (F-) or folate, B6 and B12 deficiency (F-B-) were imposed on these diets. Feeding a HF diet increased plasma and liver total cholesterol and HDL cholesterol (two-to threefold; p < 0.05). Total cholesterol increased (twofold; p < 0.05) in aorta adventitial lipid in response to HF. Feeding a diet depleted of folate and B vitamins (F-B-) significantly increased cholesterol accumulation in both liver and aorta adventitial lipid (approximately 50-70%; p < 0.05). Moreover, the proportions of fatty acids in hepatic and adventitial lipid was significantly changed by B vitamin depletion, measured as an increase in saturated fatty acids (approximately 15%) and a decrease (approximately 11%) in monounsaturated fatty acids (p < 0.05). Conclusion: B vitamin deficiency perturbs lipid metabolism in ApoE null mice, causing accumulation of proatherogenic cholesterol and fatty acids in the aorta adventitia. Keywords:B vitamin deficiency in ApoE null mice / Hyperhomocysteinemia / Lipid metabolism / Vascular lipid deposition

Nutritional B vitamin deficiency alters the expression of key proteins associated with vascular smooth muscle cell proliferation and migration in the aorta of atherosclerotic apolipoprotein E null mice

“…The design of this animal study and the composition of the experimental diets employed have been described in detail elsewhere (McNeil et al 2011(McNeil et al , 2012. All procedures were carried out in accordance with the requirements of the UK Animals (Scientific Procedures) Act 1986.…”

“…The aortic arch was fixed in 10 % formalin and atherosclerotic plaque volume quantified by staining plaques in situ with the neutral lipid-targeting lysochrome Oil Red O (ORO, Sigma, Poole, UK), which targets fatty acid deposits in the arterial plaques and solubilising and measuring spectrophotometrically the dye retained in the aorta. Solubilised ORO as a biomarker of atherosclerotic plaque volume was corrected for aorta tissue weight (Beattie et al 2009;McNeil et al 2011McNeil et al , 2012.…”

“…Blood and tissue folate and B 12 were measured by radioassay and plasma total homocysteine by gas chromatography (McNeil et al 2011(McNeil et al , 2012. Lipid was extracted from adventitial tissue (approx.…”

“…We have developed distinct nutritional deficiencies in transgenic ApoE null mice so that they exhibit either mild or moderate hyperhomocysteinemia (McNeil et al 2011). We have shown that B vitamin deficiency increases atherosclerotic plaque formation in transgenic ApoE knockout mice and that this is strongly linked with accumulation of cholesterol and pro-atherogenic lipoproteins in the adventitial lipid surrounding the aorta (McNeil et al 2011(McNeil et al , 2012.…”

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats

“…Biotin deficiency induces an abnormality in fatty acid metabolism (18). Thus, it is clear that B-group vitamin deficiencies disrupt lipid metabolism (19). These reports seem to indicate some relationship between orotic acid-induced fatty livers and B-group vitamin concentrations in the liver.…”