Folate depletion changes gene expression of fatty acid metabolism, DNA synthesis, and circadian cycle in male mice

• Published in: Nutrition research (New York, N.Y.) N.Y.), 2012-02, Vol.32 (2), p.124-132
• Main Authors: Champier, Jacques, Claustrat, Francine, Nazaret, Nicolas, Montange, Michelle Fèvre, Claustrat, Bruno
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Circadian Rhythm - genetics; Clock genes; Darkness; DNA - biosynthesis; DNA Methylation; DNA Replication - genetics; Fatty acid metabolism; Fatty Acids; Feeding. Feeding behavior; Folate deficiency; Folic Acid - administration & dosage; Folic Acid Deficiency - complications; Folic Acid Deficiency - genetics; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Gene Expression; Homocysteine - metabolism; Hyperhomocysteinemia - etiology; Light; Lipid Metabolism - genetics; Liver - metabolism; Male; Melatonin - secretion; Mice; Microarray; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphatidate Phosphatase - genetics; Phosphatidate Phosphatase - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B Complex - administration & dosage
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2011.12.012

Abstract Folate is essential for purine and thymidylate biosynthesis and in methyl transfer for DNA methylation. Folate deficiency alters the secretion of melatonin, a hormone involved in circadian rhythm entrainment, and causes hyperhomocysteinemia because of disruption of homocysteine metabolism. Adverse effects of homocysteine include the generation of free radicals, activation of proliferation or apoptosis, and alteration of gene expression. The liver is an important organ for folate metabolism, and its genome analysis has revealed numerous clock-regulated genes. The variations at the level of their expression during folate deficiency are not known. The aim of our study was to investigate the effects of folate deficiency on gene expression in the mouse liver. A control group receiving a synthetic diet and a folate-depleted group were housed for 4 weeks on a 12-hour/12-hour light/dark cycle. Three mice from each group were euthanized under dim red light at the beginning of the light cycle, and 3, at the beginning of the dark period. Gene expression was studied in a microarray analysis. Of the 53 genes showing modified daily expression in the controls, 52 showed a less marked or no difference after folate depletion. Only 1, lpin1 , showed a more marked difference. Ten genes coding for proteins involved in lipid metabolism did not show a morning/evening difference in controls but did after folate depletion. This study shows that, in the mouse liver, dietary folate depletion leads to major changes in expression of several genes involved in fatty acid metabolism, DNA synthesis, and expression of circadian genes.