title: Folate depletion changes gene expression of fatty acid metabolism, DNA synthesis, and circadian cycle in male mice.
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.
authors.affiliation: INSERM U1028, CNRS UMR5292, Université Lyon 1, Centre de Recherche en Neurosciences, Neurooncologie et Neuroinflammation, Fac Med Laennec, F-69372 Lyon, Cedex 08, France. champier@sante.univ-lyon1.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Champier
authors.forename: Francine
authors.initials: F
authors.lastname: Claustrat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nazaret
authors.forename: Michelle
authors.initials: M
authors.lastname: Fèvre Montange
authors.forename: Bruno
authors.initials: B
authors.lastname: Claustrat
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D019175:DNA Methylation; D004261:DNA Replication / Q000235:genetics*; D003624:Darkness; D005227:Fatty Acids; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000150:complications / Q000235:genetics*; D015870:Gene Expression; D006710:Homocysteine / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000209:etiology; D008027:Light; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010711:Phosphatidate Phosphatase / Q000235:genetics / Q000378:metabolism; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D005227:Fatty Acids; D009687:Nuclear Proteins; D006710:Homocysteine; D014803:Vitamin B Complex; D004247:DNA; D005492:Folic Acid; C418978:Lpin1 protein, mouse; D010711:Phosphatidate Phosphatase; D008550:Melatonin