Parental micronutrient deficiency distorts liver DNA methylation and expression of lipid genes associated with a fatty-liver-like phenotype in offspring

• DOI: 10.1038/s41598-018-21211-5
• Publication Date: 2018-02-08T16:31:58Z
• Authors: Kaja H. Skjærven; Lars Martin Jakt; Jorge M. O. Ferna...; John Arne Dahl; Anne-Catrin Adam; Johanna Klughammer; Christoph Bock; Marit Espe
• Keywords: Male; 0301 basic medicine; VDP::Matematikk og Naturvitenskap: 400::Basale biofag: 470::Genetikk og genomikk: 474; Gene Expression; Article; Epigenesis, Genetic; 03 medical and health sciences; Folic Acid; Methionine; Pregnancy; Animals; Micronutrients; Zebrafish; 2. Zero hunger; DNA Methylation; Lipid Metabolism; Vitamin B 6; Diet; Fatty Liver; Vitamin B 12; Animals, Newborn; Liver; Prenatal Exposure Delayed Effects; Dietary Supplements; Female

Abstract Micronutrient status of parents can affect long term health their progeny. Around 2 billion humans are affected by chronic micronutrient deficiency. In this study we use zebrafish as a model system to examine morphological, molecular and epigenetic changes in mature offspring that experienced one-carbon (1-C) Zebrafish were fed diet sufficient, or marginally deficient 1-C nutrients (folate, vitamin B12, B6, methionine, choline), then mated. Offspring livers underwent histological examination, RNA sequencing genome-wide DNA methylation analysis. Parental deficiency resulted increased lipid inclusion identified 686 differentially expressed genes liver, the majority which downregulated. Downregulated enriched for functional categories related sterol, steroid biosynthesis, well mitochondrial protein synthesis. Differential was found at 2869 CpG sites, promoter regions permutation analyses confirmed association with parental feed. Our data indicate nutrient persist locus specific marks descendants suggest an effect on utilization translation F 1 livers. This points toward micronutrients important factor welfare.