PUBLICATION
Parental micronutrient deficiency distorts liver DNA methylation and expression of lipid genes associated with a fatty-liver-like phenotype in offspring
- Authors
- Skjærven, K.H., Jakt, L.M., Fernandes, J.M.O., Dahl, J.A., Adam, A.C., Klughammer, J., Bock, C., Espe, M.
- ID
- ZDB-PUB-180223-16
- Date
- 2018
- Source
- Scientific Reports 8: 3055 (Journal)
- Registered Authors
- Fernandes, Jorge
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Newborn
- DNA Methylation
- Diet/methods
- Dietary Supplements
- Epigenesis, Genetic
- Fatty Liver/genetics
- Fatty Liver/metabolism
- Female
- Folic Acid/metabolism
- Gene Expression
- Lipid Metabolism
- Liver/drug effects
- Liver/metabolism
- Male
- Methionine/metabolism
- Micronutrients/deficiency*
- Micronutrients/metabolism*
- Pregnancy
- Prenatal Exposure Delayed Effects
- Vitamin B 12/metabolism
- Vitamin B 6/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 29445184 Full text @ Sci. Rep.
Citation
Skjærven, K.H., Jakt, L.M., Fernandes, J.M.O., Dahl, J.A., Adam, A.C., Klughammer, J., Bock, C., Espe, M. (2018) Parental micronutrient deficiency distorts liver DNA methylation and expression of lipid genes associated with a fatty-liver-like phenotype in offspring. Scientific Reports. 8:3055.
Abstract
Micronutrient status of parents can affect long term health of 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 of parents that experienced a one-carbon (1-C) micronutrient deficiency. Zebrafish were fed a diet sufficient, or marginally deficient in 1-C nutrients (folate, vitamin B12, vitamin B6, methionine, choline), and then mated. Offspring livers underwent histological examination, RNA sequencing and genome-wide DNA methylation analysis. Parental 1-C micronutrient deficiency resulted in increased lipid inclusion and we identified 686 differentially expressed genes in offspring liver, the majority of which were downregulated. Downregulated genes were enriched for functional categories related to sterol, steroid and lipid biosynthesis, as well as mitochondrial protein synthesis. Differential DNA methylation was found at 2869 CpG sites, enriched in promoter regions and permutation analyses confirmed the association with parental feed. Our data indicate that parental 1-C nutrient status can persist as locus specific DNA methylation marks in descendants and suggest an effect on lipid utilization and mitochondrial protein translation in F1 livers. This points toward parental micronutrients status as an important factor for offspring health and welfare.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping