High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring.
Mol Metab
; 5(3): 184-197, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26977389
ABSTRACT
OBJECTIVES:
Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring.METHODS:
F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing.RESULTS:
Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets.CONCLUSION:
Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Mol Metab
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Suécia