Maternal high-fat diet disrupted one-carbon metabolism in offspring, contributing to nonalcoholic fatty liver disease.
Liver Int
; 41(6): 1305-1319, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33529448
ABSTRACT
BACKGROUND & AIMS:
Pregnant women may transmit their metabolic phenotypes to their offspring, enhancing the risk for nonalcoholic fatty liver disease (NAFLD); however, the molecular mechanisms remain unclear.METHODS:
Prior to pregnancy female mice were fed either a maternal normal-fat diet (NF-group, "no effectors"), or a maternal high-fat diet (HF-group, "persistent effectors"), or were transitioned from a HF to a NF diet before pregnancy (H9N-group, "effectors removal"), followed by pregnancy and lactation, and then offspring were fed high-fat diets after weaning. Offspring livers were analysed by functional studies, as well as next-generation sequencing for gene expression profiles and DNA methylation changes.RESULTS:
The HF, but not the H9N offspring, displayed glucose intolerance and hepatic steatosis. The HF offspring also displayed a disruption of lipid homeostasis associated with an altered methionine cycle and abnormal one-carbon metabolism that caused DNA hypermethylation and L-carnitine depletion associated with deactivated AMPK signalling and decreased expression of PPAR-α and genes for fatty acid oxidation. These changes were not present in H9N offspring. In addition, we identified maternal HF diet-induced genes involved in one-carbon metabolism that were associated with DNA methylation modifications in HF offspring. Importantly, the DNA methylation modifications and their associated gene expression changes were reversed in H9N offspring livers.CONCLUSIONS:
Our results demonstrate for the first time that maternal HF diet disrupted the methionine cycle and one-carbon metabolism in offspring livers which further altered lipid homeostasis. CpG islands of specific genes involved in one-carbon metabolism modified by different maternal diets were identified.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Efeitos Tardios da Exposição Pré-Natal
/
Hepatopatia Gordurosa não Alcoólica
Limite:
Animals
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos