{"doi":"10.1111/liv.14811","title":"Maternal high‐fat diet disrupted one‐carbon metabolism in offspring, contributing to nonalcoholic fatty liver disease","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.","journal":"Liver International","year":2021,"id":166553,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":33,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":693130,"name":"Huiting Xu","orcid":null,"position":1,"is_corresponding":false},{"id":692313,"name":"Jie Wu","orcid":"0000-0002-9877-1764","position":2,"is_corresponding":false},{"id":692314,"name":"Jiangyuan Li","orcid":"0000-0001-9983-1119","position":3,"is_corresponding":false},{"id":370804,"name":"Yi Zhou","orcid":"0000-0002-9860-5010","position":4,"is_corresponding":false},{"id":525788,"name":"Zehuan Ding","orcid":"0000-0001-5068-6598","position":5,"is_corresponding":false},{"id":692315,"name":"Stefan Siwko","orcid":"0000-0003-4260-2985","position":6,"is_corresponding":false},{"id":692316,"name":"Xianglin Yuan","orcid":"0000-0003-4653-5388","position":7,"is_corresponding":false},{"id":692317,"name":"Kevin L. Schalinske","orcid":"0000-0001-5910-8719","position":8,"is_corresponding":false},{"id":257786,"name":"Gianfranco Alpini","orcid":"0000-0002-6658-3021","position":9,"is_corresponding":false},{"id":370808,"name":"Ke Zhang","orcid":"0000-0002-7130-3215","position":10,"is_corresponding":false},{"id":370809,"name":"Linglin Xie","orcid":"0000-0003-4018-3801","position":11,"is_corresponding":false},{"id":692312,"name":"Hui Peng","orcid":"0000-0002-8901-1384","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:45:49.644768Z","pmid":"33529448","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}