Maternal High-Fat Diet Disrupted One-Carbon Metabolism in Offspring, contributing to Nonalcoholic Fatty Liver Disease
dc.contributor.author | Peng, Hui | |
dc.contributor.author | Xu, Huiting | |
dc.contributor.author | Wu, Jie | |
dc.contributor.author | Li, Jiangyuan | |
dc.contributor.author | Zhou, Yi | |
dc.contributor.author | Ding, Zehuan | |
dc.contributor.author | Siwko, Stefan K. | |
dc.contributor.author | Yuan, Xianglin | |
dc.contributor.author | Schalinske, Kevin L. | |
dc.contributor.author | Alpini, Gianfranco | |
dc.contributor.author | Zhang, Ke K. | |
dc.contributor.author | Xie, Linglin | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2023-07-10T12:04:55Z | |
dc.date.available | 2023-07-10T12:04:55Z | |
dc.date.issued | 2021 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Peng H, Xu H, Wu J, et al. Maternal high-fat diet disrupted one-carbon metabolism in offspring, contributing to nonalcoholic fatty liver disease. Liver Int. 2021;41(6):1305-1319. doi:10.1111/liv.14811 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/34258 | |
dc.language.iso | en_US | en_US |
dc.publisher | Wiley | en_US |
dc.relation.isversionof | 10.1111/liv.14811 | en_US |
dc.relation.journal | Liver International | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Obesity | en_US |
dc.subject | Methionine | en_US |
dc.subject | SAM transferase | en_US |
dc.subject | Fatty acid oxidation | en_US |
dc.subject | DNA methylation | en_US |
dc.title | Maternal High-Fat Diet Disrupted One-Carbon Metabolism in Offspring, contributing to Nonalcoholic Fatty Liver Disease | en_US |
dc.type | Article | en_US |