{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:17:48Z","timestamp":1788589068014,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIDDK 1R01DK112368\u201001"],"award-info":[{"award-number":["NIDDK 1R01DK112368\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Prior to pregnancy female mice were fed either a maternal normal\u2010fat diet (NF\u2010group, \u201cno effectors\u201d), or a maternal high\u2010fat diet (HF\u2010group, \u201cpersistent effectors\u201d), or were transitioned from a HF to a NF diet before pregnancy (H9N\u2010group, \u201ceffectors removal\u201d), followed by pregnancy and lactation, and then offspring were fed high\u2010fat diets after weaning. Offspring livers were analysed by functional studies, as well as next\u2010generation sequencing for gene expression profiles and DNA methylation changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010carbon metabolism that caused DNA hypermethylation and L\u2010carnitine depletion associated with deactivated AMPK signalling and decreased expression of PPAR\u2010\u03b1 and genes for fatty acid oxidation. These changes were not present in H9N offspring. In addition, we identified maternal HF diet\u2010induced genes involved in one\u2010carbon 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrate for the first time that maternal HF diet disrupted the methionine cycle and one\u2010carbon metabolism in offspring livers which further altered lipid homeostasis. CpG islands of specific genes involved in one\u2010carbon metabolism modified by different maternal diets were identified.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14811","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T16:27:09Z","timestamp":1612542429000},"page":"1305-1319","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Maternal high\u2010fat diet disrupted one\u2010carbon metabolism in offspring, contributing to nonalcoholic fatty liver disease"],"prefix":"10.1111","volume":"41","author":[{"given":"Hui","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University College Station TX USA"},{"name":"Tongji Hospital Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiting","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of North Dakota Grand Forks ND USA"},{"name":"Hubei Cancer Hospital Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Biosciences &amp; Technology Texas A&amp;M University Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University College Station TX USA"},{"name":"Department of Statistics Texas A&amp;M University College Station TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University College Station TX USA"},{"name":"Tongji Hospital Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Nutrition Texas A&amp;M University College Station TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan K.","family":"Siwko","sequence":"additional","affiliation":[{"name":"Institute of Biosciences &amp; Technology Texas A&amp;M University Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Tongji Hospital Huazhong University of Science and Technology Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Schalinske","sequence":"additional","affiliation":[{"name":"Department of Food Science and Human Nutrition Iowa State University Ames IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Alpini","sequence":"additional","affiliation":[{"name":"Richard L. 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