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Metformin has been suggested as a potential treatment for body weight reduction and nonalcoholic fatty liver disease, but its reprogramming effect on offspring is undetermined. This study assesses the effects of maternal metformin treatment on hepatic steatosis in offspring caused by maternal HF diet. Female rats were fed either a control or an HF diet before conception, with or without metformin treatment during gestation, and placenta and fetal liver tissues were collected. In another experiment, the offspring were fed a control diet until 120 d (adult stage). Metformin treatment during pregnancy ameliorates placental oxidative stress and enhances placental glucose transporter 1 (GLUT1), GLUT3, and GLUT4 expression levels through 5\u2019 adenosine monophosphate-activated protein kinase (AMPK) activation. Maternal metformin treatment was shown to reprogram maternal HF diet-induced changes in offspring fatty liver with the effects observed in adulthood as well. Further validation is required to develop maternal metformin therapy for clinical applications.<\/jats:p>","DOI":"10.3390\/ijms232214239","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:29:50Z","timestamp":1668742190000},"page":"14239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Maternal Metformin Treatment Reprograms Maternal High-Fat Diet-Induced Hepatic Steatosis in Offspring Associated with Placental Glucose Transporter Modifications"],"prefix":"10.3390","volume":"23","author":[{"given":"Chien-Fu","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mao-Meng","family":"Tiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7403-288X","authenticated-orcid":false,"given":"Li-Tung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiunn-Ming","family":"Sheen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-6407","authenticated-orcid":false,"given":"You-Lin","family":"Tain","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-528X","authenticated-orcid":false,"given":"Chien-Ning","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8302-1477","authenticated-orcid":false,"given":"Ching-Chou","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1242-8760","authenticated-orcid":false,"given":"Hong-Ren","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/S0140-6736(14)60460-8","article-title":"Global, regional, and national prevalence of overweight and obesity in children and adults during 1980\u20132013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Ng","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1017\/S0954422410000168","article-title":"High-fat diet-induced obesity in animal models","volume":"23","author":"Hariri","year":"2010","journal-title":"Nutr. 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