{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:15:26Z","timestamp":1792498526418,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2016YFD0501200"],"award-info":[{"award-number":["2016YFD0501200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Undernutrition accelerates body fat mobilization to alleviate negative energy balance, which disrupts homeostasis of lipid metabolism in maternal liver. However, little is known about its effect on fetal metabolism and development. Here, a sheep model was used to explore whether maternal undernutrition induces fetal lipid metabolism disorder and further inhibits fetal hepatic development. Twenty pregnant ewes were either fed normally or restricted to 30% level for 15 d, after which fetal hepatic samples were collected to conduct transcriptome, metabolome, histomorphology, and biochemical analysis. Results showed that maternal undernutrition altered the general transcriptome profile and metabolic mode in fetal liver. Fatty acid oxidation and ketogenesis were enhanced in fetal livers of undernourished ewes, which might be promoted by the activated peroxisome proliferator\u2010activated receptor \u03b1 signaling pathway, whereas cholesterol, steroid, and fatty acid synthesis were repressed. Maternal undernutrition increased triglyceride synthesis, decreased triglyceride degradation, and inhibited phospholipid degradation and synthesis in fetal liver. In addition, our data revealed that maternal undernutrition extremely inhibited DNA replication, cell cycle progression, and antiapoptosis and broke the balance between cell proliferation and apoptosis in fetal liver, indicating that maternal undernutrition affects the growth and development of fetal liver. Generally, these findings provide evidence that maternal undernutrition during pregnancy disturbs fetal lipid metabolism and inhibits fetal hepatic development in sheep, which greatly contribute to the further study of fetal metabolism and development in human beings.\u2014Xue, Y., Guo, C., Hu, F., Zhu, W., Mao, S. Maternal undernutrition induces fetal hepatic lipid metabolism disorder and affects the development of fetal liver in a sheep model. FASEB J. 33, 9990\u201310004 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900406r","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T17:44:53Z","timestamp":1559756693000},"page":"9990-10004","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Maternal undernutrition induces fetal hepatic lipid metabolism disorder and affects the development of fetal liver in a sheep model"],"prefix":"10.1096","volume":"33","author":[{"given":"Yanfeng","family":"Xue","sequence":"first","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changzheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyong","family":"Mao","sequence":"additional","affiliation":[{"name":"Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health College of Animal Science and Technology Nanjing Agricultural University  Nanjing China"},{"name":"National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal Science Nanjing Agricultural University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2009.07.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61693-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/72.1.212S"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2006-156"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxq001"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1441"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/71.5.1295s"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/jn\/99.1.61","article-title":"Effect of protein deprivation of swine during all or part of gestation on birth weight, postnatal growth rate and nucleic acid content of brain and muscle of progeny","volume":"99","author":"Pond W. G.","year":"1969","journal-title":"J. Nutr."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2007-0624"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3016.2012.01291.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0007-1935(17)30436-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.029645"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agu108"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2015.03.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1939-165X.2008.00076.x","article-title":"Metabolic profiles in goat does in late pregnancy with and without subclinical pregnancy toxemia","volume":"37","author":"Ismail Z. A.","year":"2008","journal-title":"Vet. Clin. Pathol."},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1590\/S0102-09352009000200004","article-title":"Histological changes of the liver and metabolic correlates in ewes with pregnancy toxemia","volume":"61","author":"Cal L.","year":"2009","journal-title":"Arq. Bras. Med. Vet. Zootec."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/00480169.2014.971083"},{"key":"e_1_2_9_19_1","first-page":"470","article-title":"Histopathological analysis of liver during pregnancy toxemia in small\u2010tailed han sheep","volume":"15","author":"Wang M.","year":"2014","journal-title":"Agrie. Sci. Technol."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo8040085"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1751731118002136"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp356"},{"key":"e_1_2_9_24_1","first-page":"361","article-title":"Gephi: an open source software for exploring and manipulating networks","volume":"2","author":"Bastian M.","year":"2009","journal-title":"Am. J. Sociol."},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.9.2169"},{"key":"e_1_2_9_26_1","first-page":"220","volume-title":"Energy and protein requirements: WHO Technical Report series No. 724","author":"World Health Organization, Food and Agricultural Organization, United Nations University","year":"1985"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.49.070180.002143"},{"key":"e_1_2_9_28_1","first-page":"137","article-title":"Physiological aspects of the regulation of ketogenesis","volume":"43","author":"Williamson D. H.","year":"1978","journal-title":"Biochem. Soc. Symp."},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"18767","DOI":"10.1016\/S0021-9258(17)32234-2","article-title":"Peroxisome proliferator\u2010activated receptor mediates induction of the mitochondrial 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010CoA synthase gene by fatty acids","volume":"269","author":"Rodr\u00edguez J. C.","year":"1994","journal-title":"J. Biol. Chem."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1064"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1080353"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1621\/nrs.08002"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.21.1.193"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1385\/ENDO:19:1:43"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"557","DOI":"10.17221\/8598-CJAS","article-title":"Effects of feed intake restriction during late pregnancy on maternal metabolic changes and fetal development in ewes","volume":"60","author":"Zhang C. Z.","year":"2015","journal-title":"Czech J. Anim. Sci."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh083"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3197"},{"key":"e_1_2_9_38_1","first-page":"4611","article-title":"Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines","volume":"58","author":"Pizer E. S.","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0301fje"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059108"},{"key":"e_1_2_9_41_1","first-page":"1437","article-title":"Prolonged exposure to free fatty acids has cytostatic and pro\u2010apoptotic effects on human pancreatic islets: evidence that beta\u2010cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl\u20102 regulated","volume":"51","author":"Lupi R.","year":"2002","journal-title":"Di abetes"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.4.991"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/20.5.757"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.11.1359"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2002.02822.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1159\/000091507"},{"key":"e_1_2_9_47_1","volume-title":"Biochemistry of Lipids, Lipoproteins, and Membranes","author":"Vance D. E.","year":"1991"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2012.08.019"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301982200"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900406R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201900406R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900406R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:29:40Z","timestamp":1761672580000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201900406R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,5]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1096\/fj.201900406R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201900406r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,5]]},"assertion":[{"value":"2019-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}