{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:51:05Z","timestamp":1785412265122,"version":"3.56.0"},"reference-count":53,"publisher":"Life Science Alliance, LLC","issue":"10","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21gm5010002"],"award-info":[{"award-number":["JP21gm5010002"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP26870926, JP16K21714"],"award-info":[{"award-number":["JP26870926, JP16K21714"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>\n                    \u03b2-Klotho (\u03b2-KL) is indispensable to regulate lipid, glucose, and energy metabolism in adult animals. \u03b2-KL is highly expressed in the yolk sac, but its role in the developmental stages has not been established. We hypothesized that \u03b2-KL is required for metabolic regulation in the embryo and aimed to clarify the role of \u03b2-KL during development. Here, we show that \u03b2-KL regulates feto-maternal cholesterol transport through the yolk sac by mediating FGF 15 signaling, and also that impairment of the \u03b2-KL\u2013FGF15 axis causes fetal growth restriction (FGR). Embryos of\n                    <jats:italic>\u03b2-<\/jats:italic>\n                    <jats:italic>kl<\/jats:italic>\n                    knockout (\n                    <jats:italic>\u03b2-kl<\/jats:italic>\n                    \u2212\/\u2212) mice were morphologically normal but exhibited FGR before placental maturation. The body weight of\n                    <jats:italic>\u03b2-kl<\/jats:italic>\n                    \u2212\/\u2212 mice remained lower after birth. \u03b2-KL deletion reduced cholesterol supply from the maternal blood and led to lipid shortage in the embryos. These phenotypes were similar to those of embryos lacking FGF15, indicating that \u03b2-KL\u2013FGF15 axis is essential for growth and lipid regulation in the embryonic stages. Our findings suggest that lipid abnormalities in early gestation provoke FGR, leading to reduced body size in later life.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202301916","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T11:52:43Z","timestamp":1691581963000},"page":"e202301916","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Feto-maternal cholesterol transport regulated by \u03b2-Klotho\u2013FGF15 axis is essential for fetal growth"],"prefix":"10.26508","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-6604","authenticated-orcid":true,"given":"Kanako","family":"Kobayashi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Aging Science and Medicine, Kyoto University","place":["Graduate School of Medicine, Kyoto, Japan"]},{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Iwasa","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Aging Science and Medicine, Kyoto University","place":["Graduate School of Medicine, Kyoto, Japan"]},{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Azuma-Suzuki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-4474","authenticated-orcid":true,"given":"Takeshi","family":"Kawauchi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Aging Science and Medicine, Kyoto University","place":["Graduate School of Medicine, Kyoto, Japan"]},{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan"},{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Adaptive and Maladaptive Responses in Health and Disease, Kyoto University","place":["Graduate School of Medicine, Kyoto, Japan"]},{"name":"Department of Physiology, Keio University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-2181","authenticated-orcid":true,"given":"Yo-ichi","family":"Nabeshima","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02kpeqv85","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Aging Science and Medicine, Kyoto University","place":["Graduate School of Medicine, Kyoto, Japan"]},{"name":"Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"12380","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"2023082309494476000_6.10.e202301916.1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2007.01809.x"},{"key":"2023082309494476000_6.10.e202301916.2","first-page":"183","article-title":"Distinct roles for visceral endoderm during embryonic mouse development","volume":"43","author":"Bielinska","year":"1999","journal-title":"Int J Dev Biol"},{"key":"2023082309494476000_6.10.e202301916.3","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-017-0442-y"},{"key":"2023082309494476000_6.10.e202301916.4","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3249"},{"key":"2023082309494476000_6.10.e202301916.5","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.071480"},{"key":"2023082309494476000_6.10.e202301916.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.12.024"},{"key":"2023082309494476000_6.10.e202301916.7","doi-asserted-by":"publisher","DOI":"10.1113\/JP271745"},{"key":"2023082309494476000_6.10.e202301916.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1702560114"},{"key":"2023082309494476000_6.10.e202301916.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.12.004"},{"key":"2023082309494476000_6.10.e202301916.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.7985020"},{"key":"2023082309494476000_6.10.e202301916.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.08.002"},{"key":"2023082309494476000_6.10.e202301916.12","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20071512"},{"key":"2023082309494476000_6.10.e202301916.13","doi-asserted-by":"publisher","DOI":"10.1002\/ajhb.20995"},{"key":"2023082309494476000_6.10.e202301916.14","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-2275(20)37621-5"},{"key":"2023082309494476000_6.10.e202301916.15","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1307-8_22"},{"key":"2023082309494476000_6.10.e202301916.16","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"2023082309494476000_6.10.e202301916.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00717-1"},{"key":"2023082309494476000_6.10.e202301916.18","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90046-5"},{"key":"2023082309494476000_6.10.e202301916.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47964-1"},{"key":"2023082309494476000_6.10.e202301916.20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111872"},{"key":"2023082309494476000_6.10.e202301916.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.09.001"},{"key":"2023082309494476000_6.10.e202301916.22","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00439-1"},{"key":"2023082309494476000_6.10.e202301916.23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23076"},{"key":"2023082309494476000_6.10.e202301916.24","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2289"},{"key":"2023082309494476000_6.10.e202301916.25","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00804-9"},{"key":"2023082309494476000_6.10.e202301916.26","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"2023082309494476000_6.10.e202301916.27","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-274449"},{"key":"2023082309494476000_6.10.e202301916.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.09.005"},{"key":"2023082309494476000_6.10.e202301916.29","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.761"},{"key":"2023082309494476000_6.10.e202301916.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2006.01731.x"},{"key":"2023082309494476000_6.10.e202301916.31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.280.2.e334"},{"key":"2023082309494476000_6.10.e202301916.32","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.17.3221"},{"key":"2023082309494476000_6.10.e202301916.33","unstructured":"Nagy A , Gertsenstein M , Vintersten K , Behringer R (2002) Manipulating the Mouse Embryo: A Laboratory Manual, Third edition. New York, NY: Cold Spring Harbor Laboratory Press."},{"key":"2023082309494476000_6.10.e202301916.34","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(84)90484-6"},{"key":"2023082309494476000_6.10.e202301916.35","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3250"},{"key":"2023082309494476000_6.10.e202301916.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2014.10.002"},{"key":"2023082309494476000_6.10.e202301916.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8686"},{"key":"2023082309494476000_6.10.e202301916.38","doi-asserted-by":"publisher","DOI":"10.1038\/35080570"},{"key":"2023082309494476000_6.10.e202301916.39","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"2023082309494476000_6.10.e202301916.40","doi-asserted-by":"publisher","DOI":"10.3390\/nu10060760"},{"key":"2023082309494476000_6.10.e202301916.41","doi-asserted-by":"publisher","DOI":"10.1159\/000464302"},{"key":"2023082309494476000_6.10.e202301916.42","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0395"},{"key":"2023082309494476000_6.10.e202301916.43","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91809"},{"key":"2023082309494476000_6.10.e202301916.44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00182.2018"},{"key":"2023082309494476000_6.10.e202301916.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913986107"},{"key":"2023082309494476000_6.10.e202301916.46","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6030"},{"key":"2023082309494476000_6.10.e202301916.47","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00951"},{"key":"2023082309494476000_6.10.e202301916.48","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/82.6.1155"},{"key":"2023082309494476000_6.10.e202301916.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2004.02.003"},{"key":"2023082309494476000_6.10.e202301916.50","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500096-JLR200"},{"key":"2023082309494476000_6.10.e202301916.51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411771200"},{"key":"2023082309494476000_6.10.e202301916.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03038-w"},{"key":"2023082309494476000_6.10.e202301916.53","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20705"}],"container-title":["Life Science Alliance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.26508\/lsa.202301916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T09:08:00Z","timestamp":1704877680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.life-science-alliance.org\/lookup\/doi\/10.26508\/lsa.202301916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":53,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,8,4]]},"published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.26508\/lsa.202301916"],"URL":"https:\/\/doi.org\/10.26508\/lsa.202301916","relation":{},"ISSN":["2575-1077"],"issn-type":[{"value":"2575-1077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]}}}