{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:36:39Z","timestamp":1789000599936,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["14J05809, 15K12346, 26660116, 18K19748"],"award-info":[{"award-number":["14J05809, 15K12346, 26660116, 18K19748"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tojuro Iijima Foundation for Food and Technology","award":["none"],"award-info":[{"award-number":["none"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>l-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in the rat liver. However, the nutritional and physiological functions of Ser synthesis in the liver remain unclear. To clarify the physiological significance of de novo Ser synthesis in the liver, we generated liver hepatocyte-specific Phgdh KO (LKO) mice using an albumin-Cre driver. The LKO mice exhibited a significant gain in body weight compared to Floxed controls at 23 weeks of age and impaired systemic glucose metabolism, which was accompanied by diminished insulin\/IGF signaling. Although LKO mice had no apparent defects in steatosis, the molecular signatures of inflammation and stress responses were evident in the liver of LKO mice. Moreover, LKO mice were more vulnerable to protein starvation than the Floxed mice. These observations demonstrate that Phgdh-dependent de novo Ser synthesis in liver hepatocytes contributes to the maintenance of systemic glucose tolerance, suppression of inflammatory response, and resistance to protein starvation.<\/jats:p>","DOI":"10.3390\/nu13103468","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:03:42Z","timestamp":1632960222000},"page":"3468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Hepatocyte-Specific Phgdh-Deficient Mice Culminate in Mild Obesity, Insulin Resistance, and Enhanced Vulnerability to Protein Starvation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8752-7053","authenticated-orcid":false,"given":"Momoko","family":"Hamano","sequence":"first","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Fukuoka 820-8502, Japan"},{"name":"Laboratory of Functional Genomics and Metabolism, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayoko","family":"Esaki","sequence":"additional","affiliation":[{"name":"Laboratory for Neural Cell Dynamics, RIKEN Center for Brain Science, Wako 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Moriyasu","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokio","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sinya","family":"Mohri","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Laboratory of Molecular Gene Technology, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Innovative Bio-Architecture Center, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Cellular Informatics Laboratory, RIKEN, Wako 351-0198, Japan"},{"name":"Institute for Environmental and Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Chiba 279-0021, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Furuya","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Genomics and Metabolism, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"},{"name":"Innovative Bio-Architecture Center, Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1074\/jbc.C300507200","article-title":"Targeted Disruption of the Mouse 3-Phosphoglycerate Dehydrogenase Gene Causes Severe Neurodevelopmental Defects and Results in Embryonic Lethality","volume":"279","author":"Yoshida","year":"2004","journal-title":"J. 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