{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:56:59Z","timestamp":1787590619212,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100030680","name":"Fu Jen Catholic University Hospital","doi-asserted-by":"publisher","award":["PL\u2010201908010\u2010V"],"award-info":[{"award-number":["PL\u2010201908010\u2010V"]}],"id":[{"id":"10.13039\/100030680","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Angiopoietin\u2010like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non\u2010pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A\u2010sub\u2010E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose\u2013response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone\u2010variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin\u2010mediated glucose uptake through the epidermal growth factor receptor (EGFR)\/extracellular signal\u2010regulated kinases 1\/2 (ERK 1\/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI\n                    <jats:sub>0,120<\/jats:sub>\n                    in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.\n                  <\/jats:p>","DOI":"10.1002\/biof.2076","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T21:08:51Z","timestamp":1715980131000},"page":"1176-1191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Angiopoietin\u2010like protein 4 induces growth hormone variant secretion and aggravates insulin resistance during pregnancy, linking obesity to gestational diabetes mellitus"],"prefix":"10.1002","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7673-3567","authenticated-orcid":false,"given":"Chun\u2010Heng","family":"Kuo","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University  Taipei Taiwan"},{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University  New Taipei City Taiwan"},{"name":"Department of Internal Medicine Fu Jen Catholic University Hospital, Fu Jen Catholic University  New Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu\u2010Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology College of Medicine, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsien\u2010Chia","family":"Juan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9016-4376","authenticated-orcid":false,"given":"Szu\u2010Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Taipei City Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Hua","family":"Kuo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Medicine, National Taiwan University  Taipei Taiwan"},{"name":"The Metabolomics Core Laboratory Centers of Genomic and Precision Medicine, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Chun","family":"Kuo","sequence":"additional","affiliation":[{"name":"The Metabolomics Core Laboratory Centers of Genomic and Precision Medicine, National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0753-2793","authenticated-orcid":false,"given":"Shin\u2010Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology National Taiwan University Hospital  Taipei 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