{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:14:17Z","timestamp":1783617257100,"version":"3.55.0"},"reference-count":128,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pregnancy is a physiological state of transient, reversible insulin resistance accompanied by major adaptations in glucose and lipid metabolism. Although placental hormones are key drivers of gestational insulin resistance, the mechanisms underlying the rapid restoration of insulin sensitivity after delivery remain incompletely understood. This review proposes a conceptual framework in which fibroblast growth factor 21 (FGF21) and sex hormone-binding globulin (SHBG) are considered as complementary hepatic signals potentially involved in maternal metabolic adaptation. During late pregnancy, FGF21 may function as a metabolic stress-response factor associated with fatty acid oxidation, lipid handling, and mitochondrial adaptation through AMPK\u2013PPAR\u03b1-related pathways. Reduced SHBG, in contrast, may reflect hepatic insulin resistance and altered hepatic metabolic regulation. After delivery, changes in FGF21 and SHBG levels may be associated with recovery of hepatic metabolic homeostasis and insulin sensitivity, while persistent adaptive FGF21 signaling facilitate metabolic reprogramming may contribute to ongoing metabolic adaptation. Postpartum metabolic recovery may therefore represent an active and dynamic process rather than a purely passive consequence of placental hormone withdrawal. Disruption of FGF21- and SHBG-mediated pathways may contribute to persistent insulin resistance and increased cardiometabolic risk after gestational diabetes. Understanding hepatokine-mediated regulation of maternal metabolic flexibility may provide further insight into postpartum metabolic recovery and may support future development of risk stratification strategies, biomarker-based approaches, and preventive interventions aimed at reducing the risk of type 2 diabetes after pregnancy.<\/jats:p>","DOI":"10.3390\/biom16070998","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"998","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FGF21 and SHBG as Putative Hepatic Axes in Maternal Metabolic Adaptation: A Hypothetical Framework for Postpartum Insulin Sensitivity Restoration"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6077-4940","authenticated-orcid":false,"given":"Kornelia","family":"Purc-Bandurko","sequence":"first","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Trojnar","sequence":"additional","affiliation":[{"name":"Student\u2019s Scientific Association at the Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Masiarz","sequence":"additional","affiliation":[{"name":"Student\u2019s Scientific Association at the Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Bandurko","sequence":"additional","affiliation":[{"name":"Department of Urology, Center of Oncology of the Lublin Region, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-0409","authenticated-orcid":false,"given":"\u017baneta","family":"Kimber-Trojnar","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017cena","family":"Leszczy\u0144ska-Gorzelak","sequence":"additional","affiliation":[{"name":"Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Plows, J.F., Stanley, J.L., Baker, P.N., Reynolds, C.M., and Vickers, M.H. 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