{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:52:05Z","timestamp":1791348725762,"version":"4.3.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Graves\u2019 orbitopathy (GO) is characterized by proliferation and differentiation of orbital fibroblasts. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic disorders and have been reported to modulate cell proliferation and differentiation. The present study aimed to examine the effects of GLP-1RAs on key fibroblast-mediated pathogenic processes relevant to GO using human orbital fibroblasts. Orbital fibroblasts were isolated from patients with GO and non-GO controls. Cells were treated with the GLP-1RAs liraglutide (100 nM) or semaglutide (200 nM). Fibroblast proliferation was assessed by nuclear counting, lipid accumulation was evaluated by Oil Red O staining of oil droplets, and myofibroblastic differentiation was assessed by \u03b1-smooth muscle actin (\u03b1-SMA) immunostaining. Hyaluronan production was measured by ELISA.\n                    <jats:italic>GLP1R<\/jats:italic>\n                    mRNA expression was examined using reverse transcription quantitative PCR. Among the outcomes assessed, liraglutide significantly reduced lipid accumulation in GO-derived orbital fibroblasts, whereas semaglutide showed a nonsignificant trend in the same direction. Neither liraglutide nor semaglutide significantly altered lipid accumulation in non-GO fibroblasts. Importantly, neither GLP-1RA increased fibroblast proliferation, TGF-\u03b2\u2013induced myofibroblastic differentiation, or IL-1\u03b2\u2013induced hyaluronan production in GO or non-GO fibroblasts under the tested conditions.\n                    <jats:italic>GLP1R<\/jats:italic>\n                    mRNA was not reliably detected, and the underlying mechanism remains uncertain. Taken together, this\n                    <jats:italic>in vitro<\/jats:italic>\n                    study showed a significant reduction in lipid accumulation following liraglutide treatment in GO-derived orbital fibroblasts, while semaglutide showed a trend in the same direction that did not reach statistical significance. Neither agent enhanced fibroblast proliferation, myofibroblastic differentiation, or hyaluronan production under the tested conditions. These findings suggest a potentially favorable biological profile of liraglutide in GO and warrant further studies to clarify the underlying mechanisms and assess its clinical relevance, particularly in patients with metabolic comorbidities.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1914378","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:46:36Z","timestamp":1791348396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves\u2019 orbitopathy"],"prefix":"10.3389","volume":"17","author":[{"given":"Chih-Wei","family":"Shih","sequence":"first","affiliation":[{"name":"Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine","place":["Taipei, Taiwan"]},{"name":"Department of Ophthalmology, Zhongxing Branch, Taipei City Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Ophthalmology, Good Will Clinic","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyang-Rong","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Internal Medicine, National Taiwan University College of Medicine","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hsuan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Hung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Lang","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Taiwan University Hospital","place":["Taipei, Taiwan"]},{"name":"Department of Ophthalmology, National Taiwan University College of Medicine","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-An","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital","place":["Taipei, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hou-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, National Taiwan 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