Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves' orbitopathy.
8 affiliations
- 1Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- 2Department of Ophthalmology, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan.
- 3Department of Ophthalmology, Good Will Clinic, Taipei, Taiwan.
- 4Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- 5Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- 6Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
- 7Department of Ophthalmology, National Taiwan University College of Medicine, Taipei, Taiwan.
- 8Department of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.
Abstract
Graves' 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 α-smooth muscle actin (α-SMA) immunostaining. Hyaluronan production was measured by ELISA. GLP1R 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-β-induced myofibroblastic differentiation, or IL-1β-induced hyaluronan production in GO or non-GO fibroblasts under the tested conditions. GLP1R mRNA was not reliably detected, and the underlying mechanism remains uncertain. Taken together, this in vitro 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.
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BibTeX
@article{shih2026liraglutide,
title = {{Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves' orbitopathy.}},
author = {Chih-Wei Shih and Shyang-Rong Shih and Yi-Hsuan Wei and Chia-Hung Lin and Shu-Lang Liao and Ting-An Chou and I Chu and Hou-Jen Chen and Neng-Li Liao and Feng-Chiao Tsai},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1914378},
url = {https://europepmc.org/article/MED/42908606},
note = {CC BY},
}
RIS
TY - JOUR
TI - Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves' orbitopathy.
AU - Chih-Wei Shih
AU - Shyang-Rong Shih
AU - Yi-Hsuan Wei
AU - Chia-Hung Lin
AU - Shu-Lang Liao
AU - Ting-An Chou
AU - I Chu
AU - Hou-Jen Chen
AU - Neng-Li Liao
AU - Feng-Chiao Tsai
PY - 2026
DA - 2026/10/07
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1914378
UR - https://europepmc.org/article/MED/42908606
AB - Graves' 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 α-smooth muscle actin (α-SMA) immunostaining. Hyaluronan production was measured by ELISA. GLP1R 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-β-induced myofibroblastic differentiation, or IL-1β-induced hyaluronan production in GO or non-GO fibroblasts under the tested conditions. GLP1R mRNA was not reliably detected, and the underlying mechanism remains uncertain. Taken together, this in vitro 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.
SN - 1664-2392
ER -