why choose us

300×250 Ad Slot

Research Article: Liraglutide reduces lipid accumulation in human orbital fibroblasts in Graves’ orbitopathy

Date Published: 2026-10-07

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 ?-smooth muscle actin (?-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-?–induced myofibroblastic differentiation, or IL-1?–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.

Introduction:
Graves’ orbitopathy (GO), also referred to as thyroid orbitopathy or thyroid eye disease, is the most common orbital disorder and affects approximately 40% of patients with Graves’ disease ( 1 ). Manifestations include conjunctival injection, proptosis, eyelid retraction, restrictive extraocular myopathy, and, in severe cases, vision-threatening optic nerve compression ( 2 ). Despite advances in management, therapeutic options for GO remain limited and are often associated with incomplete responses or…

Read more

300×250 Ad Slot