Liraglutide significantly reduces lipid accumulation in human orbital fibroblasts from Graves' orbitopathy

Graves' orbitopathy (GO), also known as thyroid eye disease, is an autoimmune condition characterized by the abnormal proliferation and differentiation of orbital fibroblasts. These fibroblasts accumulate lipids and produce excessive hyaluronan, leading to tissue expansion, inflammation, and eye bulging. Current treatments often involve corticosteroids or surgery, which have significant side effects or are invasive. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), like liraglutide, are widely used for metabolic disorders and have shown potential in modulating cell growth and differentiation, making them interesting candidates for targeting the underlying fibroblast pathology in GO. This study investigates their direct effects on GO fibroblasts.

Researchers conducted an in vitro study using human orbital fibroblasts isolated from Graves' orbitopathy (GO) patients and non-GO controls. Cells were treated with liraglutide (100 nM) or semaglutide (200 nM). Fibroblast proliferation was quantified via nuclear counting. Lipid accumulation was assessed using Oil Red O staining. Myofibroblastic differentiation was evaluated by α-smooth muscle actin (α-SMA) immunostaining. Hyaluronan production was measured using ELISA, and GLP1R mRNA expression was examined via reverse transcription quantitative PCR.