LSD1 induces H3K9 demethylation to promote adipogenesis in Thyroid associated ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease, multiple factors including genetic and immune factors, contribute to TAO progression, thus there is no available drugs targeting TAO. Here, we investigated the underlying mechanism of adipogenesis in TAO from an epigenetic point, we found lysine specific demethylase (LSD1) was highly expressed in TAO compared with non-TAO, and knocking down LSD1 led to decreased expression of adipocyte markers and inflammatory genes. Mechanically, LSD1 removed the H3K9me2 mark on the promoter of adipocyte genes, activating their expression. Finally, pargyline, an inhibitor of LSD1, inhibited adpogenesis in a dose-dependent manner. Taken together, our study revealed a novel mechanism of adipocyte differentiation during TAO progression, and demonstrated LSD1 is a potential anti-adipogenesis target in TAO.