AUTHOR=Li Hong , Yuan Yifei , Zhang Yali , Zhang Xia , Gao Long , Xu Rongjuan TITLE=Icariin Inhibits AMPK-Dependent Autophagy and Adipogenesis in Adipocytes In vitro and in a Model of Graves' Orbitopathy In vivo JOURNAL=Frontiers in Physiology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.00045 DOI=10.3389/fphys.2017.00045 ISSN=1664-042X ABSTRACT=

Graves' orbitopathy (GO), an extrathyroidal manifestation of Graves' disease, is an inflammatory autoimmune disorder of the orbit that involves the differentiation of precursor cells into mature adipocytes and retro-orbital adipose tissue accumulation. Here, we examined the involvement of autophagy in adipogenesis and explored the effects of icariin, a flavonoid isolated from the genus Epimedium with a wide range of biological and pharmacological effects, on autophagy and adipogenesis in 3T3-L1 preadipocytes and in a mouse model of GO. Microscopic examination of autophagosome formation and lipid droplet accumulation by Oil Red O staining, and western blot assessment of autophagic markers in the presence of the autophagy inhibitors Asn and 3-MA showed that autophagy is essential for adipogenesis. Icariin inhibited the differentiation of preadipocytes into mature adipocytes by suppressing autophagy, and these effects were mediated by the inhibition of AMPK/mTOR pathway activation. In a mouse model of thyroid stimulating hormone receptor induced GO, icariin reduced orbital muscle adipose tissue expansion and lipid droplet accumulation by inhibiting AMPK/mTOR mediated autophagy. Collectively, these results reveal a potential mechanism underlying the protective effects of icariin against autophagy induced adipogenesis and suggest that icariin could be developed as a new therapeutic candidate for the prevention and treatment of GO.