title: Icariin Inhibits AMPK-Dependent Autophagy and Adipogenesis in AdipocytesIn vitroand in a Model of Graves' OrbitopathyIn vivo.
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 genusEpimediumwith 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.
authors.affiliation: Department of Endocrinology, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University Shanghai, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Spleen and Stomach Disease, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Long
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Longhua Hospital Shanghai University of Traditional Chinese Medicine Shanghai, China.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Xu
keywords: Graves' orbitopathy; adipogenesis; autophagy; icariin; thyroid stimulating hormone receptor