Max Planck Institute for Biology of Ageing, Cologne, Germany.
Exp Dermatol. 2012 Sep;21(9):712-3. doi: 10.1111/j.1600-0625.2012.01558.x.
Ulcerative dermatitis (UD) is a severe inflammatory skin disorder with an unknown aetiology. Recently, insulin receptor substrate 1 KO mice were shown to be fully resistant to UD. In this study, we showed that high-fat diet (HFD) feeding significantly increased incidence of UD in wild type (WT) C57BL/6 mice, as did lithium-mediated inhibition of GSK3-β, which is a key negative regulator of IRS1. In contrast to WT mice, resistance to UD was fully preserved in HFD-fed Irs1-KO mice. Our results identify IRS1 as a key determinant of UD pathogenesis and establish a direct link between diet composition, obesity-induced inflammation and chronic ulceration.
溃疡性皮炎（UD）是一种严重的炎症性皮肤疾病，其病因不明。最近，胰岛素受体底物 1 KO 小鼠被证明对 UD 完全具有抗性。在这项研究中，我们发现高脂肪饮食（HFD）喂养显著增加了野生型（WT）C57BL/6 小鼠 UD 的发病率，锂介导的 GSK3-β抑制也是 IRS1 的关键负调节剂。与 WT 小鼠相比，HFD 喂养的 Irs1-KO 小鼠对 UD 的抗性得到完全保留。我们的研究结果确定 IRS1 是 UD 发病机制的关键决定因素，并在饮食成分、肥胖引起的炎症和慢性溃疡之间建立了直接联系。
