Objective Thyroid hormones have been associated with a hepatic lipid lowering effect and thyroid function has been shown to play a substantial role in development of non-alcoholic fatty liver disease. Hepatic lipid droplets differ in the number, size and molecular properties depending on metabolic state or pathological condition. However, in how far thyroid hormone deficiency affects hepatic lipid droplet morphology and molecular properties is still poorly understood. Therefore, we performed a study in mice using a lithogenic diet model of steatohepatitis and modulated the thyroid hormone status. Methods Male and female three months old C57BL/6 mice were divided into a euthyroid (control), a lithogenic (litho) and a lithogenic+thyroid hormone deficient (litho+hypo) group and treated for six weeks. Hepatic transmission electron microscopy and gene expression analysis of lipid-droplet associated proteins were performed. Results Increased mean diameters of hepatic lipid droplets and a shift towards raised electron-density in lipid droplets was observed under thyroid hormone deficiency. Furthermore thyroid hormone deficiency altered hepatic expression of genes involved in lipophagy and triacylglycerol mobilization. Interestingly, while the impact of thyroid hormone deficiency on lipid droplet morphology seems to be sex-independent, hepatic lipid droplet-associated gene expression differed significantly between both sexes. Conclusion This study demonstrates that thyroid hormone deficiency alters hepatic lipid droplet morphology and hepatic gene expression of lipid droplet-associated proteins in a lithogenic diet mouse model of steatohepatitis.

中文翻译：

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甲状腺激素缺乏改变了生石饮食补充小鼠的肝脂滴形态和分子特性

目的 甲状腺激素与肝脏降脂作用有关，甲状腺功能已被证明在非酒精性脂肪肝的发展中起重要作用。肝脏脂滴的数量、大小和分子特性因代谢状态或病理状况而异。然而，甲状腺激素缺乏对肝脏脂滴形态和分子特性的影响程度仍然知之甚少。因此，我们使用脂肪性肝炎的致石饮食模型在小鼠中进行了一项研究，并调节了甲状腺激素状态。方法将雄性和雌性3个月大的C57BL/6小鼠分为甲状腺功能正常组（对照）、生石组（litho）和生石+甲状腺激素缺乏组（litho+hypo），治疗6周。进行了脂滴相关蛋白的肝透射电子显微镜和基因表达分析。结果甲状腺激素缺乏时肝脏脂滴平均直径增加，脂滴电子密度增加。此外，甲状腺激素缺乏改变了参与脂肪吞噬和三酰基甘油动员的基因的肝脏表达。有趣的是，虽然甲状腺激素缺乏对脂滴形态的影响似乎与性别无关，但与肝脂滴相关的基因表达在两性之间存在显着差异。结论 本研究表明，在脂肪性肝炎的致石饮食小鼠模型中，甲状腺激素缺乏会改变肝脏脂滴形态和脂滴相关蛋白的肝脏基因表达。