Abstract：
Selenoprotein I (Selenoi) is highly expressed in liver and plays a key role in lipid metabolism as a phosphatidylethanolamine (PE) synthase. However, the precise function of Selenoi in the liver remains elusive. In the study, we generated hepatocyte-specific Selenoi conditional knockout (cKO) mice on a high-fat diet to identify the physiological function of Selenoi. The cKO group exhibited a significant increase in body weight, with a 15.6% and 13.7% increase in fat accumulation in white adipose tissue (WAT) and the liver, respectively. Downregulation of the lipolysis-related protein (p-Hsl) and upregulation of the adipogenesis-related protein (Fasn) were observed in the liver of cKO mice. The cKO group also showed decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (p < .05). Moreover, various metabolites of the steroid hormone synthesis pathway were affected in the liver of cKO mice. A potential cascade of Selenoi-phosphatidylethanolamine-steroid hormone synthesis might serve as a core mechanism that links hepatocyte-specific Selenoi cKO to biochemical and molecular reactions. In conclusion, we revealed that Selenoi inhibits body fat accumulation and hepatic steatosis and elevates energy consumption; this protein could also be considered a therapeutic target for such related diseases.
摘要：
硒蛋白I（Selenoi）在肝脏中高度表达，并作为磷脂酰乙醇胺（PE）合酶在脂质代谢中起关键作用。然而,Selenoi在肝脏中的确切功能仍然难以捉摸。在研究中,我们在高脂饮食中产生了肝细胞特异性Selenoi条件敲除（cKO）小鼠，以鉴定Selenoi的生理功能。cKO组显示体重显著增加，白色脂肪组织（WAT）和肝脏中的脂肪积累增加15.6%和13.7%，分别。在cKO小鼠的肝脏中观察到脂解相关蛋白（p-Hsl）的下调和脂肪生成相关蛋白（Fasn）的上调。cKO组也显示出减少的耗氧量（VO2），二氧化碳产量(VCO2)，和能量消耗（p<0.05）。此外，在cKO小鼠的肝脏中，类固醇激素合成途径的各种代谢产物受到影响。Selenoi-磷脂酰乙醇胺-类固醇激素合成的潜在级联反应可能是将肝细胞特异性SelenoicKO与生化和分子反应联系起来的核心机制。总之,我们发现Selenoi抑制体内脂肪堆积和肝脏脂肪变性并增加能量消耗;该蛋白也可被认为是此类相关疾病的治疗靶点.
