Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, China.
College of Fisheries and Life Science, Dalian Ocean University, Dalian, Liaoning, China.
FASEB J. 2024 Jun 15;38(11):e23717. doi: 10.1096/fj.202400575RR.
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 (VO), carbon dioxide production (VCO), 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.
硒蛋白 I（Selenoi）在肝脏中高度表达，作为一种磷脂酰乙醇胺（PE）合酶，在脂质代谢中发挥关键作用。然而，Selenoi 在肝脏中的确切功能仍不清楚。在这项研究中，我们在高脂肪饮食的条件下生成了肝细胞特异性的 Selenoi 条件性敲除（cKO）小鼠，以确定 Selenoi 的生理功能。cKO 组的体重显著增加，白色脂肪组织（WAT）和肝脏中的脂肪积累分别增加了 15.6%和 13.7%。cKO 小鼠肝脏中脂解相关蛋白（p-Hsl）下调，脂肪生成相关蛋白（Fasn）上调。cKO 组的耗氧量（VO）、二氧化碳产生量（VCO）和能量消耗也降低（p<.05）。此外，cKO 小鼠肝脏中的类固醇激素合成途径的各种代谢物也受到影响。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 Selenoi cKO 与生化和分子反应联系起来的核心机制。总之，我们揭示了 Selenoi 抑制体脂肪积累和肝脂肪变性并增加能量消耗；该蛋白也可被视为治疗此类相关疾病的潜在靶点。
