Kipp Zachary A, Martinez Genesee J, Bates Evelyn A, Maharramov Agil B, Flight Robert M, Moseley Hunter N B, Morris Andrew J, Stec David E, Hinds Terry D
Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA.
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40508, USA.
Metabolites. 2023 Feb 1;13(2):215. doi: 10.3390/metabo13020215.
Studies have indicated that increasing plasma bilirubin levels might be useful for preventing and treating hepatic lipid accumulation that occurs with metabolic diseases such as obesity and diabetes. We have previously demonstrated that mice with hyperbilirubinemia had significantly less lipid accumulation in a diet-induced non-alcoholic fatty liver disease (NAFLD) model. However, bilirubin's effects on individual lipid species are currently unknown. Therefore, we used liquid chromatography-mass spectroscopy (LC-MS) to determine the hepatic lipid composition of obese mice with NAFLD treated with bilirubin nanoparticles or vehicle control. We placed the mice on a high-fat diet (HFD) for 24 weeks and then treated them with bilirubin nanoparticles or vehicle control for 4 weeks while maintaining the HFD. Bilirubin nanoparticles suppressed hepatic fat content overall. After analyzing the lipidomics data, we determined that bilirubin inhibited the accumulation of ceramides in the liver. The bilirubin nanoparticles significantly lowered the hepatic expression of two essential enzymes that regulate ceramide production, and . Our results demonstrate that the bilirubin nanoparticles improve hepatic fat content by reducing ceramide production, remodeling the liver fat content, and improving overall metabolic health.
研究表明，提高血浆胆红素水平可能有助于预防和治疗肥胖症和糖尿病等代谢性疾病伴发的肝脏脂质蓄积。我们之前已经证明，在饮食诱导的非酒精性脂肪性肝病（NAFLD）模型中，高胆红素血症小鼠的脂质蓄积显著减少。然而，胆红素对单个脂质种类的影响目前尚不清楚。因此，我们使用液相色谱-质谱联用（LC-MS）来确定用胆红素纳米颗粒或载体对照处理的NAFLD肥胖小鼠的肝脏脂质组成。我们将小鼠置于高脂饮食（HFD）24周，然后在用胆红素纳米颗粒或载体对照处理4周的同时维持HFD。胆红素纳米颗粒总体上抑制了肝脏脂肪含量。在分析脂质组学数据后，我们确定胆红素抑制了肝脏中神经酰胺的蓄积。胆红素纳米颗粒显著降低了两种调节神经酰胺生成的关键酶的肝脏表达，以及。我们的结果表明，胆红素纳米颗粒通过减少神经酰胺生成、重塑肝脏脂肪含量和改善整体代谢健康来改善肝脏脂肪含量。
