Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, 75006 Paris, France.
Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Diabetes Department, Hospital Pitié-Salpêtrière, 75013 Paris, France.
Cell Rep Med. 2020 Dec 22;1(9):100154. doi: 10.1016/j.xcrm.2020.100154.
Plasma dihydroceramides are predictors of type 2 diabetes and related to metabolic dysfunctions, but the underlying mechanisms are not characterized. We compare the relationships between plasma dihydroceramides and biochemical and hepatic parameters in two cohorts of diabetic patients. Hepatic steatosis, steatohepatitis, and fibrosis are assessed by their plasma biomarkers. Plasma lipoprotein sphingolipids are studied in a sub-group of diabetic patients. Liver biopsies from subjects with suspected non-alcoholic fatty liver disease are analyzed for sphingolipid synthesis enzyme expression. Dihydroceramides, contained in triglyceride-rich very-low-density lipoprotein (VLDL), are associated with steatosis and steatohepatitis. Expression of sphingolipid synthesis enzymes is correlated with histological steatosis and inflammation grades. In conclusion, association of plasma dihydroceramides with nonalcoholic fatty liver might explain their predictive character for type 2 diabetes. Our results suggest a relationship between hepatic sphingolipid metabolism and steatohepatitis and an involvement of dihydroceramides in the synthesis/secretion of triglyceride-rich VLDL, a hallmark of NAFLD and type 2 diabetes dyslipidemia.
血浆二氢神经酰胺是 2 型糖尿病的预测因子，与代谢功能障碍有关，但潜在机制尚不清楚。我们比较了两批糖尿病患者的血浆二氢神经酰胺与生化和肝脏参数之间的关系。通过其血浆生物标志物评估肝脂肪变性、脂肪性肝炎和纤维化。在一组糖尿病患者中研究了血浆脂蛋白神经酰胺。对疑似非酒精性脂肪性肝病患者的肝活检进行神经酰胺合成酶表达分析。富含甘油三酯的极低密度脂蛋白 (VLDL) 中的二氢神经酰胺与脂肪变性和脂肪性肝炎有关。神经酰胺合成酶的表达与组织学脂肪变性和炎症程度相关。总之，血浆二氢神经酰胺与非酒精性脂肪性肝病的关联可能解释了它们对 2 型糖尿病的预测特征。我们的结果表明，肝神经酰胺代谢与脂肪性肝炎之间存在关系，并且二氢神经酰胺参与富含甘油三酯的 VLDL 的合成/分泌，这是非酒精性脂肪性肝病和 2 型糖尿病血脂异常的特征。
