Background: This study profiles ceramides extracted from visceral and subcutaneous adipose tissue of human subjects by liquid chromatography-mass spectrometry to determine a correlation with status of diabetes and gender.
Methods: Samples of visceral and abdominal wall subcutaneous adipose tissue (n = 36 and n = 31, respectively) were taken during laparoscopic surgery from 36 patients (14 nondiabetic, 22 diabetic and prediabetic) undergoing bariatric surgery with a body mass index (BMI) >35 kg/m2 with ≥1 existing comorbidity or BMI ≥40 kg/m2 . Sphingolipids were extracted and analyzed using liquid chromatography-mass spectrometry.
Results: After logarithm 2 conversion, paired analysis of visceral to subcutaneous tissue showed differential accumulation of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in visceral tissue of prediabetic/diabetic female subjects, but not in males. Within-tissue analysis showed higher mean levels of ceramide species linked to insulin resistance, such as Cer(d18:1/18:0) and Cer(d18:1/16:0), in visceral tissue of prediabetic/diabetic patients compared with nondiabetic subjects and higher content of Cer(d18:1/14:0) in subcutaneous tissue of insulin-resistant female patients compared with prediabetic/diabetic males. Statistically significant differences in mean levels of ceramide species between insulin-resistant African American and insulin-resistant Caucasian patients were not evident in visceral or subcutaneous tissue.
Conclusions: Analysis of ceramides is important for developing a better understanding of biological processes underlying type 2 diabetes, metabolic syndrome, and obesity. Knowledge of the accumulated ceramides/dihydroceramides may reflect on the prelipolytic state that leads the lipotoxic phase of insulin resistance and may shed light on the predisposition to insulin resistance by gender.
目的: 采用液相色谱-质谱分析从受试者内脏和皮下脂肪组织中提取的神经酰胺, 以确定神经酰胺与糖尿病状态和性别的相关性。 方法: 在腹腔镜手术中采集36例内脏和31例腹壁皮下脂肪组织标本, 这些标本来自36位患者, 其中14位非糖尿病, 22例糖尿病及糖尿病前期患者, 体重指数>35 kg/m2 并有超过1种合并症, 或体重指数≥40 kg/m2 。采用液相色谱-质谱联用技术对鞘磷脂进行提取和分析。 结果: Log2转换后, 内脏和皮下组织的配对分析显示Cer(d18:1/16:0), Cer(d18:1/18:0)和Cer(d18:1/24:1)在糖尿病前期/糖尿病女性受试者的内脏组织中有不同程度的蓄积, 而男性则没有。组织内分析显示, 糖尿病前期/糖尿病患者内脏组织中与胰岛素抵抗相关的神经酰胺类物质如Cer(d18:1/18:0)和Cer(d18:1/16:0)的平均水平高于非糖尿病患者, 而胰岛素抵抗女性患者皮下组织中Cer (d18:1/14:0) 的含量高于糖尿病前期/糖尿病男性患者。在胰岛素抵抗的非裔美国人和胰岛素抵抗的高加索人之间, 神经酰胺的平均水平在内脏或皮下组织中没有明显的统计学差异。 结论: 神经酰胺的分析对于更好地了解2型糖尿病, 代谢综合征和肥胖的生物学过程很重要。对积累的神经酰胺/二氢神经酰胺的了解可以反映导致胰岛素抵抗的脂毒性阶段的脂解前状态, 并可能揭示性别对胰岛素抵抗的易感性。.
Keywords: adipose tissue; adiposity; ceramides; diabetes; gender; insulin resistance; 性别; 神经酰胺; 糖尿病; 肥胖; 胰岛素抵抗; 脂肪组织.
© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.