Seoul, Republic of Korea.
Richmond, VA, USA.
Aliment Pharmacol Ther. 2020 Nov;52(10):1603-1614. doi: 10.1111/apt.16066. Epub 2020 Sep 6.
Non-alcoholic fatty liver disease (NAFLD) affects obese and non-obese individuals. However, mechanisms underlying non-obese non-alcoholic steatohepatitis (NASH) remain unclear.
To attempt to identify metabolic perturbations associated with non-obese and obese NAFLD using a lipidomics approach.
A cross-sectional analysis of 361 subjects with biopsy-proven NAFLD (157 NAFL and 138 NASH) and healthy controls (n = 66) was performed. Individuals were categorised as obese or non-obese based on the Asian cut-off for body mass index. Circulating lipidomic profiling of sera was performed based on the histological severity of NAFLD. Circulating lipidomic alterations were validated with an independent validation set (154 NAFLD subjects [93 NAFL and 61 NASH] and 21 healthy controls).
Saturated sphingomyelin (SM) species were significantly associated with visceral adiposity in non-obese NAFLD (SM d38:0; P < 0.001) but not in obese NAFLD. Additionally, SM levels were significantly associated with systemic and adipose tissue insulin resistance (SM d38:0; P = 0.002 and <0.001, respectively). Five potential lipid metabolites for non-obese subjects and seven potential lipids for obese subjects were selected to predict NAFLD and NASH. These lipid combinations showed good diagnostic performance for non-obese (area under the curve [AUC] for NAFLD/NASH = 0.916/0.813) and obese (AUC for NAFLD/NASH = 0.967/0.812) subjects. Moreover, distinctly altered patterns of diacylglycerol (DAG), triacylglycerol (TAG) and SM levels were confirmed in the validation set depending on the histological severity of NAFLD.
Non-obese and obese NAFLD subjects exhibit unique circulating lipidomic signatures, including DAGs, TAGs and SMs. These lipid combinations may be useful biomarkers for non-obese and obese NAFLD patients.
非酒精性脂肪性肝病（NAFLD）影响肥胖和非肥胖个体。然而，非肥胖性非酒精性脂肪性肝炎（NASH）的发病机制仍不清楚。
尝试使用脂质组学方法来鉴定与非肥胖性和肥胖性 NAFLD 相关的代谢改变。
对 361 例经肝活检证实的 NAFLD（157 例 NAFL 和 138 例 NASH）患者和 66 例健康对照者进行了横断面分析。根据亚洲人 BMI 切点将个体分为肥胖或非肥胖。根据 NAFLD 的组织学严重程度对血清进行循环脂质组学分析。采用独立验证集（154 例 NAFLD 患者[93 例 NAFL 和 61 例 NASH]和 21 例健康对照）对循环脂质组学改变进行验证。
饱和鞘氨醇（SM）种类与非肥胖性 NAFLD 的内脏肥胖显著相关（SM d38：0；P<0.001），但与肥胖性 NAFLD 无关。此外，SM 水平与全身和脂肪组织胰岛素抵抗显著相关（SM d38：0；P=0.002 和<0.001）。选择了 5 种非肥胖者的潜在脂质代谢物和 7 种肥胖者的潜在脂质来预测 NAFLD 和 NASH。这些脂质组合对非肥胖者（NAFLD/NASH 的 AUC 为 0.916/0.813）和肥胖者（NAFLD/NASH 的 AUC 为 0.967/0.812）具有良好的诊断性能。此外，在验证集中根据 NAFLD 的组织学严重程度，确认了二酰基甘油（DAG）、三酰基甘油（TAG）和 SM 水平的明显改变模式。
非肥胖性和肥胖性 NAFLD 患者表现出独特的循环脂质组学特征，包括 DAG、TAG 和 SM。这些脂质组合可能是用于非肥胖性和肥胖性 NAFLD 患者的有用生物标志物。
