OBJECTIVE: The aim of this study was to assess biologic pathways behind MASLD progression from steatosis to metabolic dysfunction-associated steatohepatitis (MASH) using non-targeted liquid chromatography-mass spectrometry analysis in 106 severely obese individuals (78 women, mean age 47.7 7 ± 9.2 years, body mass index 41.8 ± 4.3 kg/m²) undergoing laparoscopic Roux-en-Y gastric bypass.
RESULTS: We identified several metabolites that are associated with MASLD progression. Most importantly, we observed a decrease of lysophosphatidylcholines LPC(18:2), LPC(18:3), and LPC(20:3) and increase of xanthine when comparing those with steatosis to those with MASH. We found that indole propionic acid and threonine were negatively correlated to fibrosis, but not with the metabolic disturbances associated with cardiovascular risk. Xanthine, ketoleucine, and tryptophan were positively correlated to lobular inflammation and ballooning but also with insulin resistance, and dyslipidemia, respectively. The results did not change when taking into account the most important genetic risk factors of MASLD.
CONCLUSIONS: Our findings suggest that there are several separate biological pathways, some of them independent of insulin resistance and dyslipidemia, associating with MASLD.
目的:本研究的目的是使用非靶向液相色谱-质谱分析评估106例严重肥胖患者(78名女性,平均年龄47.77±9.2岁,体重指数41.8±4.3kg/m²)进行腹腔镜Roux-en-Y胃旁路术。
结果:我们确定了几种与MASLD进展相关的代谢物。最重要的是,我们观察到溶血磷脂酰胆碱LPC(18:2),LPC(18:3),和LPC(20:3)以及黄嘌呤的增加,将脂肪变性的人与MASH的人进行比较。我们发现吲哚丙酸和苏氨酸与纤维化呈负相关,但与心血管风险相关的代谢紊乱无关。黄嘌呤,酮亮氨酸,和色氨酸与小叶炎症和球囊扩张呈正相关,但也与胰岛素抵抗,和血脂异常,分别。考虑到MASLD最重要的遗传风险因素,结果没有变化。
结论:我们的研究结果表明,有几个独立的生物学途径,其中一些独立于胰岛素抵抗和血脂异常,与MASLD联系。