Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance
Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance
复制标题
DOI：
10.1002/hep.29465
复制
发表时间：
2018-01-01
期刊：
影响因子：
13.5
通讯作者：
Gastaldelli, Amalia
中科院分区：
文献类型：
--
作者：
Gaggini, Melania;Carli, Fabrizia;Gastaldelli, Amalia
非酒精性脂肪性肝病(NAFLD)患者血浆氨基酸(AAs)浓度升高，尤其是支链氨基酸(BCAA)浓度升高；然而，如果这是由于肌肉蛋白质分解代谢增加、肥胖和/或胰岛素抵抗(IR)增加或组织代谢受损所致，则尚不清楚。因此，我们评估了a)非肥胖组(NAFLD-NO)与肥胖组(NAFLD-Ob)相比，血浆AAs是否与对照组(CT)相比发生了变化；以及b)AA浓度是否与IR和肝脏组织学有关。已知在NAFLD中谷氨酸、丝氨酸和甘氨酸的浓度会发生变化。因为这些氨基酸参与谷胱甘肽的合成，我们推测它们可能与NAFLD的严重程度有关。因此，我们通过气相色谱-质谱仪、稳态胰岛素抵抗模型评估、肝脏IR(Hep-IR；Hep-IR=内源性葡萄糖生成x胰岛素)和新的谷氨酸-丝氨酸-甘氨酸(GSG)指数(谷氨酸/[丝氨酸+甘氨酸])，测量了44例无糖尿病的NAFLD患者和20例非肥胖者的AA谱，并测试了其与肝脏组织学的相关性。大多数AAs仅在NAFLD-Ob患者中升高。与非酒精性脂肪肝患者相比，非酒精性脂肪肝患者只有丙氨酸、谷氨酸、异亮氨酸和缬氨酸增加，而亮氨酸没有增加。谷氨酸、酪氨酸和GSG指数与Hep-IR相关。GSG指数与肝酶相关，特别是γ-谷氨酰转移酶(R=0.70)，与体重指数无关。肝活检时的气球和/或炎症与血浆支链氨基酸和芳香族氨基酸的增加有关，与GSG指数有轻微的相关性，而在该队列中，只有新的GSG指数能够区分F3-4和F0-2。结论：血浆AA浓度升高主要见于肥胖和NAFLD患者，可能是胰岛素抵抗和蛋白质分解代谢增加的结果。GSG指数可能是一个独立于体重指数的肝病严重程度的标志物。(《肝病》2018；67：145-158)。
Plasma concentrations of amino acids (AAs), in particular, branched chain AAs (BCAAs), are often found increased in nonalcoholic fatty liver disease (NAFLD); however, if this is due to increased muscular protein catabolism, obesity, and/or increased insulin resistance (IR) or impaired tissue metabolism is unknown. Thus, we evaluated a) if subjects with NAFLD without obesity (NAFLD-NO) compared to those with obesity (NAFLD-Ob) display altered plasma AAs compared to controls (CTs); and b) if AA concentrations are associated with IR and liver histology. Glutamic acid, serine, and glycine concentrations are known to be altered in NAFLD. Because these AAs are involved in glutathione synthesis, we hypothesized they might be related to the severity of NAFLD. We therefore measured the AA profile of 44 subjects with NAFLD without diabetes and who had a liver biopsy (29 NAFLD-NO and 15 NAFLD-Ob) and 20 CTs without obesity, by gas chromatography-mass spectrometry, homeostasis model assessment of insulin resistance, hepatic IR (Hep-IR; Hep-IR = endogenous glucose production x insulin), and the new glutamate-serine-glycine (GSG) index (glutamate/[serine + glycine]) and tested for an association with liver histology. Most AAs were increased only in NAFLD-Ob subjects. Only alanine, glutamate, isoleucine, and valine, but not leucine, were increased in NAFLD-NO subjects compared to CTs. Glutamate, tyrosine, and the GSG-index were correlated with Hep-IR. The GSG-index correlated with liver enzymes, in particular, gamma-glutamyltransferase (R = 0.70), independent of body mass index. Ballooning and/or inflammation at liver biopsy were associated with increased plasma BCAAs and aromatic AAs and were mildly associated with the GSG-index, while only the new GSG-index was able to discriminate fibrosis F3-4 from F0-2 in this cohort. Conclusion: Increased plasma AA concentrations were observed mainly in subjects with obesity and NAFLD, likely as a consequence of increased IR and protein catabolism. The GSG-index is a possible marker of severity of liver disease independent of body mass index. (Hepatology 2018;67:145-158).