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 × 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).

中文翻译：

---

NAFLD 中氨基酸浓度的改变：肥胖和胰岛素抵抗的影响

非酒精性脂肪性肝病 (NAFLD) 中的血浆氨基酸 (AAs) 浓度，尤其是支链 AAs (BCAAs) 浓度通常会升高；然而，这是否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尚不清楚。因此，我们评估了 a) 与肥胖者 (NAFLD-Ob) 相比，无肥胖症 (NAFLD-NO) 的 NAFLD 受试者与对照组 (CT) 相比是否显示出改变的血浆 AA；b) 如果 AA 浓度与 IR 和肝脏组织学有关。已知 NAFLD 中的谷氨酸、丝氨酸和甘氨酸浓度会发生改变。因为这些 AA 参与谷胱甘肽合成，我们假设它们可能与 NAFLD 的严重程度有关。因此，我们通过气相色谱-质谱法、胰岛素抵抗的稳态模型评估，测量了 44 名无糖尿病且进行肝活检（29 名 NAFLD-NO 和 15 名 NAFLD-Ob）和 20 名无肥胖的 NAFLD 受试者的 AA 谱，肝脏 IR（Hep-IR；Hep-IR = 内源性葡萄糖生成 × 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]）并测试与肝脏组织学的关联。大多数 AA 仅在 NAFLD-Ob 受试者中增加。与 CT 相比，NAFLD-NO 受试者中仅丙氨酸、谷氨酸、异亮氨酸和缬氨酸增加，而亮氨酸不增加。谷氨酸、酪氨酸和 GSG 指数与 Hep-IR 相关。GSG 指数与肝酶相关，尤其是 γ-谷氨酰转移酶 (R = 0.70)，与体重指数无关。肝活检中的气球样变和/或炎症与血浆 BCAA 和芳香族 AA 的增加有关，并且与 GSG 指数轻度相关，而在该队列中，只有新的 GSG 指数能够区分纤维化 F3-4 和 F0-2。结论：主要在肥胖和 NAFLD 受试者中观察到血浆 AA 浓度增加，这可能是 IR 和蛋白质分解代谢增加的结果。GSG 指数是肝脏疾病严重程度的可能标志，与体重指数无关。（肝病学 2018 年；67：145-158）。主要在肥胖和 NAFLD 受试者中观察到血浆 AA 浓度增加，这可能是 IR 和蛋白质分解代谢增加的结果。GSG 指数是肝脏疾病严重程度的可能标志，与体重指数无关。（肝病学 2018 年；67：145-158）。主要在肥胖和 NAFLD 受试者中观察到血浆 AA 浓度增加，这可能是 IR 和蛋白质分解代谢增加的结果。GSG 指数是肝脏疾病严重程度的可能标志，与体重指数无关。（肝病学 2018 年；67：145-158）。