Department of Gastroenterology, Cleveland Clinic, Cleveland, OH 44195, USA.
Metabolism. 2011 Jun;60(6):776-81. doi: 10.1016/j.metabol.2010.07.027. Epub 2010 Sep 23.
Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are produced by breakdown of proteins that have been methylated posttranslationally at an arginine residue. Plasma levels of ADMA are elevated in insulin resistance states. Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and varying degrees of hepatic dysfunction. Because ADMA is metabolized in the liver, we hypothesized that ADMA levels will be high in patients with NAFLD as a consequence of hepatic dysfunction and insulin resistance. Plasma levels of ADMA, SDMA, total homocysteine, glucose, and insulin were measured in nondiabetic patients with biopsy-proven NAFLD (11 steatosis and 24 nonalcoholic steatohepatitis) and 25 healthy subjects. Plasma ADMA levels were significantly higher (P = .029) in patients with biopsy-proven NAFLD (0.43 ± 0.21 μmol/L) compared with controls (0.34 ± 0.10 μmol/L). However, when adjusted for insulin resistance (homeostasis model assessment), the difference between 2 groups was not evident. Plasma SDMA levels were similar in all 3 groups. Plasma levels of ADMA were positively correlated with plasma total homocysteine levels (P = .003). Plasma levels of SDMA were negatively correlated with estimated glomerular filtration rate (P = .016) and positively correlated with plasma total homocysteine levels (P = .003). The ratio of ADMA/SDMA was positively correlated with body mass index (P = .027). Elevated plasma concentrations of ADMA in biopsy-proven NAFLD were primarily related to insulin resistance. Hepatic dysfunction in NAFLD does not appear to make significant contribution to changes in plasma methylarginine levels.
不对称二甲基精氨酸 (ADMA) 和对称二甲基精氨酸 (SDMA) 是由精氨酸残基翻译后甲基化的蛋白质分解产生的。ADMA 的血浆水平在胰岛素抵抗状态下升高。非酒精性脂肪性肝病 (NAFLD) 与胰岛素抵抗和不同程度的肝功能障碍有关。由于 ADMA 在肝脏中代谢，我们假设由于肝功能障碍和胰岛素抵抗，NAFLD 患者的 ADMA 水平会升高。在经活检证实的非酒精性脂肪性肝病 (11 例单纯性脂肪变性和 24 例非酒精性脂肪性肝炎) 和 25 例健康对照者中测量了非糖尿病患者的血浆 ADMA、SDMA、总同型半胱氨酸、葡萄糖和胰岛素水平。与对照组 (0.34 ± 0.10 μmol/L) 相比，经活检证实的非酒精性脂肪性肝病患者的血浆 ADMA 水平明显升高 (P =.029；0.43 ± 0.21 μmol/L)。然而，当调整胰岛素抵抗 (稳态模型评估) 后，两组之间的差异并不明显。三组的血浆 SDMA 水平相似。血浆 ADMA 水平与血浆总同型半胱氨酸水平呈正相关 (P =.003)。血浆 SDMA 水平与估计肾小球滤过率呈负相关 (P =.016)，与血浆总同型半胱氨酸水平呈正相关 (P =.003)。ADMA/SDMA 比值与体重指数呈正相关 (P =.027)。经活检证实的非酒精性脂肪性肝病患者血浆 ADMA 浓度升高主要与胰岛素抵抗有关。NAFLD 中的肝功能障碍似乎不会对血浆甲基精氨酸水平的变化产生显著影响。
