Prashath Saranya
Centre for Genomic and Child Health, Queen Mary University of London, 4 Newark St, London, UK.
Amino Acids. 2025 Aug 5;57(1):39. doi: 10.1007/s00726-025-03467-0.
L-arginine (L-Arg) is metabolised in the cell to generate nitric oxide (NO) and citrulline via nitric oxide synthase (NOS). NO is an important cellular signalling molecule that regulates lipid and glucose metabolism. The biological availability of NO is affected by the NOS inhibitor; N-nitro-L-Arg methyl ester (L-NAME) and the external NO donor; S-nitroso-N-acetyl-D, L-penicillamine (SNAP). Mouse adipocyte 3T3 L1 cells were cultured with 0, 400 and 800 µM L-Arg or control complete DMEM media. The impact of L-NAME (4 mM), and SNAP (100 µM) was also analysed. The cell fitness was similar and the mRNA levels of AMPK was increased and ACC-1 was decreased, whilst the activation of AMPK and ACC-1 was decreased upon the addition of exogenous L-Arg. Transcript and protein levels of AMPK and ACC-1 were regulated by addition of L-NAME and SNAP, however the impact of these targets was related to the concentration of L-Arg added to the cells and the culture time point of analysis. NO in the form of NO in cell culture supernatant was elevated in 400 and 800 µM L-Arg cultures. L-NAME significantly inhibited NO production from adipose cells in a time-dependent manner and subsequently impacted AMPK and ACC expression. Associated with these changes were changed in the concentration of L-Arg, L-Cit and L-Orn in the culture media. Collectively, these results show that excess L-Arg is sensed by the cell which then regulates AMPK and ACC-1 expression in response. The findings could have implications in modulation of signalling pathways for treating obesity and obesity induced diabetic mellitus.
L-精氨酸（L-Arg）在细胞内通过一氧化氮合酶（NOS）代谢生成一氧化氮（NO）和瓜氨酸。NO是一种重要的细胞信号分子，可调节脂质和葡萄糖代谢。NO的生物利用度受NOS抑制剂N-硝基-L-精氨酸甲酯（L-NAME）和外源性NO供体S-亚硝基-N-乙酰-D，L-青霉胺（SNAP）的影响。将小鼠脂肪细胞3T3 L1细胞与0、400和800 μM的L-Arg或对照完全DMEM培养基一起培养。还分析了L-NAME（4 mM）和SNAP（100 μM）的影响。细胞适应性相似，AMPK的mRNA水平升高，ACC-1的mRNA水平降低，而添加外源性L-Arg后AMPK和ACC-1的激活降低。添加L-NAME和SNAP可调节AMPK和ACC-1的转录和蛋白质水平，然而这些靶点的影响与添加到细胞中的L-Arg浓度以及分析的培养时间点有关。在400和800 μM L-Arg培养物中，细胞培养上清液中NO形式的NO升高。L-NAME以时间依赖性方式显著抑制脂肪细胞中NO的产生，随后影响AMPK和ACC的表达。与这些变化相关的是培养基中L-Arg、L-瓜氨酸和L-鸟氨酸浓度的变化。总体而言，这些结果表明细胞能够感知过量的L-Arg，然后相应地调节AMPK和ACC-1的表达。这些发现可能对治疗肥胖症和肥胖症诱发的糖尿病的信号通路调节具有重要意义。
