Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
C.N.R. Institute of Clinical Physiology, Pisa, Italy.
Front Endocrinol (Lausanne). 2020 Apr 17;11:216. doi: 10.3389/fendo.2020.00216. eCollection 2020.
N-acetylaspartate (NAA) is synthesized only by neurons and is involved in neuronal metabolism and axonal myelination. NAA is the strongest signal on brain magnetic resonance spectroscopy, and its concentration have been associated with cognitive dysfunction in neurodegenerative diseases, obesity, and type 2 diabetes (T2D). We explored the impact of obesity and T2D on circulating NAA as well as the impact of bariatric surgery and antidiabetic treatments. We developed an LC-MS method for the accurate measurements of fasting plasma NAA levels in 505 subjects (156 subjects with normal glucose tolerance, 24 subjects with impaired glucose tolerance, and 325 patients with T2D) to examine the associations of NAA with obesity and dysglycemia. To validate cross-sectional findings, plasma NAA was measured 6 months after Roux-en-Y Gastric Bypass (RYGB) in 55 morbidly obese subjects, and after 1 year of antidiabetic treatment (with dapagliflozin, exenatide, or dapagliflozin plus exenatide) in 192 T2D patients. In the whole population, NAA was associated with age ( = 0.31, <0.0001) and BMI ( = -0.20, <0.0001). Independently of age and BMI, NAA was reciprocally related to HbA1c and fasting plasma glucose (partial = -0.13, both = 0.01). Surgically-induced weight loss raised NAA (by 18 nmol/L on average, <0.02). Glucose lowering treatment increased NAA in proportion to the drop in HbA1c ( = 0.31, <0.0001) regardless of the agent used. Circulating NAA concentrations are modulated by age, obesity, and glycemic control. Whether they may mark for the corresponding metabolic effects on brain function remains to be established by joint measurements of spectroscopic signal and cognitive function.
N- 乙酰天冬氨酸（NAA）仅由神经元合成，参与神经元代谢和轴突髓鞘形成。NAA 是脑磁共振波谱中最强的信号，其浓度与神经退行性疾病、肥胖和 2 型糖尿病（T2D）中的认知功能障碍有关。我们探讨了肥胖和 T2D 对循环 NAA 的影响，以及减重手术和抗糖尿病治疗的影响。我们开发了一种 LC-MS 方法，用于准确测量 505 例受试者（156 例糖耐量正常、24 例糖耐量受损和 325 例 T2D 患者）的空腹血浆 NAA 水平，以研究 NAA 与肥胖和糖代谢异常的关系。为了验证横断面研究结果，在 55 例病态肥胖患者中测量了 Roux-en-Y 胃旁路（RYGB）术后 6 个月的血浆 NAA，并在 192 例 T2D 患者中测量了 1 年抗糖尿病治疗（使用达格列净、艾塞那肽或达格列净联合艾塞那肽）后的血浆 NAA。在全人群中，NAA 与年龄（ = 0.31， <0.0001）和 BMI（ = -0.20， <0.0001）相关。独立于年龄和 BMI，NAA 与 HbA1c 和空腹血糖呈反向相关（部分 = -0.13，均 = 0.01）。手术引起的体重减轻使 NAA 升高（平均升高 18 nmol/L， <0.02）。无论使用何种药物，降低 HbA1c 的幅度与 NAA 的增加成比例（ = 0.31， <0.0001）。循环 NAA 浓度受年龄、肥胖和血糖控制的调节。它们是否可以通过光谱信号和认知功能的联合测量来反映对大脑功能的相应代谢影响，还有待进一步确定。
