Nutrition Physiology, Technische Universität München, Gregor-Mendel-Str. 2, 85350 Freising, Germany.
J Diabetes Res. 2018 Apr 26;2018:1864865. doi: 10.1155/2018/1864865. eCollection 2018.
The New Zealand obese (NZO) mouse is a polygenic model for obesity and diabetes with obese females and obese, diabetes-prone males, used to study traits of the metabolic syndrome like type 2 diabetes mellitus (T2DM), obesity, and dyslipidaemia. By using LC-MS/MS, we here examine the suitability of this model to mirror tissue-specific changes in acylcarnitine (AC) and amino acid (AA) species preceding T2DM which may reflect patterns investigated in human metabolism. We observed high concentrations of fatty acid-derived ACs in 11 female mice, high abundance of branched-chain amino acid- (BCAA-) derived ACs in 6 male mice, and slight increases in BCAA-derived ACs in the remaining 6 males. Principal component analysis (PCA) including all ACs and AAs confirmed our hypothesis especially in plasma samples by clustering females, males with high BCAA-derived ACs, and males with slight increases in BCAA-derived ACs. Concentrations of insulin, blood glucose, NEFAs, and triacylglycerols (TAGs) further supported the hypothesis of high BCAA-derived ACs being able to mirror the onset of diabetic traits in male individuals. In conclusion, alterations in AC and AA profiles overlap with observations from human studies indicating the suitability of NZO mice to study metabolic changes preceding human T2DM.
新西兰肥胖（NZO）鼠是一种肥胖和糖尿病的多基因模型，具有肥胖雌性和肥胖、易患糖尿病的雄性，用于研究代谢综合征的特征，如 2 型糖尿病（T2DM）、肥胖和血脂异常。我们使用 LC-MS/MS 在此检查了该模型是否适合反映 T2DM 之前组织特异性酰基肉碱（AC）和氨基酸（AA）变化的情况，这可能反映了人类代谢研究中的模式。我们观察到 11 只雌性小鼠中存在高浓度的脂肪酸衍生 AC，6 只雄性小鼠中存在高丰度的支链氨基酸（BCAA）衍生 AC，其余 6 只雄性小鼠中 BCAA 衍生 AC 略有增加。包括所有 AC 和 AA 的主成分分析（PCA）特别在血浆样本中证实了我们的假设，即通过聚类雌性、高 BCAA 衍生 AC 的雄性和 BCAA 衍生 AC 略有增加的雄性来聚类。胰岛素、血糖、NEFAs 和三酰甘油（TAGs）的浓度进一步支持了高 BCAA 衍生 AC 能够反映男性个体糖尿病特征发生的假设。总之，AC 和 AA 谱的改变与人类研究的观察结果重叠，表明 NZO 小鼠适合研究人类 T2DM 之前的代谢变化。
