ABSTRACT
Objective To provide a basis for clinical diagnosis,a serum metabonomic dynamic study was carried out on the Tg2576 mouse model at different stages of Alzheimer's disease(AD) whose pathological progress is similar to that of human AD patients.Methods Serum samples of Tg2576 mice were collected at the early(6 months) and late(12 months) stages of Alzheimer's disease.The 1H NMR spectra of the serum samples were collected and the metabolic characteristics were analyzed by multivariate analysis.Results Significant differences in serum metabonomics were found in the transgenic Tg2576 mice and C57 mice at 6 and 12 months of age,and there were significant metabolic changes in Tg2576 mice at different stages of Alzheimer's disease.Compared with C57 mice,the Tg2576 mice at early stage of Alzheimer's disease showed higher levels of serum lactate,myo-inositol and amino acids(such as leucine,isoleucine,alanine),and lower levels of lipids,choline,phosphorylcholine,glycerol phosphorglcholine,betaine,glycine and glucose.At the late stage of Alzheimer's disease,the transgenic Tg2576 mice had higher levels of lactate,myo-inositol and alanine,while the serum levels of lipids,choline,phosphorylcholine,glycerophosphorylcholine,betaine,and glycine continued to drop.Meanwhile glutamine and creatine levels started to decline.By comparing the early and late serum metabolites of Alzheimer's disease,serum metabonomic profiles of the late stage of Alzheimer's disease indicated an up-regulation of lactate,myo-inositol and alanine,and a down-regulation of lipids,choline,phosphorylcholine and glycerophosphorylcholinelevels.Moreover,the levels of lactate,lipids,choline,phosphorylcholine and glycerophosphorylcholine showed statistical significance at the early stage of AD,and they were closely correlated with the severity of Alzheimer's disease.Conclusions The above results show that the changes of lactate,myo-inositol and alanine are positively-correlated with the development of AD,while the serum levels of lipids,choline,phosphorylcholine and glycerophosphorylcholine are inversely-proportional to the severity of AD.These metabolites are dynamically and progressively changed along with the disease progression,which hopefully may serve as early metabolic markers for the diagnosis of AD in clinical practice.
ABSTRACT
<p><b>OBJECTIVE</b>To study the metabolic changes of pancreatic extracts from insulin-resistant rats induced by fructose feeding using nuclear magnetic resonance ¹H spectroscopy (¹H NMR).</p><p><b>METHODS</b>Sixteen Wistar rats were divided equally into control group and model group and given water and 10% fructose water for 8 weeks, respectively. The pancreatic tissues were then obtained for H NMR spectra analysis and principal component analysis (PCA).</p><p><b>RESULTS</b>Compared with the control rats, the rats in the model group showed significantly increased creatine, betaine/TMAO, taurine, glycine and myo-inositol and decreased levels of lipids, lactate, glutamate, choline and GPC/PC.</p><p><b>CONCLUSION</b>¹H NMR and pattern recognition can define the metabolic characteristics of the pancreatic tissue extracts from insulin-resistant rats and provide reliable metabolic evidence for studying the mechanisms of insulin resistance at the molecular level.</p>
Subject(s)
Animals , Rats , Fructose , Insulin Resistance , Metabolomics , Pancreatic Extracts , Chemistry , Principal Component Analysis , Proton Magnetic Resonance Spectroscopy , Rats, WistarABSTRACT
Metabolic characteristics of 39 human brain tumor tissues, including 15 astrocytomas, 13 fibroblastic meningiomas and 11 transitional meningiomas from 39 individual patients, have been studied using high resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy in conjunction with principal component analysis (PCA). With rich metabolite information, 1H NMR spectra showed that the tumor-tissuc metabonome was dominated by lipids, lactate, myo-inositol, ereatine, choline metabolites such as choline, phosphocholine and glycerophosphocholine, amino acids such as alanine, glutamate, glutamine, taurine, N-acetyl-aspartate and glutathione. PCA of the tumor NMR spectra clearly showed metabonomic differences between low-grade astrocytomas and meningiomas whereas such differences were more moderate between fibroblastic and transitional meningiomas. Compared with meningiomas, the low-grade astrocytomas had higher levels of glycerophosphocholine, phosphocholine, myo-inositol and creatine but lower levels of alanine, glutamate, glutamine, glutathione and taurine. The N-acetyl-aspartate level was low but detectable in low-grade astrocytomas whereas it was not detectable in meningiomas. It is concluded that tissue metabonomics technology consisting of HRMAS 1H NMR spectroscopy and multivariate data analysis (MVDA) offers a useful tool (1) for distinguishing different types of brain tumors, (2) for providing the metabolic information for human brain tumors, which are potentially useful for understanding biochemistry of tumor progression.