| Backgrounds: Type2diabetes mellitus (T2DM) has been a serious healthproblem to the public over the world, and its incidence increased fleetly year afteryear in recent years. The overall incidence in the adults has reached9.7%in China.The complications caused by T2DM could lead to death or disability. It’s a great harmto people’s health. The pathogenic mechanism of T2DM has not been completelyexplained. Currently it has been accepted what T2DM isn’t a single disease, but akind of syndrome caused by composite factors. Dietary factors play a very importantrole in the reasons. The obesity rodent models fed with high fat fodder were oftenused to study the pathogenesis of diabetes. But the previous studies have shown thatthe Wistar rats in the same homologous genetic background, fed with high fat dietare,performing a different phenotype—obesity and besity-resistance. Metabonomictechnology could analyse metabilites and metabolic intermediates in the biofluidqualitativly and quantitatively to discover dysbolism in the disease process, which notonly help us understand the metabolic pathways of the disease process and substanceof the body better, but also contribute to the discovery of disease biomarkers andsupporting clinical diagnostic purposes. The literature about high-fat diet leading toobesity and type2diabetes has been reported, but the non-obese type2diabetes isstill very limited. In this study, in order to studying high-fat diet causedobesity-resistant material and energy metabolism of Wistar rats obesity-resistant ratsby analyzing serum and urine metabolic fingerprint,screening biological markers, we interfere the s high-fat diet of Wistar rat intervention in16weeks and constructed ananalysis by GC-MS-based metabolomics. After the serum sample of urine bypre-treatment, in order to looking for differences in metabolites, a betterunderstanding of the pathogenesis of obese-resistance type2diabetes and othermetabolic diseases, The data collected after the peak matching, normalized correction,orthogonal signal correction (OSC) was used to multivariate analysis.Objective: In order to understand the pathogenesis of type2diabetes and othermetabolic diseases better in non-obese more, the method of analysis by GC-MS-basedmetabolomics was established, the high fat diet intervention in obesity-resistantmaterial and energy metabolism of Wistar rats were studied and serum, urinedifferences in metabolite were searched.Methods: A obesity resistant rat model was constructed and the biochemicalcriteria (the level of fasting plasma glucose, triglyceride，total cholesterol，highdensity lipoprotein and lower density lipoprotein) were analyzed.Results: The metabolites in the urine were exhaustively separated and detectedby GC-MS. Multivariate metabonomics analysis was performed after peak alignment.Collected data were transformed, the peak alignment between differentchromatograms was performed to generate the peak table, then orthogonal signalcorrection filtered partial least-squares discriminate analysis (OSC-PLS-DA) wascarried out to model the data(R2=0.929, Q2=0.905) and discover metabolites with asignificant concentration change in the obesity resistant rats. Compared with thecontrols, the obesity resistant rats showed lower levels of glycolic acid, serine,threonine, butane diacid, fumaric acid,2,3-dihydroxy-butyric acid, malic acid,carbonyl glutaric acid, p-hydroxybenzoic acid, p-hydroxyphenyl acetic acid, glucitol,trans-aconitic acid, fructose, glucose, inositol, meantime the serumsugar(4.19±0.47vs6.48±1.16) and insuline(4.29±0.58vs6.20±1.35) incressed.Compared with control rats, the obesity resistant rats showed clear metabolismdysfunctions of glucose, lipid and amino acid, pyruvate, succinate, fumarat, citric acid,myristic acid, uric acid were decreased. And serum sugar, insuline，low-densitylipoprotein and total cholesterol was significantly increased (4.19±0.47vs6.48±1.16, 4.29±0.58vs6.20±1.35,0.33±0.06vs1.34±1.01,1.55±0.18vs3.60±2.21), highdensity lipoprotein, triglyceride decreased significantly (0.77±0.11vs0.47±0.25,0.68±0.15vs0.42±0.17).Conclusions: After16weeks, the obesity resistant rats showed clear metabolicdysfunctions of glucose, lipid and amino acid. The results showed that GC-MS basedmetabonomics analysis could be helpful for understanding the mechanism of thenon-obese metabolic disease. High-density lipoprotein, LDL, total cholesterol, uricacid, arachidonic acid and were abnormal which were important to understand thepathogenesis of type2diabetes and other metabolic diseases better in non-obesemore. |
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