학술논문

Combining metabolomic non-targeted GC×GC-ToF-MS analysis and chemometric ASCA-based study of variances to assess dietary influence on type 2 diabetes development in a mouse model.
Document Type
Article
Source
Analytical & Bioanalytical Chemistry. Jan2015, Vol. 407 Issue 1, p343-354. 12p.
Subject
*TIME-of-flight mass spectrometry
*CHEMOMETRICS
*TYPE 2 diabetes
*ANIMAL models of diabetes
*LABORATORY mice
*HYPERGLYCEMIA
*ANALYSIS of variance
Language
ISSN
1618-2642
Abstract
Insulin resistance (IR) lies at the origin of type 2 diabetes. It induces initial compensatory insulin secretion until insulin exhaustion and subsequent excessive levels of glucose (hyperglycemia). A high-calorie diet is a major risk factor contributing to the development of this metabolic disease. For this study, a time-course experiment was designed that consisted of two groups of mice. The aim of this design was to reproduce the dietary conditions that parallel the progress of IR over time. The first group was fed with a high-fatty-acid diet for several weeks and followed by 1 week of a low-fatty-acid intake, while the second group was fed with a low-fatty-acid diet during the entire experiment. The metabolomic fingerprint of C3HeB/FeJ mice liver tissue extracts was determined by means of two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-ToF-MS). This article addresses the application of ANOVA-simultaneous component analysis (ASCA) to the found metabolomic profile. By performing hyphenated high-throughput analytical techniques together with multivariate chemometric methodology on metabolomic analysis, it enables us to investigate the sources of variability in the data related to each experimental factor of the study design (defined as time, diet and individual). The contribution of the diet factor in the dissimilarities between the samples appeared to be predominant over the time factor contribution. Nevertheless, there is a significant contribution of the time-diet interaction factor. Thus, evaluating the influences of the factors separately, as it is done in classical statistical methods, may lead to inaccurate interpretation of the data, preventing achievement of consistent biological conclusions. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]