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Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice
Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868278/ https://www.ncbi.nlm.nih.gov/pubmed/27183228 http://dx.doi.org/10.1371/journal.pone.0155776 |
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author | Horakova, Olga Hansikova, Jana Bardova, Kristina Gardlo, Alzbeta Rombaldova, Martina Kuda, Ondrej Rossmeisl, Martin Kopecky, Jan |
author_facet | Horakova, Olga Hansikova, Jana Bardova, Kristina Gardlo, Alzbeta Rombaldova, Martina Kuda, Ondrej Rossmeisl, Martin Kopecky, Jan |
author_sort | Horakova, Olga |
collection | PubMed |
description | Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. |
format | Online Article Text |
id | pubmed-4868278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48682782016-05-26 Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice Horakova, Olga Hansikova, Jana Bardova, Kristina Gardlo, Alzbeta Rombaldova, Martina Kuda, Ondrej Rossmeisl, Martin Kopecky, Jan PLoS One Research Article Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. Public Library of Science 2016-05-16 /pmc/articles/PMC4868278/ /pubmed/27183228 http://dx.doi.org/10.1371/journal.pone.0155776 Text en © 2016 Horakova et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Horakova, Olga Hansikova, Jana Bardova, Kristina Gardlo, Alzbeta Rombaldova, Martina Kuda, Ondrej Rossmeisl, Martin Kopecky, Jan Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title | Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title_full | Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title_fullStr | Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title_full_unstemmed | Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title_short | Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice |
title_sort | plasma acylcarnitines and amino acid levels as an early complex biomarker of propensity to high-fat diet-induced obesity in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868278/ https://www.ncbi.nlm.nih.gov/pubmed/27183228 http://dx.doi.org/10.1371/journal.pone.0155776 |
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