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Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation

Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and sever...

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Autores principales: Sampey, Brante P., Freemerman, Alex J., Zhang, Jimmy, Kuan, Pei-Fen, Galanko, Joseph A., O'Connell, Thomas M., Ilkayeva, Olga R., Muehlbauer, Michael J., Stevens, Robert D., Newgard, Christopher B., Brauer, Heather A., Troester, Melissa A., Makowski, Liza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373493/
https://www.ncbi.nlm.nih.gov/pubmed/22701716
http://dx.doi.org/10.1371/journal.pone.0038812
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author Sampey, Brante P.
Freemerman, Alex J.
Zhang, Jimmy
Kuan, Pei-Fen
Galanko, Joseph A.
O'Connell, Thomas M.
Ilkayeva, Olga R.
Muehlbauer, Michael J.
Stevens, Robert D.
Newgard, Christopher B.
Brauer, Heather A.
Troester, Melissa A.
Makowski, Liza
author_facet Sampey, Brante P.
Freemerman, Alex J.
Zhang, Jimmy
Kuan, Pei-Fen
Galanko, Joseph A.
O'Connell, Thomas M.
Ilkayeva, Olga R.
Muehlbauer, Michael J.
Stevens, Robert D.
Newgard, Christopher B.
Brauer, Heather A.
Troester, Melissa A.
Makowski, Liza
author_sort Sampey, Brante P.
collection PubMed
description Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome.
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spelling pubmed-33734932012-06-14 Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation Sampey, Brante P. Freemerman, Alex J. Zhang, Jimmy Kuan, Pei-Fen Galanko, Joseph A. O'Connell, Thomas M. Ilkayeva, Olga R. Muehlbauer, Michael J. Stevens, Robert D. Newgard, Christopher B. Brauer, Heather A. Troester, Melissa A. Makowski, Liza PLoS One Research Article Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to “Cafeteria diets" (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome. Public Library of Science 2012-06-12 /pmc/articles/PMC3373493/ /pubmed/22701716 http://dx.doi.org/10.1371/journal.pone.0038812 Text en Sampey 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sampey, Brante P.
Freemerman, Alex J.
Zhang, Jimmy
Kuan, Pei-Fen
Galanko, Joseph A.
O'Connell, Thomas M.
Ilkayeva, Olga R.
Muehlbauer, Michael J.
Stevens, Robert D.
Newgard, Christopher B.
Brauer, Heather A.
Troester, Melissa A.
Makowski, Liza
Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title_full Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title_fullStr Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title_full_unstemmed Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title_short Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation
title_sort metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373493/
https://www.ncbi.nlm.nih.gov/pubmed/22701716
http://dx.doi.org/10.1371/journal.pone.0038812
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