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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3373493?pdf=render |
| _version_ | 1828530199942135808 |
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| author | Brante P Sampey Alex J Freemerman Jimmy Zhang Pei-Fen Kuan Joseph A Galanko Thomas M O'Connell Olga R Ilkayeva Michael J Muehlbauer Robert D Stevens Christopher B Newgard Heather A Brauer Melissa A Troester Liza Makowski |
| author_facet | Brante P Sampey Alex J Freemerman Jimmy Zhang Pei-Fen Kuan Joseph A Galanko Thomas M O'Connell Olga R Ilkayeva Michael J Muehlbauer Robert D Stevens Christopher B Newgard Heather A Brauer Melissa A Troester Liza Makowski |
| author_sort | Brante P Sampey |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T22:19:46Z |
| format | Article |
| id | doaj.art-8123c07fdc0d45b6ac1702b037a95c4d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:19:46Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8123c07fdc0d45b6ac1702b037a95c4d2022-12-22T00:48:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3881210.1371/journal.pone.0038812Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation.Brante P SampeyAlex J FreemermanJimmy ZhangPei-Fen KuanJoseph A GalankoThomas M O'ConnellOlga R IlkayevaMichael J MuehlbauerRobert D StevensChristopher B NewgardHeather A BrauerMelissa A TroesterLiza MakowskiObesity 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.http://europepmc.org/articles/PMC3373493?pdf=render |
| spellingShingle | Brante P Sampey Alex J Freemerman Jimmy Zhang Pei-Fen Kuan Joseph A Galanko Thomas M O'Connell Olga R Ilkayeva Michael J Muehlbauer Robert D Stevens Christopher B Newgard Heather A Brauer Melissa A Troester Liza Makowski Metabolomic profiling reveals mitochondrial-derived lipid biomarkers that drive obesity-associated inflammation. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3373493?pdf=render |
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