Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.
Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome o...
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ftdoajarticles:oai:doaj.org/article:3d874961c8f44735b52076ce80aae544 2023-05-15T15:09:03+02:00 Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. Julio J Amaral Luis Caetano M Antunes Cristiana S de Macedo Katherine A Mattos Jun Han Jingxi Pan André L P Candéa Maria das Graças M O Henriques Marcelo Ribeiro-Alves Christoph H Borchers Euzenir N Sarno Patrícia T Bozza B Brett Finlay Maria Cristina V Pessolani 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002381 https://doaj.org/article/3d874961c8f44735b52076ce80aae544 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3744420?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002381 https://doaj.org/article/3d874961c8f44735b52076ce80aae544 PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2381 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002381 2022-12-31T16:23:10Z Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 8 e2381 |
institution |
Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Julio J Amaral Luis Caetano M Antunes Cristiana S de Macedo Katherine A Mattos Jun Han Jingxi Pan André L P Candéa Maria das Graças M O Henriques Marcelo Ribeiro-Alves Christoph H Borchers Euzenir N Sarno Patrícia T Bozza B Brett Finlay Maria Cristina V Pessolani Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases. |
format |
Article in Journal/Newspaper |
author |
Julio J Amaral Luis Caetano M Antunes Cristiana S de Macedo Katherine A Mattos Jun Han Jingxi Pan André L P Candéa Maria das Graças M O Henriques Marcelo Ribeiro-Alves Christoph H Borchers Euzenir N Sarno Patrícia T Bozza B Brett Finlay Maria Cristina V Pessolani |
author_facet |
Julio J Amaral Luis Caetano M Antunes Cristiana S de Macedo Katherine A Mattos Jun Han Jingxi Pan André L P Candéa Maria das Graças M O Henriques Marcelo Ribeiro-Alves Christoph H Borchers Euzenir N Sarno Patrícia T Bozza B Brett Finlay Maria Cristina V Pessolani |
author_sort |
Julio J Amaral |
title |
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
title_short |
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
title_full |
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
title_fullStr |
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
title_full_unstemmed |
Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
title_sort |
metabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002381 https://doaj.org/article/3d874961c8f44735b52076ce80aae544 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2381 (2013) |
op_relation |
http://europepmc.org/articles/PMC3744420?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002381 https://doaj.org/article/3d874961c8f44735b52076ce80aae544 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002381 |
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PLoS Neglected Tropical Diseases |
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7 |
container_issue |
8 |
container_start_page |
e2381 |
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1766340290109505536 |