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Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma
Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a stud...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358346/ https://www.ncbi.nlm.nih.gov/pubmed/35959507 http://dx.doi.org/10.1177/11786388221111126 |
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author | Yan, Lin Rust, Bret M Sundaram, Sneha Picklo, Matthew J Bukowski, Michael R |
author_facet | Yan, Lin Rust, Bret M Sundaram, Sneha Picklo, Matthew J Bukowski, Michael R |
author_sort | Yan, Lin |
collection | PubMed |
description | Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a study showing that MCP-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma (LLC) to the lungs in mice fed a high-fat diet (HFD). In a 2 × 2 design, wild-type (WT) or Mcp-1 knockout (Mcp-1(-/-)) mice maintained on the AIN93G standard diet or HFD were subcutaneously injected with LLC cells to induce lung metastasis. We identified 87 metabolites for metabolomic analysis from this study. Amino acid metabolism was altered considerably in the presence of LLC metastases with the aminoacyl-tRNA biosynthesis pathways as the leading pathway altered. The HFD modified lipid and energy metabolism, evidenced by lower contents of arachidonic acid, cholesterol, and long-chain saturated fatty acids and higher contents of glucose and pyruvic acid in mice fed the HFD. These findings were supported by network analysis showing alterations in fatty acid synthesis and glycolysis/gluconeogenesis pathways between the 2 diets. Furthermore, elevations of the citrate cycle intermediates (citric acid, fumaric acid, isocitric acid, and succinic acid) and glyceric acid in Mcp-1(-/-) mice, regardless of diet, suggest the involvement of MCP-1 in mitochondrial energy metabolism during LLC metastasis. The present study demonstrates that MCP-1 deficiency and the HFD altered plasma metabolome in mice bearing LLC metastases. These findings can be useful in understanding the impact of obesity on prevention and treatment of cancer metastasis. |
format | Online Article Text |
id | pubmed-9358346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-93583462022-08-10 Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma Yan, Lin Rust, Bret M Sundaram, Sneha Picklo, Matthew J Bukowski, Michael R Nutr Metab Insights Original Research Article Both clinical and laboratory studies have shown that monocyte chemotactic protein-1 (MCP-1) is involved in cancer spread. To understand the role of MCP-1 in metabolism in the presence of metastasis, we conducted an untargeted metabolomic analysis of primary metabolism on plasma collected from a study showing that MCP-1 deficiency reduces spontaneous metastasis of Lewis lung carcinoma (LLC) to the lungs in mice fed a high-fat diet (HFD). In a 2 × 2 design, wild-type (WT) or Mcp-1 knockout (Mcp-1(-/-)) mice maintained on the AIN93G standard diet or HFD were subcutaneously injected with LLC cells to induce lung metastasis. We identified 87 metabolites for metabolomic analysis from this study. Amino acid metabolism was altered considerably in the presence of LLC metastases with the aminoacyl-tRNA biosynthesis pathways as the leading pathway altered. The HFD modified lipid and energy metabolism, evidenced by lower contents of arachidonic acid, cholesterol, and long-chain saturated fatty acids and higher contents of glucose and pyruvic acid in mice fed the HFD. These findings were supported by network analysis showing alterations in fatty acid synthesis and glycolysis/gluconeogenesis pathways between the 2 diets. Furthermore, elevations of the citrate cycle intermediates (citric acid, fumaric acid, isocitric acid, and succinic acid) and glyceric acid in Mcp-1(-/-) mice, regardless of diet, suggest the involvement of MCP-1 in mitochondrial energy metabolism during LLC metastasis. The present study demonstrates that MCP-1 deficiency and the HFD altered plasma metabolome in mice bearing LLC metastases. These findings can be useful in understanding the impact of obesity on prevention and treatment of cancer metastasis. SAGE Publications 2022-08-04 /pmc/articles/PMC9358346/ /pubmed/35959507 http://dx.doi.org/10.1177/11786388221111126 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Article Yan, Lin Rust, Bret M Sundaram, Sneha Picklo, Matthew J Bukowski, Michael R Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung Carcinoma |
title | Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte
Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung
Carcinoma |
title_full | Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte
Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung
Carcinoma |
title_fullStr | Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte
Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung
Carcinoma |
title_full_unstemmed | Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte
Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung
Carcinoma |
title_short | Alteration in Plasma Metabolome in High-Fat Diet-Fed Monocyte
Chemotactic Protein-1 Knockout Mice Bearing Pulmonary Metastases of Lewis Lung
Carcinoma |
title_sort | alteration in plasma metabolome in high-fat diet-fed monocyte
chemotactic protein-1 knockout mice bearing pulmonary metastases of lewis lung
carcinoma |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358346/ https://www.ncbi.nlm.nih.gov/pubmed/35959507 http://dx.doi.org/10.1177/11786388221111126 |
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