Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production
Background: The mechanisms connecting dietary intake of processed foods with systemic inflammatory markers and cardiovascular risk remain poorly defined. We sought to compare the abundance of pro-inflammatory stimulants of innate immune receptors in processed foods with those produced by the murine...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01404/full |
| _version_ | 1818476632898273280 |
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| author | Tola A. Faraj Tola A. Faraj Cordula Stover Clett Erridge Clett Erridge |
| author_facet | Tola A. Faraj Tola A. Faraj Cordula Stover Clett Erridge Clett Erridge |
| author_sort | Tola A. Faraj |
| collection | DOAJ |
| description | Background: The mechanisms connecting dietary intake of processed foods with systemic inflammatory markers and cardiovascular risk remain poorly defined. We sought to compare the abundance of pro-inflammatory stimulants of innate immune receptors in processed foods with those produced by the murine ileal and caecal microbiota, and to explore the impact of their ingestion on systemic inflammation and lipid metabolism in vivo.Methods and results: Calibrated receptor-dependent reporter assays revealed that many processed foods, particularly those based on minced meats, contain pro-inflammatory stimulants of Toll-like receptor (TLR)-2 and TLR4 at concentrations which greatly exceed those produced by the endogenous murine ileal microbiota. Chronic dietary supplementation with these stimulants, at concentrations relevant to those measured in the Western diet, promoted hepatic inflammation and reduced several markers of reverse cholesterol transport (RCT) in mice. Hepatocytes were found to be insensitive to TLR2- and TLR4-stimulants directly, but their secretion of functional cholesterol acceptors was impaired by interleukin (IL)-1β released by TLR-responsive hepatic macrophages. Hepatic macrophage priming by high-fat diet enhanced the impairment of RCT by ingested endotoxin, and this was reversed by macrophage depletion via clodronate liposome treatment, or genetic deficiency in the IL-1 receptor.Conclusion: These findings reveal an unexpected mechanism connecting processed food consumption with cardiovascular risk factors, and introduce the food microbiota as a potential target for therapeutic regulation of lipid metabolism. |
| first_indexed | 2024-12-10T09:28:21Z |
| format | Article |
| id | doaj.art-a3adb113b5ae423f835d584a75645e01 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T09:28:21Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a3adb113b5ae423f835d584a75645e012022-12-22T01:54:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01404460249Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 ProductionTola A. Faraj0Tola A. Faraj1Cordula Stover2Clett Erridge3Clett Erridge4Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United KingdomDepartment of Pharmacognosy, Hawler Medical University, Erbil, IraqDepartment of Infection, Immunity and Inflammation, University of Leicester, Leicester, United KingdomDepartment of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, United KingdomSchool of Life Sciences, Anglia Ruskin University, Cambridge, United KingdomBackground: The mechanisms connecting dietary intake of processed foods with systemic inflammatory markers and cardiovascular risk remain poorly defined. We sought to compare the abundance of pro-inflammatory stimulants of innate immune receptors in processed foods with those produced by the murine ileal and caecal microbiota, and to explore the impact of their ingestion on systemic inflammation and lipid metabolism in vivo.Methods and results: Calibrated receptor-dependent reporter assays revealed that many processed foods, particularly those based on minced meats, contain pro-inflammatory stimulants of Toll-like receptor (TLR)-2 and TLR4 at concentrations which greatly exceed those produced by the endogenous murine ileal microbiota. Chronic dietary supplementation with these stimulants, at concentrations relevant to those measured in the Western diet, promoted hepatic inflammation and reduced several markers of reverse cholesterol transport (RCT) in mice. Hepatocytes were found to be insensitive to TLR2- and TLR4-stimulants directly, but their secretion of functional cholesterol acceptors was impaired by interleukin (IL)-1β released by TLR-responsive hepatic macrophages. Hepatic macrophage priming by high-fat diet enhanced the impairment of RCT by ingested endotoxin, and this was reversed by macrophage depletion via clodronate liposome treatment, or genetic deficiency in the IL-1 receptor.Conclusion: These findings reveal an unexpected mechanism connecting processed food consumption with cardiovascular risk factors, and introduce the food microbiota as a potential target for therapeutic regulation of lipid metabolism.https://www.frontiersin.org/article/10.3389/fimmu.2019.01404/fullmicrobiotainflammationinnate immunitycholesterol metabolismcardiovascular diseasediet |
| spellingShingle | Tola A. Faraj Tola A. Faraj Cordula Stover Clett Erridge Clett Erridge Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production Frontiers in Immunology microbiota inflammation innate immunity cholesterol metabolism cardiovascular disease diet |
| title | Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production |
| title_full | Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production |
| title_fullStr | Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production |
| title_full_unstemmed | Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production |
| title_short | Dietary Toll-Like Receptor Stimulants Promote Hepatic Inflammation and Impair Reverse Cholesterol Transport in Mice via Macrophage-Dependent Interleukin-1 Production |
| title_sort | dietary toll like receptor stimulants promote hepatic inflammation and impair reverse cholesterol transport in mice via macrophage dependent interleukin 1 production |
| topic | microbiota inflammation innate immunity cholesterol metabolism cardiovascular disease diet |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01404/full |
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