Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S]
Obesity-associated chronic inflammation contributes to metabolic dysfunction and propagates atherosclerosis. Recent evidence suggests that increased dietary cholesterol exacerbates inflammation in adipose tissue and liver, contributing to the proatherogenic milieu. The ability of the citrus flavonoi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-03-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520419352 |
| _version_ | 1818734972735848448 |
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| author | Julia M. Assini Erin E. Mulvihill Brian G. Sutherland Dawn E. Telford Cynthia G. Sawyez Sarah L. Felder Sanjiv Chhoker Jane Y. Edwards Robert Gros Murray W. Huff |
| author_facet | Julia M. Assini Erin E. Mulvihill Brian G. Sutherland Dawn E. Telford Cynthia G. Sawyez Sarah L. Felder Sanjiv Chhoker Jane Y. Edwards Robert Gros Murray W. Huff |
| author_sort | Julia M. Assini |
| collection | DOAJ |
| description | Obesity-associated chronic inflammation contributes to metabolic dysfunction and propagates atherosclerosis. Recent evidence suggests that increased dietary cholesterol exacerbates inflammation in adipose tissue and liver, contributing to the proatherogenic milieu. The ability of the citrus flavonoid naringenin to prevent these cholesterol-induced perturbations is unknown. To assess the ability of naringenin to prevent the amplified inflammatory response and atherosclerosis induced by dietary cholesterol, male Ldlr−/− mice were fed either a cholesterol-enriched high-fat or low-fat diet supplemented with 3% naringenin for 12 weeks. Naringenin, through induction of hepatic fatty acid (FA) oxidation and attenuation of FA synthesis, prevented hepatic steatosis, hepatic VLDL overproduction, and hyperlipidemia induced by both cholesterol-rich diets. Naringenin attenuated hepatic macrophage infiltration and inflammation stimulated by dietary cholesterol. Insulin resistance, adipose tissue expansion, and inflammation were alleviated by naringenin. Naringenin attenuated the cholesterol-induced formation of both foam cells and expression of inflammatory markers in peritoneal macrophages. Naringenin significantly decreased atherosclerosis and inhibited the formation of complex lesions, which was associated with normalized aortic lipids and a reversal of aortic inflammation. We demonstrate that in mice fed cholesterol-enriched diets, naringenin attenuates peripheral and systemic inflammation, leading to protection from atherosclerosis. These studies offer a therapeutically relevant alternative for the prevention of cholesterol-induced metabolic dysregulation. |
| first_indexed | 2024-12-18T00:13:51Z |
| format | Article |
| id | doaj.art-158247674e644e5aa756021704b6e7ce |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T00:13:51Z |
| publishDate | 2013-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-158247674e644e5aa756021704b6e7ce2022-12-21T21:27:34ZengElsevierJournal of Lipid Research0022-22752013-03-01543711724Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S]Julia M. Assini0Erin E. Mulvihill1Brian G. Sutherland2Dawn E. Telford3Cynthia G. Sawyez4Sarah L. Felder5Sanjiv Chhoker6Jane Y. Edwards7Robert Gros8Murray W. Huff9Vascular Biology, Robarts Research Institute; Department of BiochemistryVascular Biology, Robarts Research Institute; Department of BiochemistryVascular Biology, Robarts Research InstituteVascular Biology, Robarts Research Institute; Department of MedicineVascular Biology, Robarts Research Institute; Department of MedicineVascular Biology, Robarts Research Institute; Department of BiochemistryVascular Biology, Robarts Research Institute; Department of BiochemistryVascular Biology, Robarts Research Institute; Department of MedicineVascular Biology, Robarts Research Institute; Department of Medicine; Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, CanadaTo whom correspondence should be addressed. e-mail: mhuff@uwo.ca.; Vascular Biology, Robarts Research Institute; Department of Biochemistry; Department of MedicineObesity-associated chronic inflammation contributes to metabolic dysfunction and propagates atherosclerosis. Recent evidence suggests that increased dietary cholesterol exacerbates inflammation in adipose tissue and liver, contributing to the proatherogenic milieu. The ability of the citrus flavonoid naringenin to prevent these cholesterol-induced perturbations is unknown. To assess the ability of naringenin to prevent the amplified inflammatory response and atherosclerosis induced by dietary cholesterol, male Ldlr−/− mice were fed either a cholesterol-enriched high-fat or low-fat diet supplemented with 3% naringenin for 12 weeks. Naringenin, through induction of hepatic fatty acid (FA) oxidation and attenuation of FA synthesis, prevented hepatic steatosis, hepatic VLDL overproduction, and hyperlipidemia induced by both cholesterol-rich diets. Naringenin attenuated hepatic macrophage infiltration and inflammation stimulated by dietary cholesterol. Insulin resistance, adipose tissue expansion, and inflammation were alleviated by naringenin. Naringenin attenuated the cholesterol-induced formation of both foam cells and expression of inflammatory markers in peritoneal macrophages. Naringenin significantly decreased atherosclerosis and inhibited the formation of complex lesions, which was associated with normalized aortic lipids and a reversal of aortic inflammation. We demonstrate that in mice fed cholesterol-enriched diets, naringenin attenuates peripheral and systemic inflammation, leading to protection from atherosclerosis. These studies offer a therapeutically relevant alternative for the prevention of cholesterol-induced metabolic dysregulation.http://www.sciencedirect.com/science/article/pii/S0022227520419352cholesterolflavonoidlipidsobesityhepatic steatosisinsulin resistance |
| spellingShingle | Julia M. Assini Erin E. Mulvihill Brian G. Sutherland Dawn E. Telford Cynthia G. Sawyez Sarah L. Felder Sanjiv Chhoker Jane Y. Edwards Robert Gros Murray W. Huff Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] Journal of Lipid Research cholesterol flavonoid lipids obesity hepatic steatosis insulin resistance |
| title | Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] |
| title_full | Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] |
| title_fullStr | Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] |
| title_full_unstemmed | Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] |
| title_short | Naringenin prevents cholesterol-induced systemic inflammation, metabolic dysregulation, and atherosclerosis in Ldlr−/− mice[S] |
| title_sort | naringenin prevents cholesterol induced systemic inflammation metabolic dysregulation and atherosclerosis in ldlr mice s |
| topic | cholesterol flavonoid lipids obesity hepatic steatosis insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520419352 |
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