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Naringenin enhances the regression of atherosclerosis induced by a chow diet in Ldlr-/- mice.

Authors
  • Burke, Amy C1
  • Sutherland, Brian G2
  • Telford, Dawn E3
  • Morrow, Marisa R2
  • Sawyez, Cynthia G3
  • Edwards, Jane Y3
  • Huff, Murray W4
  • 1 Molecular Medicine, Robarts Research Institute, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada; Department of Biochemistry, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada. , (Canada)
  • 2 Molecular Medicine, Robarts Research Institute, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada. , (Canada)
  • 3 Molecular Medicine, Robarts Research Institute, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada; Department of Medicine, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada. , (Canada)
  • 4 Molecular Medicine, Robarts Research Institute, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada; Department of Biochemistry, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada; Department of Medicine, The University of Western Ontario, 1151 Richmond St N., London, Ontario, N6A 5B7, Canada. Electronic address: [email protected] , (Canada)
Type
Published Article
Journal
Atherosclerosis
Publication Date
May 09, 2019
Volume
286
Pages
60–70
Identifiers
DOI: 10.1016/j.atherosclerosis.2019.05.009
PMID: 31102954
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Naringenin is a citrus-derived flavonoid with lipid-lowering and insulin-sensitizing effects leading to athero-protection in Ldlr-/- mice fed a high-fat diet. However, the ability of naringenin to promote atherosclerosis regression is unknown. In the present study, we assessed the capacity of naringenin to enhance regression in Ldlr-/- mice with diet-induced intermediate atherosclerosis intervened with a chow diet. Male Ldlr-/- mice were fed a high-fat, cholesterol-containing (HFHC) diet for 12 weeks to induce intermediate atherosclerosis and metabolic dysfunction. Subsequently, a group of these mice were sacrificed for baseline analyses and the remainder either 1) continued on the HFHC diet, 2) switched to a chow diet or 3) switched to chow diet supplemented with naringenin. After 12 weeks induction, intermediate lesions developed in the aortic sinus. Intervention with chow alone slowed lesion growth, while intervention with naringenin-supplemented chow completely halted lesion growth. Lesions were characterized by features of improved morphology. Compared to chow alone, naringenin reduced plaque macrophages and modestly increased smooth muscle cells. Investigating processes that contributed to improved plaque morphology, we showed naringenin further reduced plasma triglycerides and cholesterol compared to chow alone. Furthermore, elevated monocytosis and myelopoiesis were further corrected by intervention with naringenin compared to chow alone. Metabolically, naringenin enhanced the correction of insulin resistance, hepatic steatosis and obesity compared to chow alone, potentially contributing to enhanced regression. Naringenin supplementation to chow enhances atherosclerosis regression in male Ldlr-/- mice. These studies further underscore the potential therapeutic utility of naringenin. Copyright © 2019 Elsevier B.V. All rights reserved.

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