title: Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis.
abstract: Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5B7; email: aburke42@uwo.ca ; mhuff@uwo.ca.|Current address: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5T 3L9; email: erin.mulvihill@utoronto.ca.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Mulvihill
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5B7; email: aburke42@uwo.ca ; mhuff@uwo.ca.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Burke
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, ON, Canada N6A 5B7; email: aburke42@uwo.ca ; mhuff@uwo.ca.|Department of Medicine, Robarts Research Institute, University of Western Ontario, London, ON, Canada N6A 5B7.
authors.forename: Murray W
authors.initials: MW
authors.lastname: Huff
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019440:Anti-Obesity Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002957:Citrus / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D019587:Dietary Supplements; D005419:Flavonoids / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000178:diet therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D050177:Overweight / Q000178:diet therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D000975:Antioxidants; D005419:Flavonoids; D000960:Hypolipidemic Agents; D008074:Lipoproteins
keywords: adipose tissue; atherosclerosis; citrus flavonoids; glucose metabolism; inflammation; lipid metabolism