title: Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism.
abstract: Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals.
authors.affiliation: Departments of Biochemistry School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Palczewski
authors.affiliation: Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: M Airanthi K
authors.initials: MA
authors.lastname: Widjaja-Adhi
authors.affiliation: Department of Cell Biology, School of Medicine, New York University, New York, NY.
authors.forename: Jaume
authors.initials: J
authors.lastname: Amengual
authors.affiliation: Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Marcin
authors.initials: M
authors.lastname: Golczak
authors.affiliation: Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH jxv99@case.edu.
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood* / Q000235:genetics; D004032:Diet; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood* / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D014975:Lutein / Q000008:administration & dosage / Q000097:blood; D008660:Metabolism / Q000235:genetics; D051379:Mice; D059467:Transcriptome / Q000235:genetics*; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D065146:Zeaxanthins / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood
chemical_list: D008055:Lipids; D014280:Triglycerides; D065146:Zeaxanthins; D019207:beta Carotene; D002338:Carotenoids; D002784:Cholesterol; D014975:Lutein
keywords: cholesterol; lipoproteins; liver; microarray; triglyceride; zeaxanthin; β,β-carotene-15,15′-oxygenase; β,β-carotene-9′,10′-oxygenase; β-carotene