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Title:Lutein and α-tocopherol biodistribution in animal models
Author(s):Jeon, Sookyoung
Director of Research:Erdman , John W
Doctoral Committee Chair(s):Jeffery, Elizabeth H
Doctoral Committee Member(s):Nakamura, Manabu T; Johnson, Elizabeth J
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):lutein
α-tocopherol
biodistribution
Abstract:Carotenoids and vitamin E (α-Tocopherol; αT), the two most plentiful groups of lipophilic antioxidants in plants, serve important functions in the human body. The carotenoid lutein is prevalent in green leafy vegetables and is one of the most abundant carotenoids in serum and tissues. Of particular interest for this thesis, lutein may have critical roles in visual and cognitive functions; αT may help maintain neurological health. Since neither component is endogenously synthesized by humans, their tissue deposition is solely determined by dietary sources. Accumulating evidence have shown that their selective accumulation can suggest their functional roles in tissues, especially in the eyes or brain. This dissertation sought to elucidate the bioavailability and tissue bioaccumulation of lutein and αT in appropriate animal models. In Chapter 2, we explored the bioaccumulation of lutein in infant rhesus macaques fed formulas with high or low levels of carotenoids (lutein, zeaxanthin, β-carotene and lycopene) for 4 months (n=2/group). All samples were analyzed by HPLC-PDA. This pilot study supports our hypothesis that the carotenoid-supplemented infant formula substantially enhanced lutein accumulation in various tissues. Since we used only a total of 4 animals and did not have a breastfed control group, we performed a larger study in Chapter 3. In Chapter 3, we investigated the bioaccumulation of lutein in infant rhesus macaques following breastfeeding or formula feeding. From birth to 6 months, male and female rhesus macaques (Macaca mulatta) were either breastfed (n=8), fed a formula supplemented with lutein, zeaxanthin, β-carotene and lycopene (n=8), or fed a formula with low levels of these carotenoids (n=7). The levels of carotenoids in serum and tissues were analyzed by HPLC-PDA. Breastfed infant rhesus macaques demonstrated higher lutein concentrations in serum and brain regions, retina, and other tissues than in formula-fed monkeys, despite similar lutein concentrations in the breast milk and carotenoid supplemented formula. Carotenoid supplementation in infant formula enhanced lutein deposition in serum and multiple tissues including all examined brain areas, but not in the macular retina. In Chapter 4, we asked if the enhanced lutein bioaccumulation in retina (macula and periphery) and brain (occipital cortex and cerebellum) of breastfed, compared to formula-fed, infant monkeys was associated with higher levels of serum total and HDL cholesterol, apolipoproteins, or mRNA/protein expression of carotenoid-related genes (CD36, SCARB1, SCARB2, LDLR, STARD3, GSTP1, BCO1, BCO2, or RPE65). Dietary regimen did not impact the expression of carotenoid-related genes except for SCARB2. However, carotenoid-related genes were differentially expressed across brain and retina regions. Breastfed infants had higher serum total and HDL cholesterol, and apolipoproteins than formula-fed infants, suggesting that lipoprotein levels might be important for delivering lutein to tissues, especially the macular retina, during infancy. In Chapter 5, we demonstrated the distribution of lutein into tissues of an adult rhesus macaque after a single oral dose of isotopically-labeled lutein. One 19-year-old female macaque was supplemented daily for a year with 1 μmol/kg/day of unlabeled lutein and subsequently provided a single oral dose of 1.92 mg of highly enriched 13C-lutein. Plasma, six brain regions, retina, and other tissues were collected on the third day post-dose. Lutein accumulation was quantified by HPLC-PDA and 13C enrichment was evaluated by LC-Q-TOF-MS. 13C-lutein was differentially distributed across various tissues, including multiple brain regions, but was undetectable in the retina. We demonstrated that distribution of lutein in the macaque is substantially dependent on tissue type. In Chapter 6, to prepare for a forthcoming pharmacokinetics study with 13C-αT, we evaluated the effects of a tocopherol-stripped diet on αT tissue accumulation using wild-type (C57BL/6J) mice. Three-week-old weanling mice were fed a tocopherol-stripped diet for either one, two, or three weeks during their rapid growth phase (beginning at weaning). At each time point, tissue αT concentrations were analyzed by HPLC-PDA. We found that three weeks of tocopherol-stripped diet decreased αT concentrations in most tissues, but not in the brain, of rapidly growing wild-type mice. In conclusion, we elucidated lutein biodistribution profiles in infant monkeys who were breastfed or formula-fed for six months, as well as one possible mechanism to explain the differential accumulation of lutein in primate retina and brain. In addition, we determined tissue bioaccumulation patterns of a single dose of 13C-lutein using an adult nonhuman primate model. Additionally, we verified that a tocopherol-stripped diet for 3 weeks decreases αT levels in tissues of growing wild-type mice. Using this model, we will perform an additional study to investigate the time-course accumulation of 13C-natural or synthetic αT in various tissues. Altogether, this dissertation has contributed novel findings to our understanding of the bioavailability and bioaccumulation of lutein and αT in appropriate animal models.
Issue Date:2018-08-29
Type:Text
URI:http://hdl.handle.net/2142/102886
Rights Information:Copyright 2018 Sookyoung Jeon
Date Available in IDEALS:2019-02-08
Date Deposited:2018-12


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