Browsing by Subject "Carotenoids"

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    Aster proteins mediate carotenoid transport in mammalian cells
    (National Academy of Science, 2022) Bandara, Sepalika; Ramkumar, Srinivasagan; Imanishi, Sanae; Thomas, Linda D.; Sawant, Onkar B.; Imanishi, Yoshikazu; von Lintig, Johannes; Ophthalmology, School of Medicine
    Some mammalian tissues uniquely concentrate carotenoids, but the underlying biochemical mechanism for this accumulation has not been fully elucidated. For instance, the central retina of the primate eyes displays high levels of the carotenoids, lutein, and zeaxanthin, whereas the pigments are largely absent in rodent retinas. We previously identified the scavenger receptor class B type 1 and the enzyme β-carotene-oxygenase-2 (BCO2) as key components that determine carotenoid concentration in tissues. We now provide evidence that Aster (GRAM-domain-containing) proteins, recently recognized for their role in nonvesicular cholesterol transport, engage in carotenoid metabolism. Our analyses revealed that the StART-like lipid binding domain of Aster proteins can accommodate the bulky pigments and bind them with high affinity. We further showed that carotenoids and cholesterol compete for the same binding site. We established a bacterial test system to demonstrate that the StART-like domains of mouse and human Aster proteins can extract carotenoids from biological membranes. Mice deficient for the carotenoid catabolizing enzyme BCO2 concentrated carotenoids in Aster-B protein-expressing tissues such as the adrenal glands. Remarkably, Aster-B was expressed in the human but not in the mouse retina. Within the retina, Aster-B and BCO2 showed opposite expression patterns in central versus peripheral parts. Together, our study unravels the biochemical basis for intracellular carotenoid transport and implicates Aster-B in the pathway for macula pigment concentration in the human retina.
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    Zeaxanthin Drives Dynamic Changes in the Mouse Metabolome Through Gut Microbiome Shift
    (Elsevier, 2021) Lu, Peiran; Wong, Siau Yen; Chai, Jianmin; Jasbi, Paniz; Wu, Lei; Lyu, Yi; Tang, Minghua; Smith, Brenda; Lucas, Edralin; Clarke, Stephen L.; Chowanadisai, Winyoo; Shen, Xinchun; He, Hui; Zhao, Jiangchao; Gu, Haiwei; Conway, Tyrrell; Wyss, Adrian; Lin, Dingbo; Obstetrics and Gynecology, School of Medicine
    Objectives: Zeaxanthin, an oxygenized carotenoid, exerts antioxidant properties in human nutrition and metabolism. Like other carotenoids, zeaxanthin is poorly absorbed in the small intestine. The large portion of zeaxanthin reaches the colon and is not fully recovered in the colon. In this study, we aimed to investigate the association of zeaxanthin intake with the gut microbiome homeostasis and metabolomic responses in mice. Methods: Six-week-old male and female C57BL/6J wild type (WT), beta-carotene oxygenase 2 (BCO2) knockout mice were fed with AIN93M chow diets supplemented with or without zeaxanthin (0.02% w/w) for 10 weeks. At the termination of the study, mice were fasted for 3 hrs prior to euthanization. Cecal contents, colon, serum, feces, and other tissues were collected for laboratory assessments.16S rRNA sequencing and LC-MS/MS were performed for gut microbiota profiling and serum and fecal metabolomics analysis, respectively. Results: Significant zeaxanthin accumulation occurred in BCO2 KO, but not WT mice. Zeaxanthin accumulation was associated with the alteration of colonic gut microbiota composition, for example, zeaxanthin-increased abundance in Lachnospiraceae, Proteobacteria, and Parabacteroides, indicating enhanced short-chain production, improved intestinal integrity, and anaerobic bacterial colonization. The results of fecal and serum metabolomics revealed that zeaxanthin significantly altered tyrosine metabolism, branched-chain fatty acid oxidation, fatty acid biosynthesis, and phospholipid biosynthesis, and suppressed levels of kynurenine and trimethylamine N-oxide (TMAO). Conclusions: The results suggested that zeaxanthin accumulation promotes gut microbiome homeostasis and alters the gut microbial metabolites as signals in stimulating the host-gut microbe interplay.