Lycopene Biodistribution Is Altered in 15,15´-Carotenoid Monooxygenase Knockout Mice3

Lindshield, Brian L.; King, Jennifer L.; Wyss, Adrian; Góralczyk, Regina; Lu, Chi‐Hua; Ford, Neil B.; Erdman, John W.

doi:10.3945/jn.108.099663

Cited by 39 publications

(35 citation statements)

References 31 publications

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“…Regardless, the b-cryptoxanthin gene score was significantly inversely associated with plasma retinol in the testing subset, and the b-carotene gene score, when weighted for retinol, was significantly associated with plasma retinol in all women with genotyped data for the relevant SNPs. Liver retinol stores may be more affected by BCMO1 variation, as suggested by the reduced liver vitamin A concentrations in b-carotene-fed BCMO1 knockout mice (31,32). Overall, our results support the hypothesis that BCMO1 variants affect provitamin A carotenoid conversion, presumably because of altered BCMO1 function (7,9).…”

Section: Discussionsupporting

confidence: 75%

β-Carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent

Hendrickson

Hazra²,

Chen³

et al. 2012

The American Journal of Clinical Nutrition

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Section: Discussionsupporting

confidence: 75%

β-Carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent

Hendrickson

Hazra²,

Chen³

et al. 2012

The American Journal of Clinical Nutrition

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“…This is consistent with the relevant findings from other groups (Amengual et al, 2013; dela Sena et al, 2013; Dela Sena et al, 2016; Lindqvist and Andersson, 2002; Lindshield et al, 2008; Mein et al, 2011; Wang, 2012). Our feeding data also revealed that in bco1 −/− /bco2 −/− mice, the retinal accumulation of xanthophylls lutein and zeaxanthin is around six times higher than retinal accumulation of β-carotene, while the hepatic β-carotene is around twenty times as much as the hepatic xanthophyll.…”

Section: Discussionsupporting

confidence: 93%

“…For the crystalline zeaxanthin bioavailability study, zeaxanthin was mixed with the vitamin-A-deficient AIN-93G diet (1 g/kg) prepared by Test Diet (St. Louis, MO, USA). Zeaxanthin encapsulated DSM ActiLease ® beadlets were mixed with a previously reported base diet (Lindshield et al, 2008) at a dosage of 1 g/kg of the base diet.…”

Section: Methodsmentioning

confidence: 99%

Retinal accumulation of zeaxanthin, lutein, and β-carotene in mice deficient in carotenoid cleavage enzymes

Vachali

Shen

et al. 2017

Experimental Eye Research

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Carotenoid supplementation can prevent and reduce the risk of age-related macular degeneration (AMD) and other ocular disease, but until now, there has been no validated and well-characterized mouse model which can be employed to investigate the protective mechanism and relevant metabolism of retinal carotenoids. β-Carotene oxygenases 1 and 2 (BCO1 and BCO2) are the only two carotenoid cleavage enzymes found in animals. Mutations of the bco2 gene may cause accumulation of xanthophyll carotenoids in animal tissues, and BCO1 is involved in regulation of the intestinal absorption of carotenoids. To determine whether or not mice deficient in BCO1 and/or BCO2 can serve as a macular pigment mouse model, we investigated the retinal accumulation of carotenoids in these mice when fed with zeaxanthin, lutein, or β-carotene using an optimized carotenoid feeding method. HPLC analysis revealed that all three carotenoids were detected in sera, livers, retinal pigment epithelium (RPE)/choroids, and retinas of all of the mice, except that no carotenoid was detectable in the retinas of wild type (WT) mice. Significantly higher amounts of zeaxanthin and lutein accumulated in the retinas of BCO2 knockout (bco2−/−) mice and BCO1/BCO2 double knockout (bco1−/−/bco2−/−) mice relative to BCO1 knockout (bco1−/−) mice, while bco1−/− mice preferred to take up β-carotene. The levels of zeaxanthin and lutein were higher than β-carotene levels in the bco1−/−/bco2−/− retina, consistent with preferential uptake of xanthophyll carotenoids by retina. Oxidative metabolites were detected in mice fed with lutein or zeaxanthin but not in mice fed with β-carotene. These results indicate that bco2−/− and bco1−/−/bco2−/− mice could serve as reasonable non-primate models for macular pigment function in the vertebrate eye, while bco1−/− mice may be more useful for studies related to β-carotene.

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“…Overall, we conclude that CMO-I and CMO-II appear to have pleiotropic roles in lipid metabolic homeostasis. We [24,29] and others [6–8,13] have established that tomato carotenoids are likely substrates of these enzymes. Additionally, the expression of CMO-I and CMO-II alter serum, adipose, and hepatic lipid products.…”

Section: Discussionmentioning

confidence: 99%

“…Total liver lipids were extracted using a modification of the Folch method [28,29]. Briefly, the liver sample (~0.3 g), n = 10 per group, was homogenized in chloroform: methanol (1:1) (Fisher Scientific, Pittsburg, PA.) and filtered by gravity.…”

Section: Methodsmentioning

confidence: 99%

Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulate carotenoid and lipid metabolism in mice

2013

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Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A while carotene-9’,10’-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that beta-carotene metabolites regulate dietary lipid uptake while lycopene regulates peroxisome-proliferated activator receptor (PPAR) expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations and lipid metabolism in female CMO-I−/− and CMO-II−/− mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I−/− mice had higher levels of leptin, insulin and hepatic lipidosis, but lower levels of serum cholesterol. CMO-II−/− mice had increased tissue lycopene and phytofluene accumulation, reduced IGF-1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with WT mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder did significantly decrease serum insulin-like growth factor-I. Tomato powder also reduced hepatic PPAR expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype, as well as tomato carotenoid-independent regulation of lipid metabolism.

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Lycopene Biodistribution Is Altered in 15,15´-Carotenoid Monooxygenase Knockout Mice3

Cited by 39 publications

References 31 publications

β-Carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent

β-Carotene 15,15′-monooxygenase 1 single nucleotide polymorphisms in relation to plasma carotenoid and retinol concentrations in women of European descent

Retinal accumulation of zeaxanthin, lutein, and β-carotene in mice deficient in carotenoid cleavage enzymes

Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulate carotenoid and lipid metabolism in mice

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