Dataset Information

Molecular aspects of ?, ?-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases.

ABSTRACT: Carotenoids, the carotenes and xanthophylls, are essential components in human nutrition. ?, ?-carotene-9', 10'-oxygenase 2 (BCO2), also named as ?, ?-carotene-9', 10'-dioxygenase 2 (BCDO2) catalyzes the asymmetrical cleavage of carotenoids, whereas ?, ?-carotene-15, 15'-monooxygenase (BCMO1) conducts the symmetrical cleavage of pro-vitamin A carotenoids into retinoid. Unlike BCMO1, BCO2 has a broader substrate specificity and has been considered an alternative way to produce vitamin A. In contrast to BCMO1, a cytoplasmic protein, BCO2 is located in the inner mitochondrial membrane. The difference in cellular compartmentalization may reflect the different substrate specificity and physiological functions with respect to BCMO1 and BCO2. The BCO2 gene mutations are proven to be associated with yellow color of skin and fat tissue and milk in livestock. Mutation in intron 2 of BCO2 gene is also supposed to be related to the expression of IL-18, a pro-inflammatory cytokine associated with obesity, cardiovascular diseases, and type 2 diabetes. Further, BCO2 is associated with the development of mitochondrial oxidative stress, macular degeneration, anemia, and hepatic steatosis. This review of the literature will mostly address recent updates regarding the role of BCO2 in carotenoid metabolism, and discuss the potential impacts of BCO2 protein and the mutations in mammalian diseases.

SUBMITTER: Wu L

PROVIDER: S-EPMC5068469 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Molecular aspects of β, β-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases.

Wu Lei L Guo Xin X Wang Weiqun W Medeiros Denis M DM Clarke Stephen L SL Lucas Edralin A EA Smith Brenda J BJ Lin Dingbo D

Experimental biology and medicine (Maywood, N.J.) 20160707 17

Carotenoids, the carotenes and xanthophylls, are essential components in human nutrition. β, β-carotene-9', 10'-oxygenase 2 (BCO2), also named as β, β-carotene-9', 10'-dioxygenase 2 (BCDO2) catalyzes the asymmetrical cleavage of carotenoids, whereas β, β-carotene-15, 15'-monooxygenase (BCMO1) conducts the symmetrical cleavage of pro-vitamin A carotenoids into retinoid. Unlike BCMO1, BCO2 has a broader substrate specificity and has been considered an alternative way to produce vitamin A. In contr ...[more]

PMID: 27390265

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Project description:BackgroundNonalcoholic fatty liver disease is positively associated with obesity and cardiovascular disease risk. Apo-10'-lycopenoic acid (APO10LA), a potential oxidation product of apo-10'-lycopenal that is generated endogenously by β-carotene-9',10'-oxygenase (BCO2) cleavage of lycopene, inhibited hepatic steatosis in BCO2-expressing mice.ObjectiveThe present study evaluated lycopene and APO10LA effects on hepatic steatosis in mice without BCO2 expression.MethodsMale and female BCO2-knockout (BCO2-KO) mice were fed a high saturated fat diet (HSFD) with or without APO10LA (10 mg/kg diet) or lycopene (100 mg/kg diet) for 12 wk.ResultsLycopene or APO10LA supplementation reduced hepatic steatosis incidence (78% and 72%, respectively) and severity in BCO2-KO male mice. Female mice did not develop steatosis, had greater hepatic total cholesterol (3.06 vs. 2.31 mg/g tissue) and cholesteryl ester (1.58 vs. 0.86 mg/g tissue), but had lower plasma triglyceride (TG) (229 vs. 282 mg/dL) and cholesterol (97.1 vs. 119 mg/dL) than male mice. APO10LA-mitigated steatosis in males was associated with reduced hepatic total cholesterol (18%) and activated sirtuin 1 signaling, which resulted in reduced fatty acids (FAs) and TG synthesis markers [stearoyl-coenzyme A (CoA) desaturase protein, 71%; acetyl-CoA carboxylase phosphorylation, 79%; AMP-activated protein kinase phosphorylation, 67%], and elevated cholesterol efflux genes (cytochrome P450 family 7A1, 65%; ATP-binding cassette transporter G5/8, 11%). These APO10LA-mediated effects were not mimicked by lycopene supplementation. Intriguingly, steatosis inhibition by lycopene induced peroxisome proliferator-activated receptor (PPAR)α- and PPARγ-related genes in mesenteric adipose tissue (MAT) that increases mitochondrial uncoupling [cell death-inducing DNA fragmentation factor, α subunit-like effector a, 55%; PR domain-containing 16, 47%; uncoupling protein 3 (Ucp3), 55%], FA β-oxidation (PPARα, 53%; very long chain acyl-CoA dehydrogenase, 38%), and uptake (FA transport protein 4, 29%; lipoprotein lipase 43%). Expressions of 10 MAT PPAR-related genes were inversely correlated with steatosis score, suggesting that lycopene reduced steatosis by increasing MAT FA utilization.ConclusionsOur data suggest that lycopene and APO10LA inhibit HSFD-induced steatosis in BCO2-KO male mice through differential mechanisms. Sex disparity of BCO2-KO mice was observed in the outcomes of HSFD-induced liver steatosis and plasma lipids.

Dataset Information

Molecular aspects of ?, ?-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases.

Publications

Molecular aspects of β, β-carotene-9', 10'-oxygenase 2 in carotenoid metabolism and diseases.

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