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Loss of carotene-9',10'-monooxygenase expression increases serum and tissue lycopene concentrations in lycopene-fed mice.

ABSTRACT: Two enzymes have been identified for the oxidative metabolism of carotenoids in mammals. Carotene-15,15'-monooxygenase (CMO-I) primarily centrally cleaves ?,?-carotene to form vitamin A. We hypothesize that carotene-9',10'-monooxygenase (CMO-II) plays a key role in metabolism of acyclic nonprovitamin A carotenoids such as lycopene. We investigated carotenoid bioaccumulation in young adult, male, wild-type (WT) mice or mice lacking CMO-II (CMO-II KO). Mice were fed an AIN-93G diet or identical diets supplemented with 10% tomato powder, 130 mg lycopene/kg diet (10% lycopene beadlets), or placebo beadlets for 4 or 30 d. Lycopene preferentially accumulated in CMO-II KO mouse tissues and serum compared with WT mouse tissues. ?-Carotene preferentially accumulated in some CMO-II KO mouse tissues compared with WT mouse tissues. Relative tissue mRNA expression of CMO-I and CMO-II was differentially expressed in mouse tissues, and CMO-II, but not CMO-I, was expressed in mouse prostate. In conclusion, the loss of CMO-II expression leads to increased serum and tissue concentrations of lycopene in tomato-fed mice.

SUBMITTER: Ford NA

PROVIDER: S-EPMC2981000 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Loss of carotene-9',10'-monooxygenase expression increases serum and tissue lycopene concentrations in lycopene-fed mice.

Ford Nikki A NA Clinton Steven K SK von Lintig Johannes J Wyss Adrian A Erdman John W JW

The Journal of nutrition 20101020 12

Two enzymes have been identified for the oxidative metabolism of carotenoids in mammals. Carotene-15,15'-monooxygenase (CMO-I) primarily centrally cleaves β,β-carotene to form vitamin A. We hypothesize that carotene-9',10'-monooxygenase (CMO-II) plays a key role in metabolism of acyclic nonprovitamin A carotenoids such as lycopene. We investigated carotenoid bioaccumulation in young adult, male, wild-type (WT) mice or mice lacking CMO-II (CMO-II KO). Mice were fed an AIN-93G diet or identical di ...[more]

PMID: 20962153

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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.

Project description:BackgroundThe consumption and blood concentrations of lycopene are both positively and inversely associated with the risk of several chronic diseases. The inconsistences in lycopene disease association studies may stem from a lack of knowledge about the genetic variation in the synthesis, metabolism, and deposition of transport and binding proteins, which potentially influence serum lycopene concentrations.ObjectiveWe examined the association between variation across the genome and serum concentrations of lycopene in a multiethnic population.MethodsParticipants included African (n = 914), Hispanic (n = 464), and European (n = 1203) American postmenopausal women from the Women's Health Initiative. We analyzed ∼7 million single nucleotide polymorphisms (SNPs). Linear regression models were used to assess associations between each SNP and serum concentrations (log transformed, continuous) of lycopene; we adjusted for age, body mass index, and population substructure. Models were run separately by ethnicity, and results were combined in a transethnic fixed-effects meta-analysis.ResultsIn the meta-analysis, the scavenger receptor class B, member 1 (SCARB1) gene, which encodes for a cholesterol membrane transporter, was significantly associated with lycopene concentrations (rs1672879; P < 2.68 × 10(-9)). Each additional G allele resulted in a 12% decrease in lycopene concentrations for African Americans, 20% decrease for Hispanic Americans, and 9% decrease for European Americans. In addition, 2 regions were significantly associated with serum lycopene concentrations in African Americans: the slit homolog 3 gene (SLIT3), which serves as a molecular guidance cue in cellular migration, and the dehydrogenase/reductase (SDR family) member 2 (DHRS2) gene, which codes for an oxidoreductase that mitigates the breakdown of steroids.ConclusionsWe found 3 novel loci associated with serum lycopene concentrations, 2 of which were specific to African Americans. Future functional studies looking at these specific genes may provide insight into the metabolism and underlying function of lycopene in humans, which may further elucidate lycopene's influence on disease risk and health. This trial was registered at clinicaltrials.gov as NCT00000611.

Dataset Information

Loss of carotene-9',10'-monooxygenase expression increases serum and tissue lycopene concentrations in lycopene-fed mice.

Publications

Loss of carotene-9',10'-monooxygenase expression increases serum and tissue lycopene concentrations in lycopene-fed mice.

Similar Datasets

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