title: Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulate carotenoid and lipid metabolism in mice.
abstract: Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A, whereas carotene-9',10'-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that β-carotene metabolites regulate dietary lipid uptake, whereas lycopene regulates peroxisome proliferator-activated receptor 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 insulin-like growth factor 1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with wild-type mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder significantly decreased serum insulin-like growth factor 1. Tomato powder also increased hepatic peroxisome proliferator-activated receptor 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.
authors.affiliation: Department of Nutritional Sciences, University of Texas at Austin, Austin TX 78723, USA.
authors.forename: Nikki A
authors.initials: NA
authors.lastname: Ford
authors.forename: Amy C
authors.initials: AC
authors.lastname: Elsen
authors.forename: John W
authors.initials: JW
authors.lastname: Erdman
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage* / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004032:Diet; D044943:Fatty Acid Desaturases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006728:Hormones / Q000097:blood; D007249:Inflammation / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010641:Phenotype; D011208:Powders / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics* / Q000378:metabolism
chemical_list: D006728:Hormones; D011208:Powders; D012333:RNA, Messenger; C519530:insulin-like growth factor-1, mouse; D019207:beta Carotene; D002338:Carotenoids; D007334:Insulin-Like Growth Factor I; C003140:phytofluene; D002784:Cholesterol; C493359:Bco1 protein, mouse; D044943:Fatty Acid Desaturases; C554481:carotene-9',10'-monooxygenase, mouse; D050559:beta-Carotene 15,15'-Monooxygenase; D000077276:Lycopene
keywords: CMO-I; CMO-II; Cholesterol; IGF-1; Lipids; Lycopene; Mice; PPAR; Phytoene; RXR; SNP; Tomato; WT; carotene-15,15′-monooxygenase; carotene-9′,10′-monooxygenase; insulin-like growth factor 1; mRNA; messenger RNA; peroxisome proliferator-activated receptor; retinoid X receptor; single nucleotide polymorphism; wild-type
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