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

Nutr Res. 2013 Sep;33(9):733-42. doi: 10.1016/j.nutres.2013.07.007. Epub 2013 Aug 13.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Carotenoids / administration & dosage*
  • Carotenoids / blood
  • Cholesterol / blood
  • Diet*
  • Fatty Acid Desaturases / genetics*
  • Fatty Acid Desaturases / metabolism
  • Female
  • Genotype
  • Hormones / blood
  • Inflammation / pathology
  • Insulin-Like Growth Factor I / metabolism
  • Lipid Metabolism / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Lycopene
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size
  • Phenotype
  • Powders / chemistry
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Solanum lycopersicum / chemistry*
  • beta Carotene / administration & dosage
  • beta Carotene / blood
  • beta-Carotene 15,15'-Monooxygenase / genetics*
  • beta-Carotene 15,15'-Monooxygenase / metabolism

Substances

  • Hormones
  • Powders
  • RNA, Messenger
  • insulin-like growth factor-1, mouse
  • beta Carotene
  • Carotenoids
  • Insulin-Like Growth Factor I
  • phytofluene
  • Cholesterol
  • Bco1 protein, mouse
  • Fatty Acid Desaturases
  • carotene-9',10'-monooxygenase, mouse
  • beta-Carotene 15,15'-Monooxygenase
  • Lycopene