Tissue lycopene absorption and accumulation in transgenic mice lacking one or both carotenoid cleaving enzymes

-carotene oxygenase 1 (BCO1) and -carotene oxygenase 2 (BCO2) are responsible for the cleavage of carotenoids in mammals. The goals of this study were to establish the relative contribution of each enzyme on lycopene accumulation in mice. We utilized male and female wild-type (WT), Bco1-/-, Bco2-/-, and Bco1-/- Bco2-/- double knockout (DKO) mice. We gavaged the mice with either 1 mg of lycopene resuspended in cottonseed oil or vehicle as a control group daily for a period of two weeks. In a second study, we evaluated the effect of dietary vitamin A on lycopene absorption and intestinal gene expression. We evaluated lycopene concentration isomer distribution by HPLC and evaluated gene expression by RT-PCR analyses. Hepatic mitochondria were isolated to determine lycopene content and isomer characterization. Of the 11 tissues measured, the liver accounted for 94-98% of the lycopene content across genotypes. We did not observe sex differences between genotypes, although Bco1-/- hepatic lycopene levels were approximately half in comparison to the other genotypes; Bco1-/- verses Bco2-/- (p< 0.0001), DKO mice (p< 0.001), WT (ns). Analyses of mitochondrial lycopene content revealed a 3-5 fold enrichment in comparison to total hepatic content (p<0.05) in all genotypes and sexes. In our second study, WT mice fed a vitamin A-deficient diet (VAD) accumulated greater amounts of lycopene in the liver than those fed a vitamin A sufficient diet (VAS) (p<0.01). These changes were accompanied by an upregulation of the vitamin A-responsive transcription factor intestine-specific homeobox (ISX) in mice fed VAD + lycopene and VAS + lycopene diets in comparison to VAD control-fed mice (P<0.05). Our data suggests that BCO2 is the primary lycopene cleavage enzyme in mice. Lycopene concentration was enriched in the mitochondria of hepatocytes independently of genotype, and lycopene stimulates vitamin A signaling in WT mice.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Bradley, Madelyn

Contributors dc:contributor

• Erdman, John
• Amengual, Jaume
• Chen, Hong

• Lycopene
• Absorption
• Scavenger Receptor Class B Type 1
• Retinoic Acid
• Biodistribution.

Statement dc:rights

• Copyright 2023 Madelyn Bradley

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/120540

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F120540