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Updated: Jul 11, 2026
Quantitative Analysis of Dietary Vitamin A Metabolites in Murine Ocular and Non-Ocular Tissues Using High-Performance Liquid Chromatography
Published on: December 27, 2024
CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice
Susanne Hessel1, Anne Eichinger2, Andrea Isken1
1Institute of Biology I, Animal Physiology and Neurobiology, Hauptstrasse 1, D-79104 Freiburg, Germany.
Abstract:
Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant-derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15'-oxygenase (CMO1) and a putative carotenoid-9',10'-oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing beta-carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in beta-carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1(-/-) mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor gamma-regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism.
Insights
Carotenoid-15,15'-oxygenase (CMO1) is crucial for converting beta-carotene into vitamin A. CMO1 deficiency in mice impairs vitamin A production and disrupts lipid metabolism, leading to fatty liver and altered serum lipids.
Area of Science:
- Biochemistry
- Human Physiology
- Nutritional Science
Background:
- Carotenoids are vital plant compounds investigated for chronic disease prevention and combating vitamin A deficiency.
- Mammals possess two carotenoid-cleaving enzymes: carotenoid-15,15'-oxygenase (CMO1) and carotenoid-9',10'-oxygenase (CMO2).
- CMO1 is the primary enzyme responsible for converting provitamin A carotenoids into retinol (vitamin A).
Purpose of the Study:
- To elucidate the physiological role of CMO1 in mammals.
- To investigate the impact of CMO1 deficiency on vitamin A metabolism and overall homeostasis.
- To explore potential broader roles of carotenoids beyond vitamin A production.
Main Methods:
- Targeted homologous recombination was used to generate a CMO1-deficient mouse model (CMO1-/-).
- Mice were fed diets with beta-carotene as the primary vitamin A source.
- Vitamin A levels, carotenoid accumulation, lipid profiles, and gene expression (PPAR-gamma) were analyzed in various tissues.
Main Results:
- CMO1(-/-) mice exhibited dramatically reduced vitamin A levels and significant accumulation of provitamin carotenoids.
- CMO1 deficiency led to impaired lipid homeostasis, characterized by fatty liver and altered serum lipid profiles (elevated unesterified fatty acids).
- CMO1(-/-) mice showed increased susceptibility to high-fat diet-induced metabolic disturbances and elevated expression of adipogenesis markers.
Conclusions:
- CMO1 is the essential enzyme for endogenous vitamin A production from beta-carotene in mammals.
- Carotenoids, via CMO1, play a significant role in regulating overall lipid metabolism, extending beyond their function as vitamin A precursors.
- This study highlights CMO1 as a key target for understanding and potentially treating metabolic disorders linked to carotenoid and vitamin A pathways.
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