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Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism
Grzegorz Palczewski1, M Airanthi K Widjaja-Adhi2, Jaume Amengual3
1Departments of Biochemistry School of Medicine, Case Western Reserve University, Cleveland, OH.
Abstract:
Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals.
Insights
This study reveals how carotenoid accumulation impacts mammalian lipid metabolism and energy expenditure. Different carotenoids, like beta-carotene and zeaxanthin, show distinct effects on liver and serum cholesterol levels.
Area of Science:
- Biochemistry
- Mammalian Physiology
- Nutritional Science
Background:
- Carotenoids offer health benefits, but their biological actions and dietary accumulation effects in mammals are poorly understood.
- Rodent models are limited by rapid carotenoid metabolism and apocarotenoid production, hindering research.
- A novel mouse model was developed to overcome these limitations for studying carotenoid effects.
Purpose of the Study:
- To investigate the physiological effects of dietary beta-carotene and zeaxanthin accumulation in mammals.
- To analyze the impact of carotenoids on liver gene expression, lipid metabolism, and energy expenditure.
- To differentiate the biological functions of structurally similar carotenoids.
Main Methods:
- Established a mouse model deficient in carotenoid catabolism and apocarotenoid production.
- Enriched the diet with either beta-carotene or zeaxanthin.
- Utilized genome-wide microarray analysis to assess liver transcriptome changes.
- Performed biochemical analyses to quantify lipid levels and assess whole-body respiration.
Main Results:
- Carotenoid accumulation altered pathways involved in liver lipid metabolism and mitochondrial respiration.
- Beta-carotene increased liver triglycerides and cholesterol; zeaxanthin elevated serum cholesterol.
- Carotenoids were primarily transported in high-density lipoprotein (HDL) particles.
- Carotenoid accumulation influenced whole-body respiration and energy expenditure.
Conclusions:
- Dietary carotenoid accumulation significantly interacts with mammalian lipid metabolism.
- Structurally related carotenoids, beta-carotene and zeaxanthin, exhibit distinct biological functions.
- This research provides crucial insights into carotenoid's role in mammalian physiology and health.
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