Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

Jacqueline C Lieblein-Boff,Adam D Kennedy,Elizabeth J Johnson,Matthew J Kuchan,Chron-Si Lai,Xuchu Weng

doi:10.1371/journal.pone.0136904

Abstract

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

Highlights

Lutein is a naturally occurring xanthophyll carotenoid found in fruits and vegetables, with green leafy vegetables such as spinach and kale accounting for the most abundant sources in nature [1]
We found that lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine, and these correlations were often in a brain region specific manner
The infant brain samples in this study were previously analyzed for carotenoid content, and lutein concentrations were similar across the frontal cortex, hippocampus, and occipital cortex [17]

Summary

Introduction

Lutein is a naturally occurring xanthophyll carotenoid found in fruits and vegetables, with green leafy vegetables such as spinach and kale accounting for the most abundant sources in nature [1]. It can only be acquired in the body through diet. A closely associated carotenoid, are the only carotenoids that constitute the yellow pigment characteristic of the macula [2]. These carotenoids are important for absorbing high energy blue light and protecting the photoreceptor cell layer from oxidative damage [3,4,5]. Lutein has been implicated in protective roles for other tissues in the body. A high carotenoid diet, including lutein, may reduce the risk of some types of cancer [9]

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Conclusion