June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Sex matters in eye and brain metabolism: targeted metabolomics reveals tissue-specific sex difference in metabolism in fasted vs. fed state
Author Affiliations & Notes
  • Olivia Roby
    biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Saravanan Meghashr
    biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Rong Xu
    biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Yekai Wang
    biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Jianhai Du
    biochemistry, West Virginia University Eye Institute, Morgantown, West Virginia, United States
    Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, United States
  • Footnotes
    Commercial Relationships   Olivia Roby None; Saravanan Meghashr None; Rong Xu None; Yekai Wang None; Jianhai Du None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4290. doi:
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      Olivia Roby, Saravanan Meghashr, Rong Xu, Yekai Wang, Jianhai Du; Sex matters in eye and brain metabolism: targeted metabolomics reveals tissue-specific sex difference in metabolism in fasted vs. fed state. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4290.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Metabolism plays critical roles in neuronal health and diseases. Sex is an important biological variable, but how sex influences metabolism in the eye and brain remains unclear. This study aims to address the sex difference in metabolites from mouse eye tissues, brain, and plasma in fed and fasted state using targeted metabolomics.

Methods : Three-month-old C57B6/J mice were ad libitum fed or deprived of food for 18 hours. Mouse eye tissues (retina, eyecup, and lens), brain, and plasma were harvested for targeted metabolomics. The steady-state metabolites were analyzed with liquid chromatography mass spectrometry and gas chromatography mass spectrometry. The data were analyzed with both multivariate Partial least squares-discriminant analysis (PLS-DA) and univariate Volcano Plot analysis (P<0.05 and fold change >1.3).

Results : Multivariate PLS-DA separated male and female groups in all tissues under either fed or fasted state in scores plots, demonstrating there is sex difference in the metabolome. Volcano Plot analysis showed that 8-47 metabolites were different between males and females under the fed state. The lens and retina had the largest number of changes but the plasma had the least. However, under the fasted state, the changed metabolites were reduced to 5-28, and the profiles of changed metabolites were mostly different from the fasted group. Intriguingly, ATP was reduced in the fasted eye cup, lens and brain, but its level was unchanged in the fasted retina. These results suggest that different sexes have different metabolic flexibility. Remarkably, the CoA precursor, Pantothenate, was the only metabolite that was significantly increased in all the female tissues. The fasting further increased Pantothenate in the female eye cup and lens. We also found tissue-specific changes between sexes. Hypoxanthine was retina-specific, succinate was eye cup specific, and cystine, ascorbic acid, adenine, UTP and UDP-Glucosamine were specific to the lens.

Conclusions : Sex influences eye and brain metabolism. Different sexes have tissue-specific and metabolic state-specific changes in metabolome. Our findings support that sex should be considered as a biological variable in the design of metabolomics studies.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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