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.