Figure 5. The cave and surface fish metabolome highlights differences in antioxidant availability and oxidative metabolism.
To analyze changes in redox metabolism in cave populations, we compared the abundance of potent antioxidants and redox-linked metabolites. Metabolites are plotted as mTIC-normalized peak intensities (A,B,C, error bars indicate 2.5/97.5 percentiles). Asterisks indicate significance at the 0.05 level according to an O-PLS / Bayesian logistic regression (Methods) for Pachón vs surface, Tinaja vs surface, and Pachón vs Tinaja. (A) Ascorbate (vitamin C) is a potent antioxidant and essential nutrient. Vitamin C exists as the reduced form ascorbic acid (AA) and oxidized form dehydroascorbic acid (DHAA), which can interconverted by cellular processes. (B) Glutathione, another antioxidant, is significantly increased in the liver and brain under 30-day fasting. Alpha-ketoglutarate is a tricarboxylic acid cycle (TCA) intermediate that has been linked to longevity in nematodes and mice (Chin et al., 2014; Asadi Shahmirzadi et al., 2020). (C) Nicotinamide is a precursor to NAD+ synthesis via a salvage pathway, and increased in the liver but decreased in other tissues in cavefish. Orotic acid is a metabolite that causes fatty liver disease in rats when added to a chow diet.