Implication of metabolomic profiles to wide thermoneutral zone in Mongolian gerbils (Meriones unguiculatus)

Mongolian gerbils (Meriones unguiculatus) have evolved a wide thermoneutral zone (26.5-38.9 degrees C) and high upper critical temperature, and appear to have a high tolerance for heat exposure. Here, we use a metabolomic approach to measure global metabolite profiles for gerbils between lower (27 degrees C) and upper critical temperatures (38 degrees C) to investigate the role of metabolomic characterization in maintaining basal metabolic rates within a wide thermoneutral zone. We found that in serum and liver, 14 and 19 metabolites were significantly altered, respectively. In the aerobic respiration-related tricarboxylic cycle (TCA), 5 intermediates (isocitric acid, cis-aconitic acid, -ketoglutaric acid, fumaric acid and malic acid) were increased in serum in 38 degrees C animals; however, no such increase was found in the liver. A stable level of hepatic TCA cycle intermediates may be related to the steady state of aerobic respiration at 38 degrees C. Metabolomic results also revealed that acute heat exposure caused increased oxidative stress and low molecular weight antioxidants in Mongolian gerbils. Increased methionine and 2-hydroxybutyrate suggest an accelerated synthesis of glutathione. Increased urate and its precursors, inosine and hypoxanthine, were detected at 38 degrees C. Glucuronate, threonate and oxalate involved in ascorbate synthesis and degradation were increased in serum at 38 degrees C. In conclusion, although dramatic metabolomic variation was found, a stable hepatic TCA cycle may contribute to maintaining a constant basal metabolic rate within a wide thermoneutral zone in Mongolian gerbils.