Mitochondrial metabolites in tissues as indicators of metabolic alterations during hibernation

The decrease in metabolism is one of mechanisms for hibernating animals to resist hypoxia and oxidative stress. Assuming that the inhibition of mitochondria; respiration in torpor and its activation upon arousal are accompanied by changes in the content of mitochondrial substrates, we estimated the levels of endogenous metabolites of the tricarboxylic acid (TCA) cycle in the liver, brown adipose tissue, and the brain of the arctic ground squirrels as possible indicators of mitochondrial processes. The level of lactate in the same tissues and serum was determined as marker of hypoxia. It was found that the isocitrate (ISC) concentration in all tissues was one order of magnitude higher than that of alpha-ketoglutarate (KGL), while succinate was not detected in any of tissues, indicating the inhibition at the initial stages of the TCA cycle. During the torpor, the concentrations of ISC, KGL and lactate predominantly decreased in tissues. Serum lactate decreased five-fold in torpor and was restored in a temperature-dependent manner with a long period of persistence of stable concentration in the range of body temperature between 12 and 27°C upon arousal. The data obtained indicate the development of metabolic depression rather than hypoxia in these tissues.