Daytime-Dependent Effects of Thiamine on the Thiamine Pool and Pyruvate Dehydrogenase Regulation in the Brain and Heart

Thiamine is a vitamin essential for the function of central metabolic enzymes, of which pyruvate dehydrogenase (PDH) possesses one of the broadest regulations. Diurnal effects of thiamine supplementation on energy metabolism have previously been shown for the rat brain. Here, we report data on the diurnal changes and the effects of thiamine administration to rats on the function of thiamine-dependent enzymes in the cerebral cortex, heart, and liver. The most pronounced diurnal differences were found at the level of cerebral PDH activity. Analysis of PDH phosphorylation in five rat tissues revealed diurnal and thiamine-dependent differences in the cerebral cortex and heart. The expression of tissue-specific PDH kinases PDK3 and PDK4 showed a daytime-dependent response to thiamine administration in the cerebral cortex and heart, respectively. In addition, cardiac PDK4 expression was doubled in the evening, compared to morning. Furthermore, cerebral cortex demonstrated tissue-specific diurnal changes in thiamine diphosphate (ThDP) and monophosphate levels. Elevation of blood, cardiac, and cerebral ThDP was more effective upon the evening thiamine administration. Importantly, only ThDP was elevated in the rat cerebral cortex exclusively after evening thiamine supplementation. Coenzyme role of ThDP and/or other thiamine functions in nerve tissue reduced the existing daytime changes in animal behavior and ECG parameters. The reported data on diurnal regulation of central energy metabolism as well as the diurnal difference in thiamine accumulation in the cerebral cortex, heart, and other tissues are of clinical importance, as high doses of thiamine are used for the treatment of acute thiamine deficiencies and many other mostly neurological diseases in patients.