Impact of caloric restriction on oxidative stress and key glycolytic enzymes in the cerebral cortex, liver and kidney of old and middle-aged mice.

Caloric restriction (CR) is proposed as a strategy to prevent age-related alterations like impaired glucose metabolism and intensification of oxidative stress. In this study, we examined effects of aging and CR on the activities of glycolytic enzymes and parameters of oxidative stress in the cerebral cortex, liver, and kidney of middle-aged (9 months old) and old (18 months old) C57BL6/N mice. Control middle-aged and old mice were fed ad libitum (AL groups), whereas age-matched CR groups were subjected to CR (70% of individual ad libitum food intake) for 6 and 12 months, respectively. There were no significant differences in the activities of key glycolytic and antioxidant enzymes and oxidative stress indices between the cortices of middle-aged and old AL mice. The livers and kidneys of old AL mice showed higher activity of glucose-6-phosphate dehydrogenase, an enzyme that produces NADPH in the pentose phosphate pathway, compared to those of middle-aged mice. CR regimen modulated some biochemical parameters in middle-aged but not in old mice. In particular, CR decreased oxidative stress intensity in the liver and kidney but had no effects on those parameters in the cerebral cortex. In the liver, CR led to lower activities of glycolytic enzymes, whereas its effect was the opposite in the kidney. The results suggest that during physiological aging there is no significant intensification of oxidative stress and glycolysis decline in mouse tissues during the transition from middle to old age. The CR regimen has tissue-specific effects and improves the metabolic state of middle-aged mice. This article is part of the Special Issue on "Ukrainian Neuroscience".

Alpha-ketoglutarate partially alleviates effects of high-fat high-fructose diet in mouse muscle.

Consumption of high-calorie diets leads to excessive accumulation of storage lipids in adipose tissue. Metabolic changes occur not only in adipose tissue but in other tissues, too, such as liver, heart, muscle, and brain. This study aimed to explore the effects of high-fat high-fructose diet (HFFD) alone and in the combination with alpha-ketoglutarate (AKG), a well-known cellular metabolite, on energy metabolism in the skeletal muscle of C57BL/6J mice. Five-month-old male mice were divided into four groups - the control one fed a standard diet (10 % kcal fat), HFFD group fed a high-fat high-fructose diet (45 % kcal fat, 15 % kcal fructose), AKG group fed a standard diet with 1 % sodium AKG in drinking water, and HFFD + AKG group fed HFFD and water with 1 % sodium AKG. The dietary regimens lasted 8 weeks. Mice fed HFFD had higher levels of storage triacylglycerides, lower levels of glycogen, and total water-soluble protein, and higher activities of key glycolytic enzymes, namely hexokinase, phosphofructokinase, and pyruvate kinase, as compared with the control group. The results suggest that muscles of HFFD mice may suffer from lipotoxicity. In HFFD + AKG mice, levels of the metabolites and activities of glycolytic enzymes did not differ from the respective values in the control group, except for the activity of pyruvate kinase, which was significantly lower in HFFD + AKG group compared with the control. Thus, metabolic changes in mouse skeletal muscles, caused by HFFD, were alleviated by AKG, indicating a protective role of AKG regarding lipotoxicity.