Dietary alpha-ketoglutarate promotes higher protein and lower triacylglyceride levels and induces oxidative stress in larvae and young adults but not in middle-aged Drosophila melanogaster

Alpha-ketoglutarate (AKG) is involved in multiple metabolic and regulatory pathways. In this work, the effects of AKG-supplemented diets on selected physiological responses and metabolic processes, including metabolism of reactive oxygen species, was assessed in larvae and adult (both 2 and 24 days old) Drosophila melanogaster. Dietary supplementation with AKG resulted in dose-dependent effects on larval development, body composition and antioxidant status of third instar larvae. Larvae and young (2 days post-eclosion) adult females fed on AKG shared similar metabolic changes such as higher total protein levels, lower triacylglyceride levels and higher values for oxidative stress indices, namely lipid peroxides and low molecular mass thiols. The latter indicated the development of oxidative stress which, in turn, may induce adaptive responses that can explain the higher resistance of AKG-fed young females to heat shock and hydrogen peroxide exposure. In contrast to young flies, middle-aged females (24 days) on AKG-containing diet possessed higher total protein, glucose and triacylglyceride levels, whereas oxidative stress parameters were virtually the same as compared with control females of the same age. In parallel, females fed an AKG-supplemented diet showed lower fecundity, higher heat shock resistance but no change in oxidative stress resistance at middle age which in combination with levels of protein, glucose, and triacylglycerides can be considered as potentially beneficial AKG effects for aging organisms. To our best knowledge, this is the first study on age-matched AKG influence on animals' organism which shows that Drosophila may be used as a model for previous quick study in cost-efficient manner age-related AKG effects in mammals and humans.