Semaniuk U. Regulation of physiological and biochemical traits of Drosophila melanogaster by diet and insulin-like peptides

The dissertation is devoted to the study of the influence of the main components of the fruit fly diet, such as proteins and carbohydrates and knockout of genes encoding insulin-like peptides on the regulation of appetite of D. melanogaster, as well as their influence on cell energy homeostasis via regulation through the regulation of glucose and trehalose, glycogen, and triacylglycerols metabolism; the influence of the parental diet on the metabolic activity and lifespan of the F1 offspring. In the present study, we investigated diet-dependent roles of DILPs encoded by the genes dilp1–7 in the regulation of insect appetite, food choice, accumulation of triglycerides, glycogen, glucose, and trehalose in fruit fly bodies and carbohydrates in hemolymph. We have found that the wild type and the mutant lines demonstrate compensatory feeding for carbohydrates. However, mutants on dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast diets. High nutrient diets led to a moderate increase in concentration of glucose in hemolymph of the wild type flies. Mutations on dilp genes changed this pattern. We have revealed that the dilp2 mutation led to a drop in glycogen levels independently on diet, lack of dilp3 led to dramatic increase in circulating trehalose and glycogen levels, especially at low protein consumption. Lack of dilp5 led to decreased levels of glycogen and triglycerides on all diets, whereas knockout on dilp7 caused increase in glycogen levels and simultaneous decrease in triglyceride levels at low protein consumption. It was also found that amount of carbohydrates in the medium coordinates feeding behavior of Drosophila. The volumes of sugar solutions ingested and amounts of different carbohydrates eaten were measured in fruit fly lines with mutated genes for w1118 flies consumed 20–40 μg of fructose or glucose per day regardless of carbohydrate concentration. This relatively constant amount of consumed carbohydrate was regulated due to satiety-driven decreases in the ingested volume of sugar solution, a so-called “compensatory feeding” strategy. This decrease was not observed for flies fed sucrose solutions. The dilp3 mutant and quadruple mutant dilp1–4 showed no “compensatory feeding” when fed glucose but these two mutants consumed larger amounts of sucrose than the wild type from solutions with carbohydrate concentrations equal to or higher than 4 %. Flies with mutations of dilp2, dilp3, dilp4, dilp5, and dilp6 genes consumed larger amounts of carbohydrate from 4–10 % sucrose solutions as compared to the wild type. Mutations of DILPs affected appetite mainly for sucrose and glucose, but the least for fructose.