Mutations in genes cnc or dKeap1 modulate stress resistance and metabolic processes in Drosophila melanogaster.

The transcription factor Nrf2 and its negative regulator Keap1 play important roles in the maintenance of redox homeostasis in animal cells. Nrf2 activates defenses against oxidative stress and xenobiotics. Homologs of Nrf2 and Keap1 are present in Drosophila melanogaster (CncC and dKeap1, respectively). The aim of this study was to explore effects of CncC deficiency (due to mutation in the cnc gene) or enhanced activity (due to mutation in the dKeap1 gene) on redox status and energy metabolism of young adult flies in relation to behavioral traits and resistance to a number of stressors. Deficiency in either CncC or dKeap1 delayed pupation and increased climbing activity and heat stress resistance in 2-day-old adult flies. Males and females of the ∆keap1 line shared some similarities such as elevated antioxidant defense as well as lower triacylglyceride and higher glucose levels. Males of the ∆keap1 line also had a higher activity of hexokinase, whereas ∆keap1 females showed higher glycogen levels and lower values of respiratory control and ATP production than flies of the control line. Mutation of cnc gene in allele cncEY08884 caused by insertion of P{EPgy2} transposon in cnc promotor did not affect significantly the levels of metabolites and redox parameters, and even activated some components of antioxidant defense. These data suggest that the mutation can be hypomorphic as well as CncC protein can be dispensable for adult fruit flies under physiological conditions. In females, CncC mutation led to lower mitochondrial respiration, higher hexokinase activity and higher fecundity as compared with the control line. Either CncC activation or its deficiency affected stress resistance of flies.

High amylose starch consumption induces obesity in Drosophila melanogaster and metformin partially prevents accumulation of storage lipids and shortens lifespan of the insects.

There are very few studies that have directly analyzed the effects of dietary intake of slowly digestible starches on metabolic parameters of animals. The present study examined the effects of slowly digestible starch with high amylose content (referred also as amylose starch) either alone, or in combination with metformin on the development, lifespan, and levels of glucose and storage lipids in the fruit fly Drosophila melanogaster. Consumption of amylose starch in concentrations 0.25-10% did not affect D. melanogaster development, whereas 20% starch delayed pupation and reduced the number of larvae that reached the pupal stage. Starch levels in larval food, but not in adult food, determined levels of triacylglycerides in eight-day-old adult flies. Rearing on diet with 20% starch led to shorter lifespan and a higher content of triacylglycerides in the bodies of adult flies as compared with the same parameters in flies fed on 4% starch diet. Food supplementation with 10mM metformin partly attenuated the negative effects of high starch concentrations on larval pupation and decreased triacylglyceride levels in adult flies fed on 20% starch. Long-term consumption of diets supplemented with metformin and starch decreased lifespan of the insects, compared with the diet supplemented with starch only. The data show that in Drosophila high starch consumption may induce a fat fly phenotype and metformin may partially prevent it.

Risks of obesity and diabetes development in the population of the Ivano-Frankivsk region in Ukraine.

The epidemic of obesity that parallels diabetes mellitus and its complications are diseases of major concern to modern societies. Community-based screening is an effective strategy to identify people at high risk of developing overweight, obesity, prediabetes, diabetes, and related health problems. Here, we present the results of screening the population of four locations in the Ivano-Frankivsk region (Western Ukraine). The study group consisted of 400 adults and 252 children. The measured parameters were: (1) main vital signs - body temperature, resting heart rate, blood pressure; (2) anthropometric indicators - body mass and height, body mass index, waist circumference; and (3) metabolic parameters - fasting capillary blood glucose, total body fat, visceral fat, physical activity level and 10-year risk of developing type 2 diabetes. The study found that 23 % of the adults were overweight and 14.8 % obese. Among children, 9.9 % were overweight and 8.7 % obese. Adult body mass index correlated with visceral fat percentage, systolic/diastolic blood pressure and levels of fasting capillary blood glucose. Adults over 18 years of age had fasting capillary blood glucose ≥5.6 mmol/L (14.3 %), including those with undiagnosed pre-diabetes (13.3 %) and suspected diabetes mellitus (1.0 %). The percentage of visceral body fat in adults was positively associated with the 10-year risk of developing type 2 diabetes.

Acetate but not propionate induces oxidative stress in bakers' yeast Saccharomyces cerevisiae.

The influence of acetic and propionic acids on baker's yeast was investigated in order to expand our understanding of the effect of weak organic acid food preservatives on eukaryotic cells. Both acids decreased yeast survival in a concentration-dependent manner, but with different efficiencies. The acids inhibited the fluorescein efflux from yeast cells. The inhibition constant of fluorescein extrusion from cells treated with acetate was significantly lower in parental strain than in either PDR12 (ABC-transporter Pdr12p) or WAR1 (transcriptional factor of Pdr12p) defective mutants. The constants of inhibition by propionate were virtually the same in all strains used. Yeast exposure to acetate increased the level of oxidized proteins and the activity of antioxidant enzymes, while propionate did not change these parameters. This suggests that various mechanisms underlie the yeast toxicity by acetic and propionic acids. Our studies with mutant cells clearly indicated the involvement of Yap1p transcriptional regulator and de novo protein synthesis in superoxide dismutase up-regulation by acetate. The up-regulation of catalase was Yap1p independent. Yeast pre-incubation with low concentrations of H2O2 caused cellular cross-protection against high concentrations of acetate. The results are discussed from the point of view that acetate induces a prooxidant effect in vivo, whereas propionate does not.