Dietary protein-to-carbohydrate ratio effects development and metabolism in Drosophila larvae and imago

Background. Nutrition during growth and development affects various traits not only in larvae but also imago including lifespan, reproduction, feeding, metabolism, and stress resistance. In this study, we have tested the hypothesis of whether the dietary protein-to-carbohydrate (P:C) ratio in the developmental diet could be related to subsequent changes in metabolic profile and physiological parameters in Drosophila larvae and imago. Materials and Methods. Drosophila melanogaster Canton-S strain were used in this study. Larvae were fed diets with different P:C ratios. Experimental media were composed of either 2 % or 5 % dry yeast and 0 %, 1 %, or 10 % of sucrose. We tested developmental rate, wet or dry body weight and the levels of certain metabolites inclu­ding glucose, glycogen, triacylglycerides and total lipids. The developmental rate was assessed by counting the number of generated pupae every 6/6/12 hours. For wet or dry weight measurement, 20 larvae or flies were weighed and transferred to plastic vial with a cut bottom. The flies were dried at 60 °C with the subsequent weighing after two days. Another two-day flies cohort were separated by sex and frozen in liquid nitrogen for further biochemical assays. Hemolymph glucose, total lipid concentration, triacyl­glycerides (TAG), body glucose and glycogen contents were determined spectrophotometrically. Results. We found that a low 0.08 P:C ratio in the diet slowed down pupation by ~20 % and decreased body weight in larvae. Hemolymph glucose levels in both larvae and imago were inversely associated with dietary P:C. Larvae developing on a diet with a low P:C ratio displayed a lower level of glycogen pool, but a higher level of lipids. Developmental dietary P:C ratio also influences metabolic traits such as hemolymph glucose, glycogen, TAG and total lipids in male and female imago. A higher total protein intake combined with restriction of sucrose consumption had glucose-lowering and lipids-lowering effects. Conclusions. Our study demonstrated that nutritional conditions during larval development trigger adaptive changes that provide a level of regulation necessary to surpass dietary stress in Drosophila imago

Alternative NADH dehydrogenase extends lifespan and increases resistance to xenobiotics in Drosophila

Mitochondrial alternative NADH dehydrogenase (aNDH) was found to extend lifespan when expressed in the fruit fly. We have found that fruit flies expressing aNDH from Ciona intestinalis (NDX) had 17-71% lifespan prolongation on media with different protein-tocarbohydrate ratios except NDX-expressing males that had 19% shorter lifespan than controls on a high protein diet. NDX-expressing flies were more resistant to organic xenobiotics, 2,4-dichlorophenoxyacetic acid and alloxan, and inorganic toxicant potassium iodate, and partially to sodium molybdate treatments. On the other hand, NDX-expressing flies were more sensitive to catechol and sodium chromate. Enzymatic analysis showed that NDX-expressing males had higher glucose 6-phosphate dehydrogenase activity, whilst both sexes showed increased glutathione S-transferase activity.Peer reviewe

Alternative NADH dehydrogenase extends lifespan and increases resistance to xenobiotics in Drosophila (vol 147, pg 2311, 2020)

Correction to https://doi.org/10.1007/s10522-019-09849-8Peer reviewe

Essential Physiological Differences Characterize Short- and Long-Lived Strains of Drosophila melanogaster

Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signaling pathways, such as insulin/insulin-like growth factor, can regulate life span of individuals within a species by reprogramming cells in response to environmental changes. Here, we use an unbiased approach to identify novel factors that regulate life span in Drosophila melanogaster. We compare the transcriptome and metabolome of two wild-type strains used widely in aging research: short-lived Dahomey and long-lived Oregon R flies. We found that Dahomey flies carry several traits associated with short-lived individuals and species such as increased lipoxidative stress, decreased mitochondrial gene expression, and increased Target of Rapamycin signaling. Dahomey flies also have upregulated octopamine signaling known to stimulate foraging behavior. Accordingly, we present evidence that increased foraging behavior, under laboratory conditions where nutrients are in excess increases damage generation and accelerates aging. In summary, we have identified several new pathways, which influence longevity highlighting the contribution and importance of the genetic component of aging.This work was supported by the European Research Council (260632 - ComplexI&Aging to A.S.); the Academy of Finland (252048 to A.S); the Biotechnology and Biological Sciences Research Council ( BB/M023311/1 to A.S.); the Centre for International Mobility (CIMO) (TM-12- 8391 and TM-13-8919 to N.G.); the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (PI14/00328 to R.P. and PI17/01286 to P.N.); the Autonomous Government of Catalonia (2017SGR696 and SLT002/16/00250 to R.P.); the Ministry of Education and Science of Ukraine (grant number 0117U006426 to O.L.); FEDER funds from the European Union (“A way to build Europe” to R.P.); and the Doctoral Programme in Medicine and Life Sciences of University of Tampere (to T.R). R.S is a Sir Henry Wellcome Postdoctoral Fellow funded by Wellcome (204715/Z/16/Z

Insulin-Like Peptides Regulate Feeding Preference and Metabolism in Drosophila

Fruit flies have eight identified Drosophila insulin-like peptides (DILPs) that are involved in the regulation of carbohydrate concentrations in hemolymph as well as in accumulation of storage metabolites. In the present study, we investigated diet-dependent roles of DILPs encoded by the genes dilp1–5, and dilp7 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 dilp2,3, dilp3, dilp5, and dilp7 showed higher consumption of proteins on high yeast diets. To evaluate metabolic differences between studied lines on different diets we applied response surface methodology. 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. Fruit fly appetite was influenced by dilp3 and dilp7 genes. Our data contribute to the understanding of Drosophila as a model for further studies of metabolic diseases and may serve as a guide for uncovering the evolution of metabolic regulatory pathways

OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

In a few last decades oxidative stress detected in a variety of physiological processes where reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a central role. They are directly involved in oxidation of proteins, lipids and nucleic acids. In certain concentrations they are necessary for cell division, proliferation and apoptosis. Contractile muscle tissue at aerobic conditions form high ROS flow that may modulate a variety of cell functions, for example proliferation. However, slight increase in ROS level provide hormetic effect which may participate in adaptation to heavy weight training resulted in hypertrophy and proliferation of skeletal muscle fibers. This review will discuss ROS types, sites of generation, strategies to increase force production and achieve skeletal muscle hypertrophy

Insulin Signaling in Intestinal Stem and Progenitor Cells as an Important Determinant of Physiological and Metabolic Traits in Drosophila

The insulin–IGF-1 signaling (IIS) pathway is conserved throughout multicellular organisms and regulates many traits, including aging, reproduction, feeding, metabolism, stress resistance, and growth. Here, we present evidence of a survival-sustaining role for IIS in a subset of gut cells in Drosophila melanogaster, namely the intestinal stem cells (ISCs) and progenitor cells. Using RNAi to knockdown the insulin receptor, we found that inhibition of IIS in ISCs statistically shortened the lifespan of experimental flies compared with non-knockdown controls, and also shortened their survival under starvation or malnutrition conditions. These flies also showed decreased reproduction and feeding, and had lower amounts of glycogen and glucose in the body. In addition, increased expression was observed for the Drosophila transcripts for the insulin-like peptides dilp2, dilp5, and dilp6. This may reflect increased insulin signaling in peripheral tissues supported by up-regulation of the target of the brain insulin gene (tobi). In contrast, activation of IIS (via knockdown of the insulin pathway inhibitor PTEN) in intestinal stem and progenitor cells decreased fly resistance to malnutrition, potentially by affecting adipokinetic hormone signaling. Finally, Pten knockdown to enhance IIS also activated JAK–STAT signaling in gut tissue by up-regulation of upd2, upd3, and soc36 genes, as well as genes encoding the EGF receptor ligands spitz and vein. These results clearly demonstrate that manipulating insulin levels may be used to modulate various fly traits, which are important determinants of organismal survival

Lifespan extension and delay of age-related functional decline caused by Rhodiola rosea depends on dietary macronutrient balance

Abstract Background This study was conducted to evaluate the effects of rhizome powder from the herb Rhodiola rosea, a traditional Western Ukraine medicinal adaptogen, on lifespan and age-related physiological functions of the fruit fly Drosophila melanogaster. Results Flies fed food supplemented with 5.0 mg/ml and 10.0 mg/ml of R. rosea rhizome powder had a 14% to 17% higher median lifespan, whereas at 30.0 mg/ml lifespan was decreased by 9% to 12%. The preparation did not decrease fly fecundity.The effect of R. rosea supplement on lifespan was dependent on diet composition. Lifespan extension by 15% to 21% was observed only for diets with protein-to-carbohydrate ratios less than 1. Lifespan extension was also dependent on total concentration of macronutrients. Thus, for the diet with 15% yeast and 15% sucrose there was no lifespan extension, while for the diet with protein-to-carbohydrate ratio 20:1 R. rosea decreased lifespan by about 10%.Flies fed Rhodiola preparation were physically more active, less sensitive to the redox-cycling compound menadione and had a longer time of heat coma onset compared with controls. Positive effects of Rhodiola rhizome on stress resistance and locomotor activity were highest at the ‘middle age’. Conclusions The present data show that long-term food supplementation with R. rosea rhizome not only increases D. melanogaster lifespan, but also delays age-related decline of physical activity and increases stress resistance, what depends on protein-to-carbohydrate ratio of the diet

OXIDIZED LIPIDS DID NOT REDUCE LIFESPAN IN THE FRUIT FLY, Drosophila melanogaster

Aging is often associated with accumulation of oxidative damage in proteins and lipids. However, some studies do not support this view, raising the question of whether high levels of oxidative damage are associated with lifespan. In the current investigation, Drosophila melanogaster flies were kept on diets with 2 or 10% of either glucose or fructose. The lifespan, fecundity, and feeding as well as amounts of protein carbonyls (PC) and lipid peroxides (LOOH), activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), and glutathione reductase activity o