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Project description:The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement.
| S-EPMC6628900 | biostudies-literature
Project description:Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species
| PRJNA454673 | ENA
Project description:Key messageHybrid saplings were more reactive to soil water deficit than Japanese and European larch. European larch had hydraulically safer wood and anisohydric behavior, Japanese and hybrid larch showed isohydric strategy.AbstractDeciduous larch species could be an alternative to evergreen conifers in reforestation, but little is known about drought sensitivity of their saplings. The effect of an experimental drought on hydraulics and quantitative wood anatomy was tested on saplings of European larch (EL, Larix decidua), Japanese larch (JL, Larix kaempferi) and their hybrid (HL). Across species, biomass, transpiration rate and relative water content were higher in controls than in drought stressed trees, but transpiration efficiency was lower. JL had the highest transpiration efficiency under drought, and EL the lowest, coinciding with slower growth of EL. Wood of EL formed before drought was hydraulically safer as shown by higher wall/lumen ratio and lower pit cavity area. EL neither had a significant increase in transpiration efficiency nor a reduction in transpiration rate under drought, suggesting that the stomata remained open under soil water deficit. HL saplings were the most reactive to water shortage, indicated by intra-annual density fluctuations and a decrease in relative water content of the sapwood. Significant reduction in transpiration by HL suggested a higher stomatal sensitivity, while the same leaf surface area was maintained and radial growth was still similar to its best parent, the JL. The latter showed a significantly lower leaf surface area under drought than controls. EL, with its hydraulically safer wood, followed an anisohydric behavior, while JL and HL revealed an isohydric strategy. Altogether, our results suggest species dependent acclimations to drought stress, whereby HL followed the strategy of JL rather than that of EL.Supplementary informationThe online version contains supplementary material available at 10.1007/s00468-021-02129-4.
| S-EPMC8550302 | biostudies-literature
Project description:Drought tolerance is a highly complex trait controlled by numerous interconnected pathways with substantial variation within and across plant species. This complexity makes it difficult to distill individual genetic loci underlying tolerance, and to identify core or conserved drought-responsive pathways. Here, we collected drought physiology and gene expression datasets across diverse genotypes of the C4 cereals sorghum and maize and searched for signatures defining water-deficit responses. Differential gene expression identified few overlapping drought-associated genes across sorghum genotypes, but using a predictive modeling approach, we found a shared core drought response across development, genotype, and stress severity. Our model had similar robustness when applied to datasets in maize, reflecting a conserved drought response between sorghum and maize. The top predictors are enriched in functions associated with various abiotic stress-responsive pathways as well as core cellular functions. These conserved drought response genes were less likely to contain deleterious mutations than other gene sets, suggesting that core drought-responsive genes are under evolutionary and functional constraints. Our findings support a broad evolutionary conservation of drought responses in C4 grasses regardless of innate stress tolerance, which could have important implications for developing climate resilient cereals.
| S-EPMC10013860 | biostudies-literature
Project description:In recent decades, per- and polyfluoroalkyl substances (PFASs) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from seven distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFASs, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.
| S-EPMC10385990 | biostudies-literature
Project description:Roux-en-Y gastric bypass (RYGB) is an effective way to lose weight and reverse type 2 diabetes. We profiled the metabolome of 18 obese patients (nine euglycemic and nine diabetics) that underwent RYGB surgery and seven lean subjects. Plasma samples from the obese patients were collected before the surgery and one week and three months after the surgery. We analyzed the metabolome in association to five hormones (Adiponectin, Insulin, Ghrelin, Leptin, and Resistin), four peptide hormones (GIP, Glucagon, GLP1, and PYY), and two cytokines (IL-6 and TNF). PCA showed samples cluster by surgery time and many microbially driven metabolites (indoles in particular) correlated with the three months after the surgery. Network analysis of metabolites revealed a connection between carbohydrate (mannosamine and glucosamine) and glyoxylate and confirms glyoxylate association to diabetes. Only leptin and IL-6 had a significant association with the measured metabolites. Leptin decreased immediately after RYGB (before significant weight loss), whereas IL-6 showed no consistent response to RYGB. Moreover, leptin associated with tryptophan in support of the possible role of leptin in the regulation of serotonin synthesis pathways in the gut. These results suggest a potential link between gastric leptin and microbial-derived metabolites in the context of obesity and diabetes.
| S-EPMC5979615 | biostudies-literature
Project description:Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
| S-EPMC3652229 | biostudies-literature
Project description:ObjectivesRoux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations.DesignWe used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity.ResultsObese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients.ConclusionsThe identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut-brain axis in the control of reward-based eating behaviour.
| S-EPMC4033279 | biostudies-literature
Project description:To investigate changes in neural activation and desire to eat in response to appetitive cues from pre- to postbariatric surgery for obesity.Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure. However, the mechanisms of action in RYGB are not well understood. A significant proportion of the resulting reduction in caloric intake is unaccounted for by the restrictive and malabsorptive mechanisms and is thought to be mediated by neuroendocrine function. Numerous investigations of postsurgical changes in gut peptides have resulted; however, changes in neural activation after RYGB surgery have not been previously investigated.Functional magnetic resonance imaging and verbal rating scales were used to assess brain activation and desire to eat in response to high- and low-calorie food cues in 10 female patients 1-month pre- and post-RYGB surgery.Postsurgical reductions in brain activation were found in key areas within the mesolimbic reward pathway, which were significantly more pronounced in response to food cues that were high (vs. low) in caloric density. These changes mirrored concurrent postsurgical reductions in desire to eat, which were also greater in response to food cues that were high versus low in caloric density (P = 0.007).Findings support the contention that RYGB surgery leads to substantial changes in neural responses to food cues encountered in the environment, provide a potential mechanism for the selective reduction in preferences for high-calorie foods, and suggest partial neural mediation of changes in caloric intake seen after RYGB surgery.
| S-EPMC3128512 | biostudies-literature
Project description:Zinc is an essential nutrient for bacterial growth. Because host cells can restrict pathogen access to zinc as an antimicrobial defense mechanism, intracellular pathogens such as Francisella must sense their environment and acquire zinc in response. In many bacteria, the conserved transcription factor Zur is a key regulator of zinc acquisition. To identify mechanisms of zinc uptake in Francisella novicida U112, transcriptome sequencing of wild-type and putative zur mutant bacteria was performed. Only three genes were confirmed as directly regulated by Zur and zinc limitation by quantitative reverse transcription-PCR. One of these genes, FTN_0879, is predicted to encode a protein with similarity to the zupT family of zinc transporters, which are not typically regulated by Zur. While a putative znuACB operon encoding a high-affinity zinc transporter was identified in U112, expression of this operon was not controlled by Zur or zinc concentration. Disruption of zupT but not znuA in U112 impaired growth under zinc limitation, suggesting that ZupT is the primary mechanism of zinc acquisition under these conditions. In the virulent Francisella tularensis subsp. tularensis Schu S4 strain, zupT is a pseudogene, and attempts to delete znuA were unsuccessful, suggesting that it is essential in this strain. A reverse TetR repression system was used to knock down the expression of znuA in Schu S4, revealing that znuA is required for growth under zinc limitation and contributes to intracellular growth within macrophages. Overall, this work identifies genes necessary for adaptation to zinc limitation and highlights nutritional differences between environmental and virulent Francisella strains.IMPORTANCEFrancisella tularensis is a tier 1 select agent with a high potential for lethality and no approved vaccine. A better understanding of Francisella virulence factors is required for the development of therapeutics. While acquisition of zinc has been shown to be required for the virulence of numerous intracellular pathogens, zinc uptake has not been characterized in Francisella This work characterizes the Zur regulon in F. novicida and identifies two transporters that contribute to bacterial growth under zinc limitation. In addition, these data identify differences in mechanisms of zinc uptake and tolerance to zinc limitation between F. tularensis and F. novicida, highlighting the role of znuA in the growth of Schu S4 under zinc limitation.
| S-EPMC5786701 | biostudies-literature