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150 results for “metabolic phenotype”
Metabolic phenotype mediates the outcome of competitive interactions in a response-surface field experiment
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Data from: Diabetes mellitus and prediabetes on kidney transplant waiting list- prevalence, metabolic phenotyping and risk stratification approach
Background: Despite a significant prognostic impact, little is known about disturbances in glucose metabolism among kidney transplant candidates. We assess the prevalence of diabetes mellitus (DM) and prediabetes on kidney transplant waiting list, its underlying pathophysiology and propose an approach for individual risk stratification. Methods: All patients on active kidney transplant waiting list of a large European university hospital transplant center were metabolically phenotyped. Results: Of 138 patients, 76 (55%) had disturbances in glucose metabolism. 22% of patients had known DM, 3% were newly diagnosed. 30% were detected to have prediabetes. Insulin sensitivity and -secretion indices allowed for identification of underlying pathophysiology and risk factors. Age independently affected insulin secretion, resulting in a relative risk for prediabetes of 2.95 (95%CI 1.38-4.83) with a cut-off at 48 years. Body mass index independently affected insulin sensitivity as a continuous variable. Conclusions: The prevalence of DM or prediabetes on kidney transplant waiting list is as high as 55%, with more than one third of patients previously undiagnosed. Oral glucose tolerance test is mandatory to detect all patients at risk. Metabolic phenotyping allows for differentiation of underlying pathophysiology and provides a basis for early individual risk stratification and specific intervention to improve patient and allograft outcome.
Data from: Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans
The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity.
Data from: Functional traits in red flour beetles: the dispersal phenotype is associated with leg length but not body size nor metabolic rate
Individuals vary in their ability to disperse. Much of this variation can be described by covarying phenotypic traits that are related to dispersal (constituting the 'dispersal phenotype' or 'dispersal syndrome'), but the nature of the associations among these traits is not well understood. Unravelling the associations among traits that potentially constitute the dispersal phenotype provides a foundation for understanding evolutionary trade-offs due to variation in dispersal. Here, we tested five predictions pertaining to the relationships among physiological, morphological and movement traits that are associated with dispersal, using a species with a long history as a laboratory model for studying ecological phenomena, red flour beetles (Tribolium castaneum). We identified a dominant axis of movement ability that describes variation in dispersal-related movement traits. Individuals that scored positively on this axis moved at higher speed, travelled longer distances, had lower movement intermittency and dispersed quicker to a specified area. Relative leg length, but not body size nor routine metabolic rate related positively with movement ability, indicating a likely mechanistic relationship between increased stride length and movement ability. Our data suggest that the dispersal phenotype may be more strongly linked to morphological traits than physiological ones. We demonstrate that associations among many functional traits do not necessarily conform to a priori expectations, and predict that the substantial intraspecific variation in trait values may be important for selection. Movement is a complex behavioural trait, but it has a mechanistic basis in locomotor morphology that warrants further exploration.
Impacts of a high fat diet on the metabolic profile and the phenotype of atrial myocardium in mice
<p>Aims: Obesity, diabetes and metabolic syndromes are risk factors of atrial fibrillation (AF). We tested the hypothesis that metabolic disorders have a direct impact on the atria favoring the formation of the substrate of AF.</p> <p>Methods & Results: Untargeted metabolomic and lipidomic analysis was used to investigate the consequences of a prolonged high fat diet (HFD) on mouse atria. Atrial properties were characterized by measuring mitochondria respiration in saponin-permeabilized trabeculae, by recording action potential with glass microelectrodes in trabeculae and ionic currents in myocytes using the perforated configuration of patch clamp technique and by several immuno-histological and biochemical approaches. After 16 weeks of HFD, obesogenic mice showed a vulnerability to AF. The atrial myocardium acquired an adipogenic and inflammatory phenotypes. Metabolomic and lipidomic analysis revealed a profound transformation of atrial energy metabolism with a predominance of long-chain lipid accumulation and beta-oxidation activation in the obese mice. Mitochondria respiration showed an increased use of palmitoyl-CoA as energy substrate. Action potentials were short duration and sensitive to the K-ATPdependent channel inhibitor, whereas K-ATP current was enhanced in isolated atrial myocytes of obese mouse.</p> <p>Conclusion:<em><strong> </strong></em>HFD transforms energy metabolism, causes fat accumulation, and induces electrical remodeling of the atrial myocardium of mice that become vulnerable to AF.</p> <p>Translational perspective: Understanding the link between metabolic diseases and atrial fibrillation is of major importance. One hypothesis claims that, in addition to shared co-morbidities, metabolic disorders favor the substrate of atrial fibrillation. Here we show that after prolonged high fat diet, the atrial myocardium becomes adipogenic, inflamed and vulnerable to atrial fibrillation. This tissue remodeling appears to result from an unbalance between uptake and oxidation of fatty acid resulting in long-chain lipid storage, activation metabolic-sensitive potassium channel and action potential shortening. Therefore, diet appears to be an important link between metabolic disorders and atrial fibrillation.</p>
Figure 2 from: Alvarado AT, Ybañez-Julca R, Muñoz AM, Tejada-Bechi C, Cerro R, Quiñones LA, Varela N, Alvarado CA, Alvarado E, Bendezú MR, García JA (2021) Frequency of CYP2D6*3 and *4 and metabolizer phenotypes in three mestizo Peruvian populations. Pharmacia 68(4): 891-898. https://doi.org/10.3897/pharmacia.68.e75165
Figure 2 Percentages (%) of poor metabolizers (gPM) extrapolated from the genotype in different populations of the tricontinent and Latin America previously studied and their clinical implication. ##: tricontinental population, **: Latin American population.
Reduction in the metabolic levels due to phenotypic plasticity in the Pyrenean newt, Calotriton asper, during cave colonization
According to theories on cave adaptation, cave organisms are expected to develop a lower metabolic rate compared to surface organisms as an adaptation to food scarcity in the subterranean environments. To test this hypothesis, we compared the oxygen consumption rates of the surface and subterranean populations of a surface-dwelling species, the newt Calotriton asper, occasionally found in caves. In this study, we designed a new experimental setup in which animals with free movement were monitored for several days in a respirometer. First, we measured the metabolic rates of individuals from the surface and subterranean populations, both maintained for eight years in captivity in a natural cave. We then tested individuals from these populations immediately after they were caught and one year later while being maintained in the cave. We found that the surface individuals that acclimated to the cave significantly reduced their oxygen consumption, whereas individuals from the subterranean population maintained in the cave under a light/dark cycle did not significantly modify their metabolic rates. Second, we compared these metabolic rates to those of an obligate subterranean salamander (Proteus anguinus), a surface aquatic Urodel (Ambystoma mexicanum), and a fish species (Gobio occitaniae) as references for surface organisms from different phyla. As predicted, we found differences between the subterranean and surface species, and the metabolic rates of surface and subterranean C. asper populations were between those of the obligate subterranean and surface species. These results suggest that the plasticity of the metabolism observed in surface C. asper was neither directly due to food availability in our experiments nor the light/dark conditions, but due to static temperatures. Moreover, we suggest that this adjustment of the metabolic level at a temperature close to the thermal optimum may further allow individual species to cope with the food limitations of the subterranean environment.
Gestational and Peri-conceptional Exposure to Intra-nasal Instilled Air Pollutants Epigenetically Perturb Metabolic, Placental and Embryonic Phenotypes
<p><strong>Supplementary Figure legends</strong></p> <p> </p> <p><strong>Figure 1: </strong>Gestational study: Bar plots of plasma metabolites</p> <p> </p> <p><strong>Figure 2:</strong> Gestational study: Bar graph depicting gestational day 19 (GD19) maternal (left) and fetal (right) blood glucose concentrations presented as mean ± SEM. Air pollutant exposed group (AP) versus controls (CON), *p < 0.05 AP versus CON.</p> <p> </p> <p><strong>Figure 3: </strong>Gestational study: <strong>(A)</strong> GO term enrichment analysis of expressed genes between the AP group versus the CON group (n=6 each). Significant enrichment of pathways represented as q-values have been presented in a color-coded key. NES = normalized enrichment score. <strong>(B)</strong> Category cnet plot depicting the linkage of genes and biological concepts (hallmark pathways) as a network illustrating which genes are involved in enriched pathways, and genes that may belong to multiple annotation categories.</p> <p><strong>Figure 4: </strong>Gestational study:<strong> (A) </strong>Representative Western blots of various glucose and lipid transporter proteins and TNFα protein, with vinculin serving as an internal loading control, obtained from CON and AP GD19 placentas<strong>. (B) </strong>Bar plot showing densitometric analysis of Western blots of the various glucose and lipid transporters and TNFα (n=8 for each protein in each group). Data are depicted as Mean ± SEM. While trends are seen, statistical significance was not achieved.</p> <p><strong>Figure 5: </strong>Periconceptional study: <strong>(A)</strong> Bar plots demonstrating fasting blood glucose concentrations (left panel), Glucose tolerance tests (GTTs) (middle panel) and the area under the curves (AUCs) for GTTs (right panel) in non-pregnant (NP), pregnant (P), omega-3 diet exposed (P<em>n-3</em>) pregnant C57/BL6 (BL6) and CD1 pregnant mice are shown. <strong>(B)</strong> Bar plots demonstrating basal fed-state blood glucose concentrations (left panel), Insulin tolerance tests (ITTs) (middle panel) and AUCs for ITTs (right panel) in non-pregnant (NP), pregnant (P), omega-3 diet exposed (P<em>n-3</em>) pregnant C57/BL6 (BL6) and CD1 pregnant mice are shown (n=4-6 each). Data are presented as Mean ± SEM. Significance is shown as <sup>#</sup>compared to BL6-NP, *compared to BL6-P, and <sup>!</sup>compared to BL6-Pn-3 at a p< 0.05.</p> <p><strong>Figure 6: </strong>Periconceptional study:<strong> (A) </strong>Representative Western blots demonstrate various GD19 placental glucose and lipid transporter proteins, with vinculin serving as the internal loading control. <strong>(B) </strong>Bar plots show densitometric analysis of the Western blots of the various glucose and lipid transporters (n=8 for each protein in each group). Data are presented as Mean ± SEM.</p> <p><strong>Figure 7</strong>: Periconceptional study: Category cnet plot depicting the linkage of genes and biological concepts (hallmark pathways) as a network illustrating which genes are involved in enriched pathways, and the genes that may belong to multiple annotation categories between <strong>(A)</strong> AP and CON,<strong> (B)</strong> AP-<em>n-3</em> and AP, <strong>(C) </strong>AP-<em>n-3</em> and CON.</p> <p><strong>Figure 8: </strong>Periconceptional study:<strong> (A)</strong> Bar plots showing coverage of the 5’-hydroxymethylation DNA marks and genomic annotations in GD19 placentas from CON, AP, <em>n-3</em> and AP<em>-n-3</em> experimental groups (n=4 each). <strong>(B)</strong> Pie charts showing the distribution and genomic annotation of differentially methylated regions (DMRs) between the AP and CON groups. Upper panel depicts the distribution of DMRs across CpG-islands and associated regions, while the lower panel depicts the distribution of DMRs around different genomic regions. <strong>(C)</strong> Pie charts showing the distribution and genomic annotation of differentially methylated regions (DMRs) between AP<em>-n-3</em> and CON (left panel), <em>n-3</em> versus CON (middle panel) and AP<em>-n-3</em> versus AP (right panel).</p> <p><strong>Figure 9:</strong> Periconceptional study: <strong>(A-D) </strong>Volcano plots demonstrating the DNA methylation profiles of GD19 placentas from <strong>(A)</strong> AP versus CON, <strong>(B)</strong> AP<em>n-3</em> vs CON, <strong>(C)</strong> <em>n-3</em> vs CON, and <strong>(D)</strong> AP-<em>n-3</em> vs AP groups. Red and blue dots represent hypomethylated and hypermethylated loci respectively (n=4 each group). </p> <p> </p> <p> </p> <p> </p> <p> </p>
Phenotypic resistance to pyrethroid associated to metabolic mechanism in Vgsc-L995F resistant-Anopheles gambiae malaria mosquitoes
<p>Pyrethroid resistance selection was performed over 20 generations with <em>Vgsc</em>-L995F <em>Anopheles gambiae</em> Tiassalé strain. <em>Vgsc</em>-L99F-resistant <em>An. gambiae</em> larvae were exposed to a sublethal dose (killing 20% of larvae) of deltamethrin (LS) and adults to PermaNet 2.0 (AS) at a sublethal time (killing 20% of adults) and combining exposure were realized at larvae and adult stages (LAS) and compared to unexposed group (NS). World Health Organization susceptible tube test was performed at each five generation to follow the evolutionary resistance to deltamethrin. The frequency of <em>Vgsc</em>-L995F/S mutation was screened using multiplex TaqMan qPCR method. Then, expression levels of detoxification enzymes associated to pyrethroid resistance, including CYP4G16, CYP6M2, CYP6P1, CYP6P3, CYP6P4, CYP6Z1 and CYP9K1, and glutathione S-transferase GSTe2 were measured.</p>
Investigating the Effect of Short-term Fasting on T Cell Metabolism, Function, and Phenotype in Obesity
ClinicalTrials.gov study NCT05886738. IPD Sharing: Not stated. Countries: 0. Publications: 2.
Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients
ClinicalTrials.gov study NCT03743025. IPD Sharing: NO. Countries: 1. Publications: 0.
Metabolic Phenotypes of Obesity and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus
ClinicalTrials.gov study NCT06591104. IPD Sharing: NO. Countries: 0. Publications: 4.
The "Metabolically-obese Normal-weight" Phenotype and Its Reversal by Calorie Restriction
ClinicalTrials.gov study NCT03239782. IPD Sharing: NO. Countries: 0. Publications: 54.
Effects of Rosiglitazone on the Metabolic Phenotype of Impaired Glucose Tolerance in Youth
ClinicalTrials.gov study NCT00413335. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Metabolic Phenotypes in Childhood Obesity
ClinicalTrials.gov study NCT03014856. IPD Sharing: Not stated. Countries: 0. Publications: 7.
Data from: Comparative analyses of QTLs influencing obesity and metabolic phenotypes in pigs and humans
Open the record for dataset details and reuse information.
Maternal gut microbiota in pregnancy dictates offspring metabolic phenotype
Open the record for dataset details and reuse information.
Data from: Diabetes mellitus and prediabetes on kidney transplant waiting list- prevalence, metabolic phenotyping and risk stratification approach
Open the record for dataset details and reuse information.
Reduction in the metabolic levels due to phenotypic plasticity in the Pyrenean newt, Calotriton asper, during cave colonization
Open the record for dataset details and reuse information.
Data from: Functional traits in red flour beetles: the dispersal phenotype is associated with leg length but not body size nor metabolic rate
Open the record for dataset details and reuse information.
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