263 research outputs found

    Nematode-Induced Changes of Transporter Gene Expression in \u3ci\u3eArabidopsis\u3c/i\u3e Roots

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    Root-knot plant-parasitic nematodes (Meloidogyne spp.) account for much of the damage inflicted to plants by nematodes. The feeding sites of these nematodes consist of “giant” cells, which have characteristics of transfer cells found in other parts of plants. Increased transport activity across the plasma membrane is a hallmark of transfer cells, and giant cells provide nutrition for nematodes; therefore, we initiated a study to identify the transport processes that contribute to the development and function of nematode- induced feeding sites. The study was conducted over a 4-week period, during which time the large changes in the development of giant cells were documented. The Arabidopsis ATH1 GeneChip was used to identify the many transporter genes that were regulated by nematode infestation. Expression of 50 transporter genes from 18 different gene families was significantly changed upon nematode infestation. Sixteen transporter genes were studied in more detail using real-time reverse-transcriptase polymerase chain reaction to determine transcript abundance in nematode- induced galls that contain giant cells and uninfested regions of the root. Certain genes were expressed primarily in galls whereas others were expressed primarily in the uninfested regions of the root, and a third group was expressed evenly throughout the root. Multiple transport processes are regulated and these may play important roles in nematode feeding-site establishment and maintenance

    Proteomic analysis reveals perturbed energy metabolism and elevated oxidative stress in hearts of rats with inborn low aerobic capacity

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    Selection on running capacity has created rat phenotypes of high‐capacity runners (HCRs) that have enhanced cardiac function and low‐capacity runners (LCRs) that exhibit risk factors of metabolic syndrome. We analysed hearts of HCRs and LCRs from generation 22 of selection using DIGE and identified proteins from MS database searches. The running capacity of HCRs was six‐fold greater than LCRs. DIGE resolved 957 spots and proteins were unambiguously identified in 369 spots. Protein expression profiling detected 67 statistically significant ( p <0.05; false discovery rate <10%, calculated using q ‐values) differences between HCRs and LCRs. Hearts of HCR rats exhibited robust increases in the abundance of each enzyme of the ÎČ‐oxidation pathway. In contrast, LCR hearts were characterised by the modulation of enzymes associated with ketone body or amino acid metabolism. LCRs also exhibited enhanced expression of antioxidant enzymes such as catalase and greater phosphorylation of α B‐crystallin at serine 59, which is a common point of convergence in cardiac stress signalling. Thus, proteomic analysis revealed selection on low running capacity is associated with perturbations in cardiac energy metabolism and provided the first evidence that the LCR cardiac proteome is exposed to greater oxidative stress.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86916/1/3369_ftp.pd

    Intrinsic aerobic capacity sets a divide for aging and longevity

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    &lt;p&gt;&lt;b&gt;Rationale:&lt;/b&gt; Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Objectives:&lt;/b&gt; Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Results:&lt;/b&gt; Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO&lt;sub&gt;2max&lt;/sub&gt;), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P&#60;0.001). VO&lt;sub&gt;2max&lt;/sub&gt;, measured across adulthood was a reliable predictor of lifespan (P&#60;0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo&lt;sub&gt;2&lt;/sub&gt;), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.&lt;/p&gt

    Divergent role of nitric oxide in insulin‐stimulated aortic vasorelaxation between low‐ and high‐intrinsic aerobic capacity rats

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    Low‐intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascular dysfunction and impaired vascular reactivity to insulin compared to high capacity running (HCR) rats. Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary conditions, and in vitro thoracic aortic vascular function was assessed. LCR exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal, and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal glucose tolerance test, glucose area under the curve (AUC) was not different but insulin AUC was 2‐fold greater in LCR than HCR. Acetylcholine and insulin‐stimulated aortic vasorelaxation was significantly greater in LCR (65.2 ± 3.8%, and 32.7 ± 4.1%) than HCR (55.0 ± 3.3%, and 16.7 ± 2.8%). Inhibition of nitric oxide synthase (NOS) with L‐NAME entirely abolished insulin‐mediated vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited greater expression of Insulin Receptor protein, lower Endothelin Receptor‐A protein, a down‐regulation of transcripts for markers of immune cell infiltration (CD11C, CD4, and F4/80) and up‐regulation of pro‐atherogenic inflammatory genes (VCAM‐1 and MCP‐1) in the aorta wall. Contrary to our hypothesis, low‐aerobic capacity was associated with enhanced aortic endothelial function and NO‐mediated reactivity to insulin, despite increased adiposity and evidence of whole body insulin resistance.Rats selectively bred for low‐aerobic capacity displayed enhanced aortic endothelial function and nitric oxide‐mediated insulin‐stimulated vasorelaxation, despite increased adiposity and evidence of whole body insulin resistance. The vascular reactivity to insulin in high‐intrinsic aerobic capacity rats was independent of nitric oxide. Our findings demonstrate that endothelial and nitric oxide insulin‐mediated vasomotor function in the rat aorta is not always associated with aerobic capacity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112223/1/phy212459.pd

    Inherently Lean Rats Have Enhanced Activity and Skeletal Muscle Response to Central Melanocortin Receptors

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143765/1/oby22166.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143765/2/oby22166_am.pd

    Rats Genetically Selected for High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin by Upregulation of Hepatic Biliverdin Reductase-A (BVRA) and Suppression of UGT1A1

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    Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome proliferator-activated receptor-α (PPARα), a ligand-induced transcription factor, and the higher bilirubin HCR rats had significantly increased PPARα-target genes Fgf21, Abcd3, and Gys2. These are known to promote liver function and glycogen storage, which we found by Periodic acid–Schiff (PAS) staining that hepatic glycogen content was higher in the HCR versus the LCR. Our results demonstrate that exercise stimulates pathways that raise plasma bilirubin through alterations in hepatic enzymes involved in bilirubin synthesis and metabolism, improving liver function, and glycogen content. These mechanisms may explain the beneficial effects of exercise on plasma bilirubin levels and health in humans

    Precision exercise medicine: understanding exercise response variability

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    There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability. In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability531811411153The consensus meeting that led to the writing of this manuscript was held with the financial support of the Pennington Biomedical Research Foundation, the Pennington Biomedical Research Center Division of Education, the LSU Boyd Professorship and the John W. Barton, Sr. Chair in Genetics and Nutrition. No funding and/or honorarium was provided to any member of the writing group for the production of this manuscrip

    Ovariectomy results in differential shifts in gut microbiota in low versus high aerobic capacity rats

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    The increased risk for cardiometabolic disease with the onset of menopause is widely studied and likely precipitated by the decline in endogenous estradiol (E2), yet the precise mechanisms are unknown. The gut microbiome is involved in estrogen metabolism and has been linked to metabolic disease, suggesting its potential involvement in the postmenopausal phenotype. Furthermore, menopause‐associated risk factors, as well as gut ecology, are altered with exercise. Therefore, we studied microbial changes in an ovariectomized (OVX vs. Sham) rat model of high (HCR) and low (LCR) intrinsic aerobic capacity (n = 8–10/group) in relation to changes in body weight/composition, glucose tolerance, and liver triglycerides (TG). Nine weeks after OVX, HCR rats were moderately protected against regional adipose tissue gain and liver TG accumulation (P < 0.05 for both). Microbial diversity and number of the Bacteroidetes phylum were significantly increased in LCR with OVX, but unchanged in HCR OVX relative to Sham. Plasma short‐chain fatty acids (SCFA), produced by bacteria in the gut and recognized as metabolic signaling molecules, were significantly greater in HCR Sham relative to LCR Sham rats (P = 0.05) and were decreased with OVX in both groups. These results suggest that increased aerobic capacity may be protective against menopause‐associated cardiometabolic risk and that gut ecology, and production of signaling molecules such as SCFA, may contribute to the mediation.We have demonstrated modest protection from the metabolic effects of surgical menopause (ovariectomy, OVX) in rats with increased aerobic capacity (high running capacity, HCR) relative to those with low aerobic capacity (low running capacity, LCR). These results are associated with significant differences in gut microbiota and their products (short chain fatty acids) between the two groups.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113123/1/phy212488.pd
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