81 research outputs found

    Effects of fish oils on ex vivo B-cell responses of obese subjects upon BCR/TLR stimulation: a pilot study

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    The long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) in fish oil have immunomodulatory properties. B cells are a poorly studied target of EPA/DHA in humans. Therefore, in this pilot study, we tested how n-3 LC-PUFAs influence B-cell responses of obese humans. Obese men and women were assigned to consume four 1-g capsules per day of olive oil (OO, n=12), fish oil (FO, n=12) concentrate or high-DHA-FO concentrate (n=10) for 12 weeks in a parallel design. Relative to baseline, FO (n=9) lowered the percentage of circulating memory and plasma B cells, whereas the other supplements had no effect. There were no postintervention differences between the three supplements. Next, ex vivo B-cell cytokines were assayed after stimulation of Toll-like receptors (TLRs) and/or the B-cell receptor (BCR) to determine if the effects of n-3 LC-PUFAs were pathway-dependent. B-cell IL-10 and TNFα secretion was respectively increased with high DHA-FO (n=10), relative to baseline, with respective TLR9 and TLR9 + BCR stimulation. OO (n=12) and FO (n=12) had no influence on B-cell cytokines compared to baseline, and there were no differences in postintervention cytokine levels between treatment groups. Finally, ex vivo antibody levels were assayed with FO (n=7) after TLR9 + BCR stimulation. Compared to baseline, FO lowered IgM but not IgG levels accompanied by select modifications to the plasma lipidome. Altogether, the results suggest that n-3 LC-PUFAs could modulate B-cell activity in humans, which will require further testing in a larger cohort

    Mitochondrial Respiratory Capacity and Content Are Normal in Young Insulin-Resistant Obese Humans

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    Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in humans. Young (∼23 years) insulin-sensitive lean and insulin-resistant obese men and women were studied. Insulin resistance was confirmed through an intravenous glucose tolerance test. Measures of mitochondrial respiratory capacity and content as well as H(2)O(2) emitting potential and the cellular redox environment were performed in permeabilized myofibers and primary myotubes prepared from vastus lateralis muscle biopsy specimens. No differences in mitochondrial respiratory function or content were observed between lean and obese subjects, despite elevations in H(2)O(2) emission rates and reductions in cellular glutathione. These findings were apparent in permeabilized myofibers as well as in primary myotubes. The results suggest that reductions in mitochondrial respiratory capacity and content are not required for the initial manifestation of peripheral insulin resistance

    The Agrodiversity Experiment: three years of data from a multisite study in intensively managed grasslands

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    Intensively managed grasslands are globally prominent ecosystems. We investigated whether experimental increases in plant diversity in intensively managed grassland communities can increase their resource use efficiency. This work consisted of a coordinated, continental-scale 33-site experiment. The core design was 30 plots, representing 15 grassland communities at two seeding densities. The 15 communities were comprised of four monocultures (two grasses and two legumes) and 11 four-species mixtures that varied in the relative abundance of the four species at sowing. There were 1028 plots in the core experiment, with another 572 plots sown for additional treatments. Sites agreed a protocol and employed the same experimental methods with certain plot management factors, such as seeding rates and number of cuts, determined by local practice. The four species used at a site depended on geographical location, but the species were chosen according to four functional traits: a fast-establishing grass, a slow-establishing persistent grass, a fast-establishing legume, and a slow-establishing persistent legume. As the objective was to maximize yield for intensive grassland production, the species chosen were all high-yielding agronomic species. The data set contains species-specific biomass measurements (yield per species and of weeds) for all harvests for up to four years at 33 sites. Samples of harvested vegetation were also analyzed for forage quality at 26 sites. Analyses showed that the yield of the mixtures exceeded that of the average monoculture in >97% of comparisons. Mixture biomass also exceeded that of the best monoculture (transgressive overyielding) at about 60% of sites. There was also a positive relationship between the diversity of the communities and aboveground biomass that was consistent across sites and persisted for three years. Weed invasion in mixtures was very much less than that in monocultures. These data should be of interest to ecologists studying relationships between diversity and ecosystem function and to agronomists interested in sustainable intensification. The large spatial scale of the sites provides opportunity for analyses across spatial (and temporal) scales. The database can also complement existing databases and meta-analyses on biodiversity–ecosystem function relationships in natural communities by focusing on those same relationships within intensively managed agricultural grasslands

    PFKFB3-Mediated Glycolysis Rescues Myopathic Outcomes in the Ischemic Limb

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    Compromised muscle mitochondrial metabolism is a hallmark of peripheral arterial disease, especially in patients with the most severe clinical manifestation — critical limb ischemia (CLI). We asked whether inflexibility in metabolism is critical for the development of myopathy in ischemic limb muscles. Using Polg mtDNA mutator (D257A) mice, we reveal remarkable protection from hind limb ischemia (HLI) due to a unique and beneficial adaptive enhancement of glycolytic metabolism and elevated ischemic muscle PFKFB3. Similar to the relationship between mitochondria from CLI and claudicating patient muscles, BALB/c muscle mitochondria are uniquely dysfunctional after HLI onset as compared with the C57BL/6 (BL6) parental strain. AAV-mediated overexpression of PFKFB3 in BALB/c limb muscles improved muscle contractile function and limb blood flow following HLI. Enrichment analysis of RNA sequencing data on muscle from CLI patients revealed a unique deficit in the glucose metabolism Reactome. Muscles from these patients express lower PFKFB3 protein, and their muscle progenitor cells possess decreased glycolytic flux capacity in vitro. Here, we show supplementary glycolytic flux as sufficient to protect against ischemic myopathy in instances where reduced blood flow–related mitochondrial function is compromised preclinically. Additionally, our data reveal reduced glycolytic flux as a common characteristic of the failing CLI patient limb skeletal muscle
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