Migrating bison engineer the green wave.

Newly emerging plants provide the best forage for herbivores. To exploit this fleeting resource, migrating herbivores align their movements to surf the wave of spring green-up. With new technology to track migrating animals, the Green Wave Hypothesis has steadily gained empirical support across a diversity of migratory taxa. This hypothesis assumes the green wave is controlled by variation in climate, weather, and topography, and its progression dictates the timing, pace, and extent of migrations. However, aggregate grazers that are also capable of engineering grassland ecosystems make some of the world's most impressive migrations, and it is unclear how the green wave determines their movements. Here we show that Yellowstone's bison (Bison bison) do not choreograph their migratory movements to the wave of spring green-up. Instead, bison modify the green wave as they migrate and graze. While most bison surfed during early spring, they eventually slowed and let the green wave pass them by. However, small-scale experiments indicated that feedback from grazing sustained forage quality. Most importantly, a 6-fold decadal shift in bison density revealed that intense grazing caused grasslands to green up faster, more intensely, and for a longer duration. Our finding broadens our understanding of the ways in which animal movements underpin the foraging benefit of migration. The widely accepted Green Wave Hypothesis needs to be revised to include large aggregate grazers that not only move to find forage, but also engineer plant phenology through grazing, thereby shaping their own migratory movements.

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study.

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 ).

Individual variation creates diverse migratory portfolios in native populations of a mountain ungulate.

Ecological theory and empirical studies have demonstrated population-level demographic benefits resulting from a diversity of migratory behaviors with important implications for ecology, conservation, and evolution of migratory organisms. Nevertheless, evaluation of migratory portfolios (i.e., the variation in migratory behaviors across space and time among individuals within populations) has received relatively little attention in migratory ungulates, where research has focused largely on the dichotomous behaviors (e.g., resident and migrant) of partially migratory populations. Using GPS data from 361 female bighorn sheep (Ovis canadensis) across 17 (4 restored, 6 augmented, 7 native) populations in Montana and Wyoming, USA, we (1) characterized migratory portfolios based on behavioral and spatial migratory characteristics and (2) evaluated the relative influence of landscape attributes and management histories on migratory diversity. Native populations, which had been extant on the landscape for many generations, had more diverse migratory portfolios, higher behavioral switching rates, reduced seasonal range fidelity, and broad dispersion of individuals across summer and winter ranges. In contrast, restored populations with an abbreviated history on the landscape were largely non-migratory with a narrow portfolio of migratory behaviors, less behavioral switching, higher fidelity to seasonal ranges, and less dispersion on summer and winter ranges. Augmented populations were more variable and contained characteristics of both native and restored populations. Differences in migratory diversity among populations were associated with management histories (e.g., restored, augmented, or native). Landscape characteristics such as the duration and regularity of green-up, human landscape alterations, topography, and snow gradients were not strongly associated with migratory diversity. We suggest a two-pronged approach to restoring migratory portfolios in ungulates that first develops behavior-specific habitat models and then places individuals with known migratory behaviors into unoccupied areas in an effort to bolster migratory portfolios in restored populations, potentially with synergistic benefits associated with variation among individuals and resulting portfolio effects. Management efforts to restore diverse migratory portfolios may increase the abundance, resilience, and long-term viability of ungulate populations.

Do prey select for vacant hunting domains to minimize a multi-predator threat?

Many ecosystems contain sympatric predator species that hunt in different places and times. We tested whether this provides vacant hunting domains, places and times where and when predators are least active, that prey use to minimize threats from multiple predators simultaneously. We measured how northern Yellowstone elk (Cervus elaphus) responded to wolves (Canis lupus) and cougars (Puma concolor), and found that elk selected for areas outside the high-risk domains of both predators consistent with the vacant domain hypothesis. This enabled elk to avoid one predator without necessarily increasing its exposure to the other. Our results demonstrate how the diel cycle can serve as a key axis of the predator hunting domain that prey exploit to manage predation risk from multiple sources. We argue that a multi-predator, spatiotemporal framework is vital to understand the causes and consequences of prey spatial response to predation risk in environments with more than one predator.

Yield responses of arable crops to liming - An evaluation of relationships between yields and soil pH from a long-term liming experiment.

The management of optimal soil pH is fundamental to sustainable crop production. Understanding the lime requirement for arable crops has developed gradually over the last several decades. The aim of this study was to examine the yield-pH relationship for a range of arable crops to understand their response to liming, based on the Long-Term Liming experiments established in 1962 at Rothamsted Research, UK. The main treatments of four different rates of lime and, therefore, four distinctly different soil pH levels were maintained for 35 years at two sites (Rothamsted and Woburn). The pH ranged from 4.4 to 8.0. The lime response was tested on the following crops: spring barley, spring oats, spring beans, spring lupins, winter lupins, potatoes, linseed, winter oilseed rape, winter triticale and winter wheat. Relative yield (RY) was used for non-linear regression analysis to detect site, year and phosphorus (P) fertiliser effects on the relationship with pH. Liming had a highly significant positive effect on soil pH, but overall there was no consistent increase or decrease in soil extractable P (Olsen) or exchangeable K. There were significant site effects detected for RY for most crops which reflect differences in the two soil types. Spring oats and potatoes had very weak responses to lime within the pH range tested. For spring barley, winter triticale, winter wheat and winter oilseed rape significant effects of P fertiliser on the yield-pH relationship were found, although the nature of effects differed between crops and sites. Findings from the Long-Term Liming experiment are invaluable in improving the fundamental understanding on the yield-pH relationship for important arable crops and this has significant implications on selecting crops for rotations. The pH at 90% RY was calculated for selected crops and the beneficial effect of fertiliser P was detected in significantly reducing the critical pH value.

Creating an intergenerational university hub: Engaging older and younger users in the shaping of space and place.

Intergenerational initiatives in post-secondary settings have demonstrated health and social benefits. However, there is a lack of detail with regard to the process by which such initiatives are conceptualized and the role of older and younger users in their development. Guided by the principles of an Age-Friendly University (AFU) alongside elements from a 'Design Thinking' approach, this project outlines the process undertaken to design a new intergenerational space to promote intergenerational connectivity. An online student survey (n = 504; 72.2% female) and focus groups were conducted with older adults (n = 22; 12 females; aged 70-95), which found similar themes across age groups with respect to: 1) past intergenerational experiences; 2) perceived benefits/challenges of accessing the space, and; 3) activity suggestions. Using these findings, alongside direct stakeholder input, Occupational Therapy students developed programming and design suggestions for the space in question aimed at strengthening interactions across age and ability. Results from this process indicate consulting with older and younger users can circumvent potential challenges and inform the design of campus-based initiatives that can promote intergenerational exchange.

Assessing uncertainty in the burden of hepatitis C virus: Comparison of estimated disease burden and treatment costs in the UK.

Hepatitis C virus (HCV) is a major and growing public health concern. We need to know the expected health burden and treatment cost, and understand uncertainty in those estimates, to inform policymaking and future research. Two models that have been important in informing treatment guidelines and assessments of HCV burden were compared by simulating cohorts of individuals with chronic HCV infection initially aged 20, 35 and 50 years. One model predicts that health losses (measured in quality-adjusted life-years [QALYs]) and treatment costs decrease with increasing initial age of the patients, whilst the other model predicts that below 40 years, costs increase and QALY losses change little with age, and above 40 years, they decline with increasing age. Average per-patient costs differ between the models by up to 38%, depending on the patients' initial age. One model predicts double the total number, and triple the peak annual incidence, of liver transplants compared to the other model. One model predicts 55%-314% more deaths than the other, depending on the patients' initial age. The main sources of difference between the models are estimated progression rates between disease states and rates of health service utilization associated with different disease states and, in particular, the age dependency of these parameters. We conclude that decision-makers need to be aware that uncertainties in the health burden and economic cost of HCV disease have important consequences for predictions of future need for care and cost-effectiveness of interventions to avert HCV transmission, and further quantification is required to inform decisions.

Niche similarities among introduced and native mountain ungulates.

The niche concept provides a strong foundation for theoretical and applied research among a broad range of disciplines. When two ecologically similar species are sympatric, theory predicts they will occupy distinct ecological niches to reduce competition. Capitalizing on the increasing availability of spatial data, we built from single species habitat suitability models to a multispecies evaluation of the niche partitioning hypothesis with sympatric mountain ungulates: native bighorn sheep (BHS; Ovis canadensis) and introduced mountain goats (MTG; Oreamnos americanus) in the northeast Greater Yellowstone Area. We characterized seasonal niches using two-stage resource selection functions with a used-available design and descriptive summaries of the niche attributes associated with used GPS locations. We evaluated seasonal similarity in niche space according to confidence interval overlap of model coefficients and similarity in geographic space by comparing model predicted values with Schoener's D metric. Our sample contained 37,962 summer locations from 53 individuals (BHS = 31, MTG = 22), and 79,984 winter locations from 57 individuals (BHS = 35, MTG = 22). Slope was the most influential niche component for both species and seasons, and showed the strongest evidence of niche partitioning. Bighorn sheep occurred on steeper slopes than mountain goats in summer and mountain goats occurred on steeper slopes in winter. The pattern of differential selection among species was less prevalent for the remaining covariates, indicating similarity in niche space. Model predictions in geographic space showed broad seasonal similarity (summer D = 0.88, winter D = 0.87), as did niche characterizations from used GPS locations. The striking similarities in seasonal niches suggest that introduced mountain goats will continue to increase their spatial overlap with native bighorn. Our results suggest that reducing densities of mountain goats in hunted areas where they are sympatric with bighorn sheep and impeding their expansion may reduce the possibility of competition and disease transfer. Additional studies that specifically investigate partitioning at finer scales and along dietary or temporal niche axes will help to inform an adaptive management approach.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS). The efficacy of CEUS in detecting transplant rejection was tested in a murine model of heart transplants, a standard preclinical model of solid organ transplant. As compared to the syngeneic groups, a progressive decline in MP was demonstrated in the allografts undergoing acute transplant rejection (40%, 64%, and 92% on days 4, 6, and 8 posttransplantation, respectively) and chronic rejection (33%, 33%, and 92% on days 5, 14, and 30 posttransplantation, respectively). Our perfusion studies showed restoration of MP following antirejection therapy, highlighting its potential to help monitor efficacy of antirejection therapy. Our data suggest that early endothelial cell injury and platelet aggregation contributed to the early MP decline observed in the allografts. High-resolution MP mapping may allow for noninvasive detection of heart transplant rejection. The data presented have the potential to help in the development of next-generation imaging approaches to diagnose transplant rejection.

Root morphology and seed and leaf ionomic traits in a Brassica napus L. diversity panel show wide phenotypic variation and are characteristic of crop habit.

BACKGROUND: Mineral nutrient uptake and utilisation by plants are controlled by many traits relating to root morphology, ion transport, sequestration and translocation. The aims of this study were to determine the phenotypic diversity in root morphology and leaf and seed mineral composition of a polyploid crop species, Brassica napus L., and how these traits relate to crop habit. Traits were quantified in a diversity panel of up to 387 genotypes: 163 winter, 127 spring, and seven semiwinter oilseed rape (OSR) habits, 35 swede, 15 winter fodder, and 40 exotic/unspecified habits. Root traits of 14 d old seedlings were measured in a 'pouch and wick' system (n = ~24 replicates per genotype). The mineral composition of 3-6 rosette-stage leaves, and mature seeds, was determined on compost-grown plants from a designed experiment (n = 5) by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Seed size explained a large proportion of the variation in root length. Winter OSR and fodder habits had longer primary and lateral roots than spring OSR habits, with generally lower mineral concentrations. A comparison of the ratios of elements in leaf and seed parts revealed differences in translocation processes between crop habits, including those likely to be associated with crop-selection for OSR seeds with lower sulphur-containing glucosinolates. Combining root, leaf and seed traits in a discriminant analysis provided the most accurate characterisation of crop habit, illustrating the interdependence of plant tissues. CONCLUSIONS: High-throughput morphological and composition phenotyping reveals complex interrelationships between mineral acquisition and accumulation linked to genetic control within and between crop types (habits) in B. napus. Despite its recent genetic ancestry (<10 ky), root morphology, and leaf and seed composition traits could potentially be used in crop improvement, if suitable markers can be identified and if these correspond with suitable agronomy and quality traits.

High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napus L.).

Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a 'pouch and wick' HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR.

Detecting grizzly bear use of ungulate carcasses using global positioning system telemetry and activity data.

Global positioning system (GPS) wildlife collars have revolutionized wildlife research. Studies of predation by free-ranging carnivores have particularly benefited from the application of location clustering algorithms to determine when and where predation events occur. These studies have changed our understanding of large carnivore behavior, but the gains have concentrated on obligate carnivores. Facultative carnivores, such as grizzly/brown bears (Ursus arctos), exhibit a variety of behaviors that can lead to the formation of GPS clusters. We combined clustering techniques with field site investigations of grizzly bear GPS locations (n = 732 site investigations; 2004-2011) to produce 174 GPS clusters where documented behavior was partitioned into five classes (large-biomass carcass, small-biomass carcass, old carcass, non-carcass activity, and resting). We used multinomial logistic regression to predict the probability of clusters belonging to each class. Two cross-validation methods-leaving out individual clusters, or leaving out individual bears-showed that correct prediction of bear visitation to large-biomass carcasses was 78-88 %, whereas the false-positive rate was 18-24 %. As a case study, we applied our predictive model to a GPS data set of 266 bear-years in the Greater Yellowstone Ecosystem (2002-2011) and examined trends in carcass visitation during fall hyperphagia (September-October). We identified 1997 spatial GPS clusters, of which 347 were predicted to be large-biomass carcasses. We used the clustered data to develop a carcass visitation index, which varied annually, but more than doubled during the study period. Our study demonstrates the effectiveness and utility of identifying GPS clusters associated with carcass visitation by a facultative carnivore.

Could a trace mineral deficiency be associated with congenital chondrodystrophy of unknown origin (CCUO) in beef cattle in Australia?

Congenital chondrodystrophy of unknown origin (CCUO) has been reported in beef cattle worldwide. A trace mineral deficiency in pregnant dams has been suggested as causing the deformities seen in CCUO calves. An extended outbreak of CCUO in Australia between 2002 and 2009 provided an opportunity to examine the pattern of trace mineral status in gestating cows and the effect of parenteral trace mineral supplementation on a herd at risk of CCUO calves. A property with a strong history of CCUO was identified from a previous case-control study. A randomly selected sample of multiparous (8 to 10 years old) Angus and Angus cross cows (n = 20) was assigned to control (no injection) or supplement group given three injections at the recommended dose rate of chelated mineral supplement (Mn, Zn, Cu and Se) at 6-week intervals in mid- to late gestation. Liver biopsies were performed to measure liver Mn, Zn, Cu and Fe at each injection time and 1 month post-calving. Pasture samples were also collected for analysis. Supplemented cows had higher liver Cu levels compared to control cows (p < 0.001), but there was no difference between supplement and control cows for liver Zn, Fe or Mn. Liver Cu (p < 0.001), Fe (p < 0.001) and Zn (p < 0.001) fell during gestation and liver Mn increased after calving (p < 0.001). Three cows from the control group and two from the supplement group had liver zinc levels below the normal values at the end of the trial. Two cows from the control group and one from the treatment group gave birth to cows with signs of CCUO including superior brachygnathia. All cows except one from the control group had rough dry coats with excessive dander. The role of trace mineral status in the birth of CCUO calves, especially the role of zinc deficiency, requires further investigation.

Challenges and opportunities for quantifying roots and rhizosphere interactions through imaging and image analysis.

The morphology of roots and root systems influences the efficiency by which plants acquire nutrients and water, anchor themselves and provide stability to the surrounding soil. Plant genotype and the biotic and abiotic environment significantly influence root morphology, growth and ultimately crop yield. The challenge for researchers interested in phenotyping root systems is, therefore, not just to measure roots and link their phenotype to the plant genotype, but also to understand how the growth of roots is influenced by their environment. This review discusses progress in quantifying root system parameters (e.g. in terms of size, shape and dynamics) using imaging and image analysis technologies and also discusses their potential for providing a better understanding of root:soil interactions. Significant progress has been made in image acquisition techniques, however trade-offs exist between sample throughput, sample size, image resolution and information gained. All of these factors impact on downstream image analysis processes. While there have been significant advances in computation power, limitations still exist in statistical processes involved in image analysis. Utilizing and combining different imaging systems, integrating measurements and image analysis where possible, and amalgamating data will allow researchers to gain a better understanding of root:soil interactions.

Continuous, high-resolution biospeckle imaging reveals a discrete zone of activity at the root apex that responds to contact with obstacles.

BACKGROUND AND AIMS: Shining a laser onto biological material produces light speckles termed biospeckles. Patterns of biospeckle activity reflect changes in cell biochemistry, developmental processes and responses to the environment. The aim of this work was to develop methods to investigate the biospeckle activity in roots and to characterize the distribution of its intensity and response to thigmostimuli. METHODS: Biospeckle activity in roots of Zea mays, and also Jatropha curcas and Citrus limonia, was imaged live and in situ using a portable laser and a digital microscope with a spatial resolution of 10 µm per pixel and the ability to capture images every 0.080 s. A procedure incorporating a Fujii algorithm, image restoration using median and Gaussian filters, image segmentation using maximum-entropy threshold methods and the extraction of features using a tracing algorithm followed by spline fitting were developed to obtain quantitative information from images of biospeckle activity. A wavelet transform algorithm was used for spectral decomposition of biospeckle activity and generalized additive models were used to attribute statistical significance to changes in patterns of biospeckle activity. KEY RESULTS: The intensity of biospeckle activity was greatest close to the root apex. Higher frequencies (3-6 Hz) contributed most to the total intensity of biospeckle activity. When a root encountered an obstacle, the intensity of biospeckle activity decreased abruptly throughout the root system. The response became attenuated with repeated thigmostimuli. CONCLUSIONS: The data suggest that at least one component of root biospeckle activity resulted from a biological process, which is located in the zone of cell division and responds to thigmostimuli. However, neither individual cell division events nor root elongation is likely to be responsible for the patterns of biospeckle activity.

Integrating population- and individual-level information in a movement model of Yellowstone bison.

Throughout the world, fragmentation of landscapes by human activities has constrained the opportunity for large herbivores to migrate. Conflict between people and wildlife results when migrating animals transmit disease to livestock, damage property, and threaten human safety. Mitigating this conflict requires understanding the forces that shape migration patterns. Bison Bos bison migrating from Yellowstone National Park into the state of Montana during winter and spring concern ranchers on lands surrounding the park because bison can transmit brucellosis (Brucella abortus) to cattle. Migrations have been constrained, with bison being lethally removed or moved back into the park. We developed a state-space model to support decisions on bison management aimed at mitigating conflict with landowners outside the park. The model integrated recent GPS observations with 22 years (1990-2012) of aerial counts to forecast monthly distributions and identify factors driving migration. Wintering areas were located along decreasing elevation gradients, and bison accumulated in wintering areas prior to moving to areas progressively lower in elevation. Bison movements were affected by time since the onset of snowpack, snowpack magnitude, standing crop, and herd size. Migration pathways were increasingly used over time, suggesting that experience or learning influenced movements. To support adaptive management of Yellowstone bison, we forecast future movements to evaluate alternatives. Our approach of developing models capable of making explicit probabilistic forecasts of large herbivore movements and seasonal distributions is applicable to managing the migratory movements of large herbivores worldwide. These forecasts allow managers to develop and refine strategies in advance, and promote sound decision-making that reduces conflict as migratory animals come into contact with people.

Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding.

AIMS/HYPOTHESIS: While it is well known that diet-induced obesity causes insulin resistance, the precise mechanisms underpinning the initiation of insulin resistance are unclear. To determine factors that may cause insulin resistance, we have performed a detailed time-course study in mice fed a high-fat diet (HFD). METHODS: C57Bl/6 mice were fed chow or an HFD from 3 days to 16 weeks and glucose tolerance and tissue-specific insulin action were determined. Tissue lipid profiles were analysed by mass spectrometry and inflammatory markers were measured in adipose tissue, liver and skeletal muscle. RESULTS: Glucose intolerance developed within 3 days of the HFD and did not deteriorate further in the period to 12 weeks. Whole-body insulin resistance, measured by hyperinsulinaemic-euglycaemic clamp, was detected after 1 week of HFD and was due to hepatic insulin resistance. Adipose tissue was insulin resistant after 1 week, while skeletal muscle displayed insulin resistance at 3 weeks, coinciding with a defect in glucose disposal. Interestingly, no further deterioration in insulin sensitivity was observed in any tissue after this initial defect. Diacylglycerol content was increased in liver and muscle when insulin resistance first developed, while the onset of insulin resistance in adipose tissue was associated with increases in ceramide and sphingomyelin. Adipose tissue inflammation was only detected at 16 weeks of HFD and did not correlate with the induction of insulin resistance. CONCLUSIONS/INTERPRETATION: HFD-induced whole-body insulin resistance is initiated by impaired hepatic insulin action and exacerbated by skeletal muscle insulin resistance and is associated with the accumulation of specific bioactive lipid species.