Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki)

Aim: Insulin-resistant skeletal muscle is characterized by metabolic inflexibility with associated alterations in substrate selection, mediated by peroxisome-proliferator activated receptor δ (PPARδ). Although it is established that PPARδ contributes to the alteration of energy metabolism, it is not clear whether it plays a role in mitochondrial fuel competition. While nutrient overload may impair metabolic flexibility by fuel congestion within mitochondria, in absence of obesity defects at a mitochondrial level have not yet been excluded. We sought to determine whether reduced PPARδ content in insulin-resistant rat skeletal muscle of a non-obese rat model of T2DM (Goto-Kakizaki, GK) ameliorate the inhibitory effect of fatty acid (i.e., palmitoylcarnitine) on mitochondrial carbohydrate oxidization (i.e., pyruvate) in muscle fibers. Methods: Bioenergetic function was characterized in oxidative soleus (S) and glycolytic white gastrocnemius (WG) muscles with measurement of respiration rates in permeabilized fibers in the presence of complex I, II, IV, and fatty acid substrates. Mitochondrial content was measured by citrate synthase (CS) and succinate dehydrogenase activity (SDH). Western blot was used to determine protein expression of PPARδ, PDK isoform 2 and 4. Results: CS and SDH activity, key markers of mitochondrial content, were reduced by ∼10–30% in diabetic vs. control, and the effect was evident in both oxidative and glycolytic muscles. PPARδ (p < 0.01), PDK2 (p < 0.01), and PDK4 (p = 0.06) protein content was reduced in GK animals compared to Wistar rats (N = 6 per group). Ex vivo respiration rates in permeabilized muscle fibers determined in the presence of complex I, II, IV, and fatty acid substrates, suggested unaltered mitochondrial bioenergetic function in T2DM muscle. Respiration in the presence of pyruvate was higher compared to palmitoylcarnitine in both animal groups and fiber types. Moreover, respiration rates in the presence of both palmitoylcarnitine and pyruvate were reduced by 25 ± 6% (S), 37 ± 6% (WG) and 63 ± 6% (S), 57 ± 8% (WG) compared to pyruvate for both controls and GK, respectively. The inhibitory effect of palmitoylcarnitine on respiration was significantly greater in GK than controls (p < 10–3). Conclusion: With competing fuels, the presence of fatty acids diminishes mitochondria ability to utilize carbohydrate derived substrates in insulin-resistant muscle despite reduced PPARδ content

RESCALE: Review and Simulate Climate and Catchment Responses at Burrishoole

The climate of the Burrishoole catchment is projected to change significantly over the present century. Previous research of the catchment identified a scientific gap in knowledge in terms of understanding the implications of present and projected future changes in stream flow, water temperature, pH levels and DO concentrations on fish productivity in the catchment. To address this, a multidisciplinary team of scientists undertook an analysis of both present and likely future climate impacts on the catchment with a view to furthering the understanding of the inter-linkages between climate, climate change, and the freshwater ecosystem. The research findings outlined in the report provide climate change information at the catchment scale to assist catchment stakeholders in integrating climate change considerations into their decision-making processes. The report presents an in-depth assessment of the climate and environmental datasets from the catchment to establish if changes have occurred over the period of record. In order to assess the likely impacts of future changes in climate on the catchment, regional climate projections were developed and subsequently employed to simulate likely responses in stream flow and temperature, DOC and DO for the present century. The projected changes in both the climate and water-quality were then used to provide a basis for assessing impacts on fish growth and survival rates of salmonid and eel species in the catchment. The report provides a useful template for future studies, not just in the Burrishoole catchment but for other ecologically important catchments. The findings from the report are relevant to policy makers at the national scale; catchment managers at the regional scale; and, specifically, to stakeholders in the Burrishoole catchment, in developing adaptive responses to climate change.Funded under the Marine Research Sub-programme of the National Development Plan (2007-’13), as part of the Sea Change Strategy.Funder: Marine Institut

Changes in the variability and periodicity of precipitation in Scotland

This paper analyses the temporal and spatial changes in the amount and variability of rainfall in Scotland. The sequential Mann–Kendall test reveals that total annual precipitation has increased across Scotland since the 1970s with increasing trends in variability beginning between the mid-1960s and the mid-1970s. Whilst temporally consistent increasing trends in precipitation totals prevail in the West, many weather stations in the East have experienced subsequent trend turning points in the following two decades, explaining the larger magnitude of the trends in western Scotland in recent decades. Trend analyses on six measures of rainfall variability indicate an increase in rainfall variability during the period 1961–2000, as measured by the intra-annual variance, the winter to summer precipitation ratio and the annual cumulative sum range, with decreasing trends observed in the number of dry days. Periodicities associated with the North Atlantic Oscillation and the Atlantic Multidecadal Oscillation could explain the observed temporal variability of rainfall

Can bias correction and statistical downscaling methods improve the skill of seasonal precipitation forecasts?

Statistical downscaling methods are popular post-processing tools which are widely used in many sectors to adapt the coarse-resolution biased outputs from global climate simulations to the regional-to-local scale typically required by users. They range from simple and pragmatic Bias Correction (BC) methods, which directly adjust the model outputs of interest (e.g. precipitation) according to the available local observations, to more complex Perfect Prognosis (PP) ones, which indirectly derive local predictions (e.g. precipitation) from appropriate upper-air large-scale model variables (predictors). Statistical downscaling methods have been extensively used and critically assessed in climate change applications; however, their advantages and limitations in seasonal forecasting are not well understood yet. In particular, a key problem in this context is whether they serve to improve the forecast quality/skill of raw model outputs beyond the adjustment of their systematic biases. In this paper we analyze this issue by applying two state-of-the-art BC and two PP methods to downscale precipitation from a multimodel seasonal hindcast in a challenging tropical region, the Philippines. To properly assess the potential added value beyond the reduction of model biases, we consider two validation scores which are not sensitive to changes in the mean (correlation and reliability categories). Our results show that, whereas BC methods maintain or worsen the skill of the raw model forecasts, PP methods can yield significant skill improvement (worsening) in cases for which the large-scale predictor variables considered are better (worse) predicted by the model than precipitation. For instance, PP methods are found to increase (decrease) model reliability in nearly 40% of the stations considered in boreal summer (autumn). Therefore, the choice of a convenient downscaling approach (either BC or PP) depends on the region and the season.This study was partially supported by the SPECS and EUPORIAS projects, funded by the European Commission through the Seventh Framework Programme for Research under grant agreements 308378 and 308291, respectively. JMG acknowledges partial support from the project MULTI-SDM (CGL2015-66583-R, MINECO/FEDER)

Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity. Methods In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n = 11), obese participants without diabetes (n = 12), lean individuals (n = 10) and endurance-trained athletes (n = 12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue. Results Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6 +/- 4.0 and 56.7 +/- 7.2 vs 21.8 +/- 2.5 and 25.1 +/- 4.3 years, p <0.001, respectively) and displayed a higher BMI (32.4 +/- 3.7 and 31.0 +/- 3.7 vs 22.1 +/- 1.8 and 21.0 +/- 1.5 kg/m(2), p <0.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86 +/- 0.79 vs 0.79 +/- 0.51 AU, p = 0.002; and OPA1: 1.55 +/- 0.64 vs 0.76 +/- 0.52 AU, p = 0.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (n = 6). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (p = 0.048) and type 2 diabetes (p = 0.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (r = 0.48, p = 0.0001; r = 0.55, p <0.001 and r = 0.61, p <0.0001, respectively) and insulin sensitivity (r = 0.40, p = 0.008; r = 0.44, p = 0.003 and r = 0.48, p = 0.001, respectively). Conclusions/interpretation Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity

Three weeks of time-restricted eating improves glucose homeostasis in adults with type 2 diabetes but does not improve insulin sensitivity: a randomised crossover trial

Aims/hypothesis Time-restricted eating (TRE) is suggested to improve metabolic health by limiting food intake to a defined time window, thereby prolonging the overnight fast. This prolonged fast is expected to lead to a more pronounced depletion of hepatic glycogen stores overnight and might improve insulin sensitivity due to an increased need to replenish nutrient storage. Previous studies showed beneficial metabolic effects of 6-8 h TRE regimens in healthy, overweight adults under controlled conditions. However, the effects of TRE on glucose homeostasis in individuals with type 2 diabetes are unclear. Here, we extensively investigated the effects of TRE on hepatic glycogen levels and insulin sensitivity in individuals with type 2 diabetes.Methods Fourteen adults with type 2 diabetes (BMI 30.5 +/- 4.2 kg/m(2), HbA(1c) 46.1 +/- 7.2 mmol/mol [6.4 +/- 0.7%]) participated in a 3 week TRE (daily food intake within 10 h) vs control (spreading food intake over >= 14 h) regimen in a randomised, crossover trial design. The study was performed at Maastricht University, the Netherlands. Eligibility criteria included diagnosis of type 2 diabetes, intermediate chronotype and absence of medical conditions that could interfere with the study execution and/or outcome. Randomisation was performed by a study-independent investigator, ensuring that an equal amount of participants started with TRE and CON. Due to the nature of the study, neither volunteers nor investigators were blinded to the study interventions. The quality of the data was checked without knowledge on intervention allocation. Hepatic glycogen levels were assessed with C-13-MRS and insulin sensitivity was assessed using a hyperinsulinaemic-euglycaemic two-step clamp. Furthermore, glucose homeostasis was assessed with 24 h continuous glucose monitoring devices. Secondary outcomes included 24 h energy expenditure and substrate oxidation, hepatic lipid content and skeletal muscle mitochondrial capacity.Results Results are depicted as mean +/- SEM. Hepatic glycogen content was similar between TRE and control condition (0.15 +/- 0.01 vs 0.15 +/- 0.01 AU, p=0.88). Mvalue was not significantly affected by TRE (19.6 +/- 1.8 vs 17.7 +/- 1.8 mu mol kg(-1) min(-1) in TRE vs control, respectively, p=0.10). Hepatic and peripheral insulin sensitivity also remained unaffected by TRE (p=0.67 and p=0.25, respectively). Yet, insulin-induced non-oxidative glucose disposal was increased with TRE (non-oxidative glucose disposal 4.3 +/- 1.1 vs 1.5 +/- 1.7 mu mol kg(-1) min(-1), p=0.04). TRE increased the time spent in the normoglycaemic range (15.1 +/- 0.8 vs 12.2 +/- 1.1 h per day, p=0.01), and decreased fasting glucose (7.6 +/- 0.4 vs 8.6 +/- 0.4 mmol/l, p= 0.03) and 24 h glucose levels (6.8 +/- 0.2 vs 7.6 +/- 0.3 mmol/l, p<0.01). Energy expenditure over 24 h was unaffected; nevertheless, TRE decreased 24 h glucose oxidation (260.2 +/- 7.6 vs 277.8 +/- 10.7 g/day, p=0.04). No adverse events were reported that were related to the interventions.Conclusions/interpretation We show that a 10 h TRE regimen is a feasible, safe and effective means to improve 24 h glucose homeostasis in free-living adults with type 2 diabetes. However, these changes were not accompanied by changes in insulin sensitivity or hepatic glycogen

Seaweeds and their communities in polar regions

Polar seaweeds typically begin to grow in late winter-spring, around the time of sea-ice break up. They can grow under very low light enabling distributions to depths of ≥40 m. Moreover, they are physiologically adapted to low temperatures. Intertidal species exhibit a remarkable stress tolerance against freezing, desiccation and salinity changes. Endemism is much greater in the Antarctic compared to the Arctic species. On rocky shores of the Antarctic Peninsula and of Spitsbergen >80% of the bottom can be covered by seaweeds with standing biomass levels ≥20 kg wet wt m-2. Species richness and biomass declines, however, towards higher latitudes. Seaweeds are the dominant organisms in coastal waters and thus play important roles in benthic food webs and are likely to be of particular importance to benthic detrital food chains. Chemical defenses against herbivores are common in Antarctic, but not in Arctic seaweeds. More research is needed especially to study the effects of global climate changes