Energy Turnover Research Articles

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study

Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches. The SAT of AN patients (n=18, body mass index (BMI) 15.3±1.3kg/m2) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (DINCL) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined. The mean MI was 15.7±1.4kg/m2. The DINCL considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low DINCL: 1.3-28.4mm, and Group 2 showed values up to 58.2mm (corresponding to approximately 6kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level. Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.

Using a Multi-compartmental Metabolic Model to Predict Carbon Allocation in Arabidopsis thaliana.

The molecular mechanism of loading/unloading of sucrose into/from the phloem plays an important role in sucrose translocation among plant tissues. Perturbation of this mechanism results in growth phenotypes of a plant. In order to better understand the coupling of sucrose translocation with metabolic processes a multi-compartmental metabolic network of Arabidopsis thaliana was reconstructed and optimized with respect to biomass growth, both in light and in dark conditions. The model can be used to perform flux balance analysis of metabolic fluxes through the central carbon metabolism and catabolic and anabolic pathways. Balances and turnover of energy (ATP/ADP) and redox metabolites (NAD(P)H/NAD(P)) as well as proton concentrations in different compartments can be estimated. Importantly, the model can be used to quantify the translocation of sucrose from source to sink tissues through phloem in association with an integral balance of protons, which in turn is defined by the operational modes of the energy metabolism (light and dark conditions). This chapter describes how a multi-compartmental model to predict carbon allocation is constructed and used.

Energy turnover in mammalian skeletal muscle in contractions mimicking locomotion: effects of stimulus pattern on work, impulse and energetic cost and efficiency.

Active muscle performs various mechanical functions during locomotion: work output during shortening, work absorption when resisting (but not preventing) lengthening, and impulse (force-time integral) whenever there is active force. The energetic costs of these functions are important components in the energy budget during locomotion. We investigated how the pattern of stimulation and movement affects the mechanics and energetics of muscle fibre bundles isolated from wild rabbits (Oryctolagus cuniculus). The fibres were from muscles consisting of mainly fast-twitch, type 2 fibres. Fibre length was held constant (isometric) or a sinusoidal pattern of movement was imposed at a frequency similar to the stride frequency of running wild rabbits. Duty cycle (stimulation duration×movement frequency) and phase (timing of stimulation relative to movement) were varied. Work and impulse were measured as well as energy produced as heat. The sum of net work (work output-work input) and heat was taken as a measure of energetic cost. Maximum work output was produced with a long duty cycle and stimulation starting slightly before shortening, and was produced quite efficiently. However, efficiency was even higher with other stimulation patterns that produced less work. The highest impulse (considerably higher than isometric impulse) was produced when stimulation started while the muscle fibres were being lengthened. High impulse was produced very economically because of the low cost of producing force during lengthening. Thus, locomotion demanding high work, high impulse or economical work output or impulse requires a distinct pattern of stimulation and movement.

Influence of Mouthguards on Physiological Responses in Rugby.

Mouthguards (MGs) are highly recommended in rugby. Airway obstruction and a resulting decrease in power output are potential disadvantages of their usage. The aim of the study was to assess possible limitations of “vented” (MG V ) and custom-made mouthguards (MG C ) on rugby players’ performance. The MG effects were investigated in 13 male first-league rugby players ranging from 18–34 years old. First a lung function test was completed. Then a double incremental treadmill test was performed to measure maximum aerobic performance, ventilation, VO 2 , VCO 2 , heart rate, and lactate. Effects on sprint times (10 and 40 m) and countermovement jumps were also investigated. Peak flow values were significantly decreased with MG V by about 0.9 l/s. Neither ventilatory parameters nor oxygen uptake were affected by either of the mouthguards. Maximum lactate was significantly decreased in both MG types vs. no MG use. The maximum running velocity was similar in all tests. The aerobic energy turnover was moderately increased with the MG C and MG V . No effects were seen on sprint times or jump tests. Although neither type of mouthguard had a significant impact on maximum performance in treadmill running, the anaerobic energy turnover was decreased.

Creatine and pregnancy outcomes, a prospective cohort study in low-risk pregnant women: study protocol

IntroductionThe creatine kinase circuit is central to the regulation of high-energy phosphate metabolism and the maintenance of cellular energy turnover. This circuit is fuelled by creatine, an amino acid derivative...

The covariance between metabolic rate and behaviour varies across behaviours and thermal types: meta-analytic insights.

Energy metabolism has received much attention as a potential driver of repeatable among-individual differences in behaviour (animal personality). Several factors have been hypothesized to mediate this relationship. We performed a systematic review with a meta-analysis of >70 studies comprised of >8000 individuals reporting relationships between measures of maintenance metabolic rates (i.e. basal metabolic rate, resting metabolic rate, and standard metabolic rate) and behaviour. We evaluated support for three hypothesized mediators: (i) type of behaviour, (ii) opportunities for energy re-allocation, and (iii) magnitude of energetic constraints. Relationships between measures of maintenance metabolic rate (MR) and behaviour are predicted to be strongest for behaviours with strong consequences for energy turnover (acquisition or expenditure). Consistent with this, we found that behaviours with known consequences for energy gain (e.g. foraging, dominance, boldness) or expenditure (e.g. maximum sprint speed, sustained running speed, maximum distance travelled, etc.) had strong positive correlations with MR, while behaviours with putatively weak and/or inconsistent associations with net energy gain or loss (e.g. exploration, activity, sociability) were not correlated with MR. Greater opportunities for energy reallocation are predicted to weaken relationships between MR and behaviour by creating alternative pathways to balance energy budgets. We tested this by contrasting relationships between MR and behaviour in ectotherms versus endotherms, as thermoregulation in endotherms creates additional opportunities for energy reallocation compared with ectotherms. As predicted, the relationship between behaviour and MR was stronger in ectotherms compared with endotherms. However, statistical analyses of heterogeneity among effect sizes from different species did not support energy re-allocation as the main driver of these differences. Finally, we tested whether conditions where animals face greater constraints in meeting their energy budgets (e.g. field versus laboratory, breeding versus non-breeding) increased the strength of the relationship between MR and behaviour. We found that the relationship between MR and behaviour was unaffected by either of these modifiers. This meta-analysis provides two key insights. First, we observed positive relationships of similar magnitude between MR and behaviours that bring in net energy, and behaviours that cost net energy. This result is only consistent with a performance energy-management model. Given that the studies included in our meta-analysis represent a wide range of taxa, this suggests that the performance model may be the most common model in general. Second, we found that behaviours with putatively weak or inconsistent consequences for net energy gain or expenditure (exploration, activity, sociability) show no relationship with MR. The lack of relationship between MR and behavioural traits with weak and/or inconsistent consequences for energy turnover provides the first systematic demonstration of the central importance of the ecological function of traits in mediating relationships between MR and behaviour.

NAMPT Inhibitor KPT-9274 Selectively Targets Self-Renewal Capacity in Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a heterogeneous disease that is characterized by an accumulation of neoplastic myeloid precursor cells in the bone marrow. Recently, multiple agents targeting AML associated mutations in FLT3, IDH1 and IDH2 have been developed. However, a majority of AML patients lack these mutations. Therefore, development of a novel therapeutic approach broadly relevant to AML would be attractive. The clonal capacity of AML cells is maintained by leukemic initiating cells (LICs), which possess self-renewal capabilities and are resistant against cytotoxic combination chemotherapy. Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in the generation of NAD+, which is an important enzymatic cofactor and serves as a metabolite required for cellular respiration. LICs show a higher energy turnover rate than normal cells and are heavily reliant on oxidative phosphorylation. This suggests that energy generation processes, such as NAD+ biosynthesis, are critically required in myeloid malignancies. Thus, targeting the regeneration of NAD+ offers an attractive alternative therapeutic strategy in AML. Unlike many targeted therapies that are limited to one genetic subtype of AML, targeting regeneration of NAD+ via NAMPT inhibition could be relevant to a much broader patient population based upon metabolic differences between tumor and normal cells.We show that inhibition of NAMPT using the agent KPT-9274 induces loss of glycolytic and mitochondrial activity, more specifically a depleted total spare reserve capacity (p<0.001), in MV4-11 and THP-1 cell lines. KPT-9274 treatment decreased colony formation in AML patient samples across multiple genotypes (p<0.001) with a minimal decrease in colony formation by normal CD34+ hematopoietic cells. In addition, KPT-9274 treatment of AML cells decreased re-plating capacity, suggesting decreased self-renewal capacity (p=0.031). In contrast to pre-clinical activity observed in AML, there was minimal depletion of absolute counts observed in cell numbers of B, T and NK-lymphocyte treated ex-vivo as measured by flow cytometry, suggesting potent selectivity of KPT-9274. Furthermore, in a PDX mouse model of AML, KPT-9274 treatment significantly reduced disease burden (p<0.001) and prevented leukemic infiltration in spleen, bone marrow, and liver. In addition, KPT-9274 treatment induced differentiation, which is evident by a decrease in blast percentage and an introduction of segmented and band neutrophils in bone marrow differentials. Mice treated with KPT-9274 showed a reduction of bone marrow CD34+/CD38- cells (p<0.001), which are considered the stem cell population within the bulk leukemic cells. Extending our findings, consecutive re-plating of KPT-9274-treated PDX leukemic cells showed a marked decrease in colony formation, indicative of a loss of self-renewal capacity. KPT-9274 in combination with the anthracycline doxorubicin further decreased the infiltration of AML cells in comparison to either treatment alone. Overall, our data show that the NAMPT inhibitor KPT-9274 targets the leukemia initiating cell population, a potential source of resistance to cytotoxic chemotherapy, which is not adequately eradicated by current therapies in most patients. DisclosuresMims:Abbvie Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Baloglu:Karyopharm Therpeutics: Employment. Senapedis:Karyopharm Therapeutics: Employment.

Protein nitration profile of CD3+ lymphocytes from Alzheimer disease patients: Novel hints on immunosenescence and biomarker detection

Alzheimer's disease (AD) is a progressive form of dementia characterized by increased production of amyloid-β plaques and hyperphosphorylated tau protein, mitochondrial dysfunction, elevated oxidative stress, reduced protein clearance, among other. Several studies showed systemic modifications of immune and inflammatory systems due, in part, to decreased levels of CD3+ lymphocytes in peripheral blood in AD. Considering that oxidative stress, both in the brain and in the periphery, can influence the activation and differentiation of T-cells, we investigated the 3-nitrotyrosine (3-NT) proteome of blood T-cells derived from AD patients compared to non-demented (ND) subjects by using a proteomic approach. 3-NT is a formal protein oxidation and index of nitrosative stress. We identified ten proteins showing increasing levels of 3-NT in CD3+ T-cells from AD patients compared with ND subjects. These proteins are involved in energy metabolism, cytoskeletal structure, intracellular signaling, protein folding and turnover, and antioxidant response and provide new insights into the molecular mechanism that impact reduced T-cell differentiation in AD. Our results highlight the role of peripheral oxidative stress in T-cells related to immune-senescence during AD pathology focusing on the specific targets of protein nitration that conceivably can be suitable to further therapies. Further, our data demonstrate common targets of protein nitration between the brain and the periphery, supporting their significance as disease biomarkers.

PO-305 An 8-week, low carbohydrate, high fat, ketogenic diet enhanced exercise capacity through improved ketolysis and lipolysis in mice

PO-305 An 8-week, low carbohydrate, high fat, ketogenic diet enhanced exercise capacity through improved ketolysis and lipolysis in mice

Sustainable regional development policy formation: role of industrial ecology and logistics

The impossibility to define the clear and uniform operational guidelines for the implementation of sustainable development policy globally proves the necessity to consider the regional level as the key in terms of developing and implementing modern models of sustainable development, in particular, eco-industrial parks and circular economy projects. It substantiates the need to develop and use the modern innovative methodological approaches to the formation of the relevant regional policy. The circular economy proceeds from the flow-based understanding of the character of the production, distribution, exchange, and consumption of goods in the socioeconomic system and, consequently, the turnover of resources and energy within this system. It determines the need for complex analysis and regulation of material and energy flows. These issues constitute the scope of research of industrial ecology and, at the same time, logistics. This causes the question of the integration of these disciplines within the system of scientific and methodological support of the processes of formation and implementation of the policy of sustainable region's development that is as yet little investigated. The article studies the theoretical and methodological foundations of the industrial ecology and logistics, such as objects, goals, methodological principles and approaches, methods, organizational forms, etc. On this basis the ontological unity of these disciplines is brought to light: they simultaneously study the different, mutually reinforcing aspects of the industrial system's performance through the accentuation of the flow form of the organization of the movement of resources, information, and energy as an object of regulation in such system. The integration of the environmental vision of material flows of the regional system, as is characteristic of the industrial ecology, with their content, which characterizes the structure of the regional economic system and constitutes the object of the logistics studies, should be considered as the basis for the formation and implementation of the policy aimed to achieve the region's sustainable development goals.

The benefit of being still: energy savings during winter dormancy in fish come from inactivity and the cold, not from metabolic rate depression.

Winter dormancy is used by many animals to survive the cold and food-poor high-latitude winter. Metabolic rate depression, an active downregulation of resting cellular energy turnover and thus standard (resting) metabolic rate (SMR), is a unifying strategy underlying the persistence of organisms in such energy-limited environments, including hibernating endotherms. However, controversy exists about its involvement in winter-dormant aquatic ectotherms. To address this debate, we conducted simultaneous, multi-day measurements of whole-animal oxygen consumption rate (a proxy of metabolic rate) and spontaneous movement in a model winter-dormant marine fish, the cunner (Tautogolabrus adspersus). Winter dormancy in cunner involved a dampened diel rhythm of metabolic rate, such that a low and stable metabolic rate persisted throughout the 24 h day. Based on the thermal sensitivity (Q10) of SMR as well as correlations of metabolic rate and movement, the reductions in metabolic rate were not attributable to metabolic rate depression, but rather to reduced activity under the cold and darkness typical of the winter refuge among substrate. Previous reports of metabolic rate depression in cunner, and possibly other fish species, during winter dormancy were probably confounded by variation in activity. Unlike hibernating endotherms, and excepting the few fish species that overwinter in anoxic waters, winter dormancy in fishes, as exemplified by cunner, need not involve metabolic rate depression. Rather, energy savings come from inactivity combined with passive physico-chemical effects of the cold on SMR, demonstrating that thermal effects on activity can greatly influence temperature-metabolism relationships, and illustrating the benefit of simply being still in energy-limited environments.

The energetics and thermoregulation of water collecting honeybees

Honeybees need water for different purposes, to maintain the osmotic homeostasis in adults as well as to dilute stored honey and prepare liquid food for the brood. Water is also used for cooling of the hive. Foraging in endothermic insects is energy-intensive and the question arises how much energy bees invest in a resource without any metabolically usable energy. We investigated the energy demand of water collecting bees under natural conditions. The thermoregulation and energetic effort was measured simultaneously in a broad range of experimental ambient temperatures (Ta = 12–40 °C). The thorax temperature as well as the energetic turnover showed a great variability. The mean Tthorax was ranging from ~ 35.7 °C at 12 °C to nearly 42.5 °C at 40 °C. The energy turnover calculated from CO2-release was highest at a Ta of 20 °C with about 60 mW and lowest at 40 °C with about 22 mW per bee. The total costs during collection decreased from 10.4 J at 12 °C to 0.5 J at 40 °C. The energetic effort of the water collectors was comparable with that of 0.5 M sucrose foraging bees. Our investigation strongly supports the hypothesis that the bees’ motivational status determines the energetic performance during foraging.

Potential effects of fat mass and fat-free mass on energy intake in different states of energy balance.

Recently models have attempted to integrate the functional relationships of fat mass (FM) and fat-free mass (FFM) with the control of human energy intake (EI). Cross-sectional evidence suggests that at or close to EB, FFM is positively related to hunger and EI, whereas FM either shows a weak negative or no association with ad libitum EI. Further analysis suggests that the effects of FFM and FM on EI may be mediated by resting metabolic rate (RMR). These studies suggest that energy turnover is associated with EI and the largest determinant of energy requirements in most humans is FFM. During chronic positive EBs both FM and FFM expand (but disproportionately so), increasing energy demands. There is little evidence that an expanding FM exerts strong negative feedback on longer term EI. However, during chronic negative EBs FM, FFM and RMR all decrease but appetite increases. Some studies suggest that proportionate loss of FFM during weight loss predicts subsequent weight regain. Taken together these lines of evidence suggest that changes in the size and functional integrity of FFM may influence appetite and EI. Increases in FFM associated with either weight gain or high levels of exercise may 'pull' EI upwards but energy deficits that decrease FFM may exert a distinct drive on appetite. The current paper discusses how FM and FFM relationships influence appetite regulation, and how size, structure and functional integrity of FFM may drive EI in humans (i) at EB (ii) during positive EB and (iii) during negative EB.

A Method to Evaluate Isotopic and Energy Turnover Rates in Larval Culex quinquefasciatus (Diptera: Culicidae) Using Stable Isotope Labeled Compounds.

The goal of this study was to evaluate the use of stable isotope labeled compounds to better understand factors influencing energy turnover in larval Culex quinquefasciatus (Say; Diptera: Culicidae). Three isotope labeled compounds were evaluated in this study, including 15N-labeled potassium nitrate, 13C-labeled glucose, and 13C-labeled leucine. Conditions were first optimized in the laboratory to determine the most appropriate concentration of isotope, as well as the half-life of enrichment. Once optimum conditions were established we used standard equations to predict and determine temperature and density-dependent energy turnover rates. Our results showed that higher concentrations of isotope had an impact on mosquito survivability, overall enrichment, and adult wing length. We predicted the half-life of to be around 0.614 to 0.971 d, and our observed half-lives were determined to be 0.72 to 1.44 d depending on temperature, larval density, and isotope compound. Both density and temperature had a strong influence on isotopic turnover rates in all isotopes evaluated. Our results suggest that stable isotopes can provide a useful tool in understanding how different stress factors influence energy turnover in larval Cx. quinquefasciatus. These data can also help lay a foundation on ways to improve larvicide efficacy under different biotic and abiotic conditions.

Fructose-containing caloric sweeteners as a cause of obesity and metabolic disorders.

Compared with other carbohydrates, fructose-containing caloric sweeteners (sucrose, high-fructose corn syrup, pure fructose and fructose-glucose mixtures) are characterized by: a sweet taste generally associated with a positive hedonic tone; specific intestinal fructose transporters, i.e. GLUT5; a two-step fructose metabolism, consisting of the conversion of fructose carbones into ubiquitous energy substrates in splanchnic organs where fructolytic enzymes are expressed, and secondary delivery of these substrates to extrasplanchnic tissues. Fructose is a dispensable nutrient, yet its energy can be stored very efficiently owing to a rapid induction of intestinal fructose transporters and of splanchnic fructolytic and lipogenic enzymes by dietary fructose-containing caloric sweeteners. In addition, compared with fat or other dietary carbohydrates, fructose may be favored as an energy store because it uses different intestinal absorption mechanisms and different inter-organ trafficking pathways. These specific features make fructose an advantageous energy substrate in wild animals, mainly when consumed before periods of scarcity or high energy turnover such as migrations. These properties of fructose storage are also advantageous to humans who are involved in strenuous sport activities. In subjects with low physical activity, however, these same features of fructose metabolism may have the harmful effect of favoring energy overconsumption. Furthermore, a continuous exposure to high fructose intake associated with a low energy turnover leads to a chronic overproduction of intrahepatic trioses-phosphate production, which is secondarily responsible for the development of hepatic insulin resistance, intrahepatic fat accumulation, and increased blood triglyceride concentrations. In the long term, these effects may contribute to the development of metabolic and cardiovascular diseases.

Melatonin-Stimulated Triacylglycerol Breakdown and Energy Turnover under Salinity Stress Contributes to the Maintenance of Plasma Membrane H+-ATPase Activity and K+/Na+ Homeostasis in Sweet Potato.

Melatonin (MT) is a multifunctional molecule in animals and plants and is involved in defense against salinity stress in various plant species. In this study, MT pretreatment was simultaneously applied to the roots and leaves of sweet potato seedlings [Ipomoea batatas (L.) Lam.], which is an important food and industry crop worldwide, followed by treatment of 150 mM NaCl. The roles of MT in mediating K+/Na+ homeostasis and lipid metabolism in salinized sweet potato were investigated. Exogenous MT enhanced the resistance to NaCl and improved K+/Na+ homeostasis in sweet potato seedlings as indicated by the low reduced K+ content in tissues and low accumulation of Na+ content in the shoot. Electrophysiological experiments revealed that exogenous MT significantly suppressed NaCl-induced K+ efflux in sweet potato roots and mesophyll tissues. Further experiments showed that MT enhanced the plasma membrane (PM) H+–ATPase activity and intracellular adenosine triphosphate (ATP) level in the roots and leaves of salinized sweet potato. Lipidomic profiling revealed that exogenous MT completely prevented salt-induced triacylglycerol (TAG) accumulation in the leaves. In addition, MT upregulated the expression of genes related to TAG breakdown, fatty acid (FA) β-oxidation, and energy turnover. Chemical inhibition of the β-oxidation pathway led to drastic accumulation of lipid droplets in the vegetative tissues of NaCl-stressed sweet potato and simultaneously disrupted the MT-stimulated energy state, PM H+–ATPase activity, and K+/Na+ homeostasis. Results revealed that exogenous MT stimulated TAG breakdown, FA β-oxidation, and energy turnover under salinity conditions, thereby contributing to the maintenance of PM H+–ATPase activity and K+/Na+ homeostasis in sweet potato.

Single-molecule, full-length transcript sequencing provides insight into the extreme metabolism of the ruby-throated hummingbird Archilochus colubris.

BackgroundHummingbirds oxidize ingested nectar sugars directly to fuel foraging but cannot sustain this fuel use during fasting periods, such as during the night or during long-distance migratory flights. Instead, fasting hummingbirds switch to oxidizing stored lipids that are derived from ingested sugars. The hummingbird liver plays a key role in moderating energy homeostasis and this remarkable capacity for fuel switching. Additionally, liver is the principle location of de novo lipogenesis, which can occur at exceptionally high rates, such as during premigratory fattening. Yet understanding how this tissue and whole organism moderates energy turnover is hampered by a lack of information regarding how relevant enzymes differ in sequence, expression, and regulation.FindingsWe generated a de novo transcriptome of the hummingbird liver using PacBio full-length cDNA sequencing (Iso-Seq), yielding 8.6Gb of sequencing data, or 2.6M reads from 4 different size fractions. We analyzed data using the SMRTAnalysis v3.1 Iso-Seq pipeline, then clustered isoforms into gene families to generate de novo gene contigs using Cogent. We performed orthology analysis to identify closely related sequences between our transcriptome and other avian and human gene sets. Finally, we closely examined homology of critical lipid metabolism genes between our transcriptome data and avian and human genomes.ConclusionsWe confirmed high levels of sequence divergence within hummingbird lipogenic enzymes, suggesting a high probability of adaptive divergent function in the hepatic lipogenic pathways. Our results leverage cutting-edge technology and a novel bioinformatics pipeline to provide a first direct look at the transcriptome of this incredible organism.

Baseline glucose level is an individual trait that is negatively associated with lifespan and increases due to adverse environmental conditions during development and adulthood.

High baseline glucose levels are associated with pathologies and shorter lifespan in humans, but little is known about causes and consequences of individual variation in glucose levels in other species. We tested to what extent baseline blood glucose level is a repeatable trait in adult zebra finches, and whether glucose levels were associated with age, manipulated environmental conditions during development (rearing brood size) and adulthood (foraging cost), and lifespan. We found that: (1) repeatability of glucose levels was 30%, both within and between years. (2) Having been reared in a large brood and living with higher foraging costs as adult were independently associated with higher glucose levels. Furthermore, the finding that baseline glucose was low when ambient temperature was high, and foraging costs were low, indicates that glucose is regulated at a lower level when energy turnover is low. (3) Survival probability decreased with increasing baseline glucose. We conclude that baseline glucose is an individual trait negatively associated with survival, and increases due to adverse environmental conditions during development (rearing brood size) and adulthood (foraging cost). Blood glucose may be, therefore, part of the physiological processes linking environmental conditions to lifespan.

Human Mesenchymal Stem Cell Failure to Adapt to Glucose Shortage and Rapidly Use Intracellular Energy Reserves Through Glycolysis Explains Poor Cell Survival After Implantation

Mesenchymal stem cells (MSCs) hold considerable promise in tissue engineering (TE). However, their poor survival when exogenously administered limits their therapeutic potential. Previous studies from our group demonstrated that lack of glucose (glc) (but not of oxygen) is fatal to human MSCs because it serves as a pro-survival and pro-angiogenic molecule for human MSCs (hMSCs) upon transplantation. However, which energy-providing pathways MSCs use to metabolize glc upon transplantation? Are there alternative energetic nutrients to replace glc? And most importantly, do hMSCs possess significant intracellular glc reserves for ensuring their survival upon transplantation? These remain open questions at the forefront of TE based-therapies. In this study, we established for the first time that the in vivo environment experienced by hMSCs is best reflected by near-anoxia (0.1% O2 ) rather than hypoxia (1%-5% O2 ) in vitro. Under these near-anoxia conditions, hMSCs rely almost exclusively on glc through anerobic glycolysis for ATP production and are unable to use either exogenous glutamine, serine, or pyruvate as energy substrates. Most importantly, hMSCs are unable to adapt their metabolism to the lack of exogenous glc, possess a very limited internal stock of glc and virtually no ATP reserves. This lack of downregulation of energy turnover as a function of exogenous glc level results in a rapid depletion of hMSC energy reserves that explains their poor survival rate. These new insights prompt for the development of glc-releasing scaffolds to overcome this roadblock plaguing the field of TE based-therapies. Stem Cells 2018;36:363-376.

AMPK in skeletal muscle function and metabolism.

Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK’s role as an energy sensor is particularly critical in tissues displaying highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives that need to be investigated. Furthermore, we discuss the possible role of AMPK as a therapeutic target as well as different AMPK activators and their potential for future drug development.—Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M.-N., Pehmøller, C., Shum, M., Marette, A., Mounier, R., Treebak, J. T., Wojtaszewski, J. F. P., Viollet, B., Lantier, L. AMPK in skeletal muscle function and metabolism.