The Energetic Metabolism of Societies Part I: Accounting Concepts

Based upon the currently emerging international consensus on how to account for the materials flows of industrialized countries, this article proposes methods to account for the energetic metabolism of societies. It argues that, to fully exploit the potential of the metabolism approach in the context of sustainable development, both energetic and material aspects of societal metabolism have to be taken into account. The article proposes concepts to empirically describe energy input, internal energy transformations, and energy utilization of societies by extending commonly used notions of energy statistics in a way that is compatible with current methods of materials flow analysis. Whereas energy statistics include only the energy used in technical devices for providing heat, light, mechanical work, and data processing, an accounting system for the energetic metabolism of societies should also consider flows of nutritional energy for both livestock and humans. Moreover, in assessing the energy input of a society, all inputs of energy-rich materials (and immaterial forms of energy such as electricity and light) that cross the boundary into the biophysical structures of society should be taken into consideration, regardless of the purpose for which they are eventually used. As a consequence, an energetic metabolism accounting system treats all biomass as energy input, instead of considering only the biomass used for technical energy generation, as energy statistics do. Part II in this set of articles will apply these concepts to different modes of societal organization and explore the significance of energetic metabolism for sustainable development. In particular, it will explore the significance for policies that aim at increasing the contribution of renewable energy, especially biomass.     

Energetic strategies of shrews: ecological constraints and evolutionary implications

Data on various features influencing resource acquisition and allocation of energy in Soricidae are reviewed. The relationships between these features are examined at the three functional levels that constrain the energetic design of shrews: the maintenance of homeostasis (rate of metabolism and temperature regulation), the balancing of the energy budget (e.g. the influence of body mass, activity rate, various energy saving mechanisms and home range size), and the allocation of energy towards reproduction (e.g. the influence of litter size). Two major contradictory energetic designs may be recognized: one rather expensive design that is observed in cold and temperate climates with relatively predictable fluctuations in resource availability (e.g. in Sorex and Neomys ), and another much less expensive design that is observed mainly in warm or unpredictable environments (e.g. in Crocidura, Suncus and Notiosorex). It is speculated that climate and resource availability impose narrow limits on the evolution of these energetic strategies, mainly because of the small thermal inertia and reduced energetic autonomy of shrews.     

Dynamics of the intensity of respiration in early embryogenesis of amphibians

We studied growth and respiration rate during early ontogenesis of the axolotl Ambystoma mexicanum, Bosca's newt Triturus waltlii, the green toad Bufo viridis, and the smooth clawed frog Xenopus laevis. The respiration rate in these amphibian species increases during embryonal and larval development, peaks after transition to active feeding, and decreases at later stages of ontogenesis. The patterns of dynamics of this energy metabolism index in tailed and tailless amphibians have some differences related to their specific development. The changes in respiration rate in the embryos and larvae are correlated with the concentrations of mitochondria.     

Modern evolutional developmental biology: Mechanical and molecular genetic or phenotypic approaches?

Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.     

Ontogeny of the pain

The article gives an overview of developmental aspects of the ontogeny of pain both in experimental models and in children. The whole article is devoted to the ontogenesis in pain perception and the possible influence on it. The role of endogenous opioids on the development of pain and other important substances such as serotonin, nerve growth factor (NGF) and nicotine are mentioned. There are also important differences of the ontogenesis of thermal and mechanical nociceptive stimulation. The physiological and pathophysiological findings are the backgrounds for principles of treatment, taking into account the special status of analgesics during ontogeny. In particular there are mentioned the special effects of endogenous opioids and especially morphine. It describes the role of vitamin D and erythropoietin during the development of pain perception. This article also mentioned the critical developmental periods in relation to the perception of pain. The attention is paid to stress and immunological changes during the ontogeny of pain. Another important role is played by microglia. The work is concluded by some statements about the use of physiological and pathophysiological findings during the treatment of pain in pediatric practice. Codein analgesia is also described because codein starts to be very modern drug with the dependence.     

Postnatal development of amino acid metabolism enzymes in the liver and muscle of 'cafeteria' rats

The effect of feeding a high-energy highly palatable cafeteria diet on the liver and muscle ontogenesis of serine dehydratase, alanine transaminase, glutamine synthetase and adenylate deaminase during postnatal development of the rat has been studied. The results are in agreement with the lower amino acid utilization in cafeteria rats, both adults and during postnatal development. The feeding of excess energy coupled with high-quality protein resulted in changes in the ontogenesis of the studied enzymes that coincide with the development of protein synthesis and overall pup growth even before they had direct access to this rich diet, suggesting that cafeteria feeding already affects the amino acid metabolism of the pup through the dam's milk.     

Metabolic responses to salinity changes in the subantarctic notothenioid teleost <Emphasis Type="Italic">Eleginops maclovinus</Emphasis>

Eleginops maclovinus is an endemic, subantarctic Notothenioidei species. This study examined the influence of different environmental salinities (5, 15, and 45 psu; and 32 psu as a control) on energy metabolism in E. maclovinus over a period of 14 days. Metabolite contents and enzymatic activities related to carbohydrate, amino acid, and lipid metabolisms were evaluated in metabolic (liver) and osmoregulatory (gill and kidney) tissues. At extreme salinities (5 and 45 psu), the liver showed a high consumption of energy reserves, mainly as amino acids and carbohydrates. Carbohydrate metabolism in the gills did not change under different salinities, but increased lactate levels were found, suggesting that this tissue may use lactate as an energy substrate. Amino acid metabolism in the gills decreased at 5 psu but increased at 45 psu, and lipid metabolism increased at 5 and 15 psu during the first days of the trial, indicating a possible use of lipids as energy. Kidney carbohydrate catabolism and amino acid metabolism increased after 14 days at 45 psu, while lipid metabolism did not vary in relation to salinity changes. Together, these results suggest that the liver is most affected by salinity changes, probably due to its role as a supplier of energetic substrates. The gills and kidney, osmoregulatory tissues, maintained their energy metabolism levels with minor modifications. In conclusion, E. maclovinus exhibits metabolic adjustments to adapt to different salinities, showing the best responses in isosmotic environmental salinities.     

Autumn-winter energetics of Holarctic tree squirrels:a review

Similarities in general size, geometry, lifestyle, and environment mean that certain energetic constraints are common and peculiar to Holarctic tree squirrels as a group. Holarctic tree squirrels are relatively small, diurnal mammals which, in association with their food niche, maintain activity throughout the autumn-winter period. Despite this, they exhibit no major morphological or physiological adaptations to minimize energy expenditure at low temperatures; on the contrary, both basal metabolism and conductance are higher than expected on the grounds of physical size. When they are active energy expenditure is therefore strongly influenced by effective ambient temperature for these species when active in their natural autumn-winter environments. Nest use allows near-basal metabolism at most natural ambient temperatures. The balance of economical inactivity against feeding rewards offset by cold exposure must therefore be a crucial aspect of the lifestyle of these squirrels.     

Microglia-Specific Metabolic Changes in Neurodegeneration

The high energetic demand of the brain deems this organ rather sensitive to changes in energy supply. Therefore, even minor alterations in energy metabolism may underlie detrimental disturbances in brain function, contributing to the generation and progression of neurodegenerative diseases. Considerable evidence supports the key role of deficits in cerebral energy metabolism, particularly hypometabolism of glucose and mitochondrial dysfunction, in the pathophysiology of brain disorders. Major breakthroughs in the field of bioenergetics and neurodegeneration have been achieved through the use of in vitro and in vivo models of disease as well as sophisticated neuroimaging techniques in patients, yet these have been mainly focused on neuron and astrocyte function. Remarkably, the subcellular metabolic mechanisms linked to neurodegeneration that operate in other crucial brain cell types such as microglia have remain obscured, although they are beginning to be unraveled. Microglia, the brain-resident immune sentinels, perform a diverse range of functions that require a high-energy expenditure, namely, their role in brain development, maintenance of the neural environment, response to injury and infection, and activation of repair programs. Interestingly, another key mechanism underlying several neurodegenerative diseases is neuroinflammation, which can be associated with chronic microglia activation. Considering that many brain disorders are accompanied by changes in brain energy metabolism and sustained inflammation, and that energy metabolism has a strong influence on the inflammatory responses of microglia, the emerging significance of microglial energy metabolism in neurodegeneration is highlighted in this review.     

The Energetic Metabolism of Societies: Part II: Empirical Examples

Part I of this set of articles proposed methods to account for the energetic metabolism of societies. In this second part, the methods explicated in Part I are used to analyze the energy flows of societies with different "modes of subsistence": hunter-gatherers, a contemporary agricultural society in southeastern Asia, and a contemporary industrial society (Austria). The empirical examples are used to demonstrate differences in the "characteristic metabolism" of different modes of sub-sistence. The energy system of hunter-gatherers can be described as an "uncontrolled solar energy system," based mainly upon harvesting biomass without attending to its reproduction. Hunter-gatherers use only about 0.001% to 0.01% of the net primary production (NPP) of the territory they inhabit. Agricultural societies harness NPP to a much higher extent: Although agriculture often reduces NPP, the amount of biomass that agricultural societies use is much higher (about 20% of potential NPP). Because ecological energy flows are the main source of energy for agricultural societies, NPP strictly limits the energetic metabolism of agricultural societies. Industrial society uses area-independent energy sources (fossil and nuclear energy), which, however, result in new sustainability problems, such as greenhouse gas emissions. By providing methods to account for changes in energy flows, the metabolism approach proves itself to be a useful concept for analyzing society-environment interactions. The article demonstrates the difference between the metabolism approach and conventional energy statistics and discusses the significance of the proposed approach for sustainable development.     

Influence of energetic status on ontogenetic niche shifts: emergence from the redd is linked to metabolic rate in brown trout

Ontogenetic niche shift should occur when the ratio of growth opportunities to mortality risk becomes higher in the subsequent habitat. While most studies have focused on size to understand the timing of these shifts, an endogenous factor like energetic status (interaction between energy available and energy requirements) appears as a natural candidate to integrate and analyze the growth trade-off between habitats. In this study, we measure energetic content and metabolic rate of individual brown trout (Salmo trutta) fry at emergence from gravel to investigate the influence of energetic status on the timing of this critical ontogenetic niche shift. In addition, as offspring energetic status is subject to parental effects, we examine how females could maximize their own fitness by influencing offspring emergence timing. Our results demonstrate that emergence from gravel is influenced by energetic status. Individuals that emerge first have a higher energetic content but deplete it faster because of a higher metabolic rate. We also find that female fecundity is positively related to emergence period duration. Moreover, our results suggest that females may decrease kin competition during the critical period of emergence by influencing the energetic status of offspring, thus, maximizing their own fitness. Our results help elucidate the mechanisms underlying early ontogenetic niche shifts in juvenile fish and suggest reasons why maternal investment can be so variable within populations.     

The tumor suppressor function of mitochondria: Translation into the clinics

Recently, the inevitable metabolic reprogramming experienced by cancer cells as a result of the onset of cellular proliferation has been added to the list of hallmarks of the cancer cell phenotype. Proliferation is bound to the synchronous fluctuation of cycles of an increased glycolysis concurrent with a restrained oxidative phosphorylation. Mitochondria are key players in the metabolic cycling experienced during proliferation because of their essential roles in the transduction of biological energy and in defining the life–death fate of the cell. These two activities are molecularly and functionally integrated and are both targets of commonly altered cancer genes. Moreover, energetic metabolism of the cancer cell also affords a target to develop new therapies because the activity of mitochondria has an unquestionable tumor suppressor function. In this review, we summarize most of these findings paying special attention to the opportunity that translation of energetic metabolism into the clinics could afford for the management of cancer patients. More specifically, we emphasize the role that mitochondrial β-F1-ATPase has as a marker for the prognosis of different cancer patients as well as in predicting the tumor response to therapy.     

Energetic cost of a meal in a frequent feeding lizard

Specific dynamic action (SDA) describes the rise in metabolism following feeding in animals and represents the energetic cost of digesting and assimilating a meal. The overall energetic cost of feeding may depend on whether or not an animal is post-absorptive at the time of feeding. The aim of this study was to compare the energetic cost of SDA due to feeding frequently compared with infrequently in the eastern water skink, Eulamprus quoyii. For similar quantities of food, repeated feeding incurred an energetic cost equal to 8.8% of the metabolizable energy of the meal (25,220 J), while single feeding incurred an energetic cost of 9.4% of the metabolizable energy of the meal (26,072 J). Experimental lizards maintained a rise in (VO2) that was on average 1.8 times greater than the (VO2) of the unfed controls over a 50-h interval as a result of feeding frequently. This prolonged rise in metabolism resulting from frequent feeding does not result in a higher energetic cost of SDA compared with that resulting from infrequent single feeding.     

Thermal variability increases the impact of autumnal warming and drives metabolic depression in an overwintering butterfly

Increases in thermal variability elevate metabolic rate due to Jensen's inequality, and increased metabolic rate decreases the fitness of dormant ectotherms by increasing consumption of stored energy reserves. Theory predicts that ectotherms should respond to increased thermal variability by lowering the thermal sensitivity of metabolism, which will reduce the impact of the warm portion of thermal variability. We examined the thermal sensitivity of metabolic rate of overwintering Erynnis propertius (Lepidoptera: Hesperiidae) larvae from a stable or variable environment reared in the laboratory in a reciprocal common garden design, and used these data to model energy use during the winters of 1973-2010 using meteorological data to predict the energetic outcomes of metabolic compensation and phenological shifts. Larvae that experienced variable temperatures had decreased thermal sensitivity of metabolic rate, and were larger than those reared at stable temperatures, which could partially compensate for the increased energetic demands. Even with depressed thermal sensitivity, the variable environment was more energy-demanding than the stable, with the majority of this demand occurring in autumn. Autumn phenology changes thus had disproportionate influence on energy consumption in variable environments, and variable-reared larvae were most susceptible to overwinter energy drain. Therefore the energetic impacts of the timing of entry into winter dormancy will strongly influence ectotherm fitness in northern temperate environments. We conclude that thermal variability drives the expression of metabolic suppression in this species; that phenological shifts will have a greater impact on ectotherms in variable thermal environments; and that E. propertius will be more sensitive to shifts in phenology in autumn than in spring. This suggests that increases in overwinter thermal variability and/or extended, warm autumns, will negatively impact all non-feeding dormant ectotherms which lack the ability to suppress their overwinter metabolic thermal sensitivity.     

Pluripotent stem cell energy metabolism: an update

Recent studies link changes in energy metabolism with the fate of pluripotent stem cells (PSCs). Safe use of PSC derivatives in regenerative medicine requires an enhanced understanding and control of factors that optimize in vitro reprogramming and differentiation protocols. Relative shifts in metabolism from naïve through “primed” pluripotent states to lineage‐directed differentiation place variable demands on mitochondrial biogenesis and function for cell types with distinct energetic and biosynthetic requirements. In this context, mitochondrial respiration, network dynamics, TCA cycle function, and turnover all have the potential to influence reprogramming and differentiation outcomes. Shifts in cellular metabolism affect enzymes that control epigenetic configuration, which impacts chromatin reorganization and gene expression changes during reprogramming and differentiation. Induced PSCs (iPSCs) may have utility for modeling metabolic diseases caused by mutations in mitochondrial DNA, for which few disease models exist. Here, we explore key features of PSC energy metabolism research in mice and man and the impact this work is starting to have on our understanding of early development, disease modeling, and potential therapeutic applications.     

Cancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin

The multidrug resistance (MDR) phenotype, frequently observed during cancer treatment, is often associated with drug efflux pump activity. However, many other factors are also known to be involved. Cancer cells often rely on aerobic glycolysis for energy production; this is known as the “Warburg effect” and is used as a survival mechanism. Associated to this event, a reverse pH gradient across the cell membrane occurs, leading to cytosol alkalinization and extracellular acidification. In the present study, we investigated the role of different mechanisms involved in MDR, such as altered tumor microenvironment and energetic metabolism. The breast cancer cell line MCF-7, used as model, was exposed to two widely used antitumor drugs, paclitaxel (antimitotic agent) and doxorubicin (alkylating agent). Cancer pH regulation was shown to be crucial for malignant characteristics such as cell migration and drug resistance. Our results showed that a lower extracellular pH induced a higher migratory capacity and higher resistance to the studied chemotherapeutical compounds in MCF-7 cells. Besides the influence of the extracellular pH, the role of the tumor metabolism in the MDR phenotype was also investigated. Pre-treatment with different bioenergetic modulators led to cell ATP depletion and altered lactic acid production and glucose consumption, resulting in increased sensitivity to paclitaxel and doxorubicin. Overall, this study supports the potential use of compounds targeting cell metabolism and tumor microenvironment factors such as pH, as co-adjuvants in conventional chemotherapy.     

Diffusion of energetic compounds through biological membrane: Application of classical MD and COSMOmic approximations

Computational studies of the potential biological impact of several energetic compounds were performed. The most commonly used explosives were considered in the present studies: trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 2,4-dinitroanisole (DNAN), and 5-Nitro-2,4-dihydro-3H-1,2,4-triazol-3-one (NTO). The effect of such factors as ionic strength and presence of DMSO in the water solution on the structure of the membrane were considered using the POPC lipid bilayer as an example. Molecular dynamics (MD) simulations revealed that, even on a short-time scale, the influence of those additives is noticeable, and therefore those factors should always be taken into account. The MD and the COSMOmic approaches were used to elucidate the ability of the energetic compounds to penetrate the living cell. Calculated free energy profiles and partitioning coefficients revealed distributions of the compounds in the lipid bilayer as well as an overall ability to enter the cell. MD in this case provides a better representation of the free energy profile, while the COSMOmic approach works better to predict log(K_lipw) values. The effect of the functional group was observed for the profiles that were obtained using the MD method.     

Energy, quiescence and the cellular basis of animal life spans

Animals are routinely faced with harsh environmental conditions in which insufficient energy is available to grow and reproduce. Many animals adapt to this challenge by entering a dormant, or quiescent state. In some animals, such as the nematode Caenorhabditis elegans, quiescence is coincident with increased stress resistance and longevity. Here we review evidence that the rules of life span extension established in C. elegans may be generally true of most animals. That is, that the rate of animal aging correlates inversely with cellular resistance to physiological stress, particularly oxidative stress, and that stress resistance is co-regulated with the quiescence adaptation (where the latter occurs). We discuss evidence for highly conserved intracellular signalling pathways involved in energy sensing that are sensitive to aspects of mitochondrial energy transduction and can be modulated in response to energetic flux. We provide a broad overview of the current knowledge of the relationships between energy, metabolism and life span.