Variations In Energy Metabolism Research Articles

Promotion of mature angiogenesis in ischemic stroke by Taohong Siwu decoction through glycolysis activation.

Backgrounds: Mature angiogenesis plays a critical role in improving cerebral ischemia-reperfusion injury (CIRI). Glycolysis serves as the primary energy source for brain microvascular endothelial cells (BMECs), whereas other vascular cells rely on aerobic respiration. Therefore, intercellular variations in energy metabolism could influence mature angiogenesis. Taohong Siwu Decoction (THSWD) has demonstrated efficacy in treating ischemic stroke (IS), yet its potential to promote mature angiogenesis through glycolysis activation remains unclear. Methods: In this study, we established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We assessed neuroprotective effects using neurobehavioral scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin-eosin (HE) staining, and Nissl staining in MCAO/R rats. Additionally, we evaluated mature angiogenesis and glycolysis levels through immunofluorescence, immunohistochemistry, and glycolysis assays. Finally, we investigated THSWD's mechanism in linking glycolysis to mature angiogenesis in OGD/R-induced BMECs. Results: In vivo experiments demonstrated that THSWD effectively mitigated cerebral damage and restored neurological function in MCAO/R rats. THSWD significantly enhanced CD31, Ang1, PDGFB, and PDGFR-β expression levels, likely associated with improved glucose, pyruvate, and ATP levels, along with reduced lactate and lactate/pyruvate ratios. In vitro findings suggested that THSWD may boost the expression of mature angiogenesis factors (VEGFA, Ang1, and PDGFB) by activating glycolysis, increasing glucose uptake and augmenting lactate, pyruvate, and ATP content, thus accelerating mature angiogenesis. Conclusion: THSWD could alleviate CIRI by activating the glycolysis pathway to promote mature angiogenesis. Targeting the glycolysis-mediated mature angiogenesis alongside THSWD therapy holds promise for IS treatment.

Social isolation does not alter the relationship between flexibility in metabolic rate and growth in grass carp (Ctenopharyngodon idella) under changing food availability.

Growth and energy metabolism are highly flexible in fish species in response to food availability, and these two traits depend to some extent on the social rearing environment (e.g., isolated vs. group rearing). Currently, how social rearing environments influence flexibility in metabolic rate of fish and their ecological consequences (e.g., somatic growth) remain largely unknown. Here, we investigated how social isolation (i.e., group-reared vs. isolation-reared) and food availability (i.e., high vs. low) affect metabolic rates, growth and their correlations in a group-living fish, grass carp (Ctenopharyngodon idella), which were subjected to a 4-week growth experiment. The metabolic rates (e.g., standard metabolic rate, SMR; maximum metabolic rate, MMR; aerobic scope, AS = MMR-SMR) and morphology (e.g., body mass and length) of the fish in four treatments were measured at the beginning and end of the growth experiment, and then the growth parameters (e.g., food intake, FI; feeding efficiency, FE; and specific growth rate, SGR) were also obtained. We found that social isolation did impair growth of fish with individuals showing a lower SGR compared to those group-reared fish irrespective of food availability. However, the growth advantage of group-reared fish under two food availabilities did not result from their FIs or FEs. Metabolic rates (i.e., SMR) seemed to decrease in response to social isolation, but increased greater when fish were reared at high food ration. These shifts in metabolic rates were positively linked with individual differences in somatic growth; individuals who increased metabolic rates more grew faster, while those who increased their metabolic rates less or even reduced had a lower growth, but these links were independent on both social isolation and food ration. These results suggested that social isolation can inhibit the growth of individual fish, but not the AS. Flexibility in metabolic rates could confer a growth advantage under changing food availability, but the links between variation in energy metabolism and growth were not altered by social deprivation. Our study demonstrates the importance of metabolic plasticity accounting for inter-individual difference in growth performance under the challenges of changing food resource.

Modelling of energy metabolism and analysis of pH variations in postmortem muscle

A kinetic model structure was developed to describe the major variations in energy metabolism and to gain further understanding of pH changes in postmortem muscle experimentally observed with an in vitro glycolytic system. Comparison with experiments showed that the model could describe the kinetics of major metabolites and pH under varied conditions. Optimized model parameters definitively and consistently showed the observed effects of mitochondria, indicating a desirable level of model complexity. Simulation and analysis of pH variations based on the model suggested that phosphofructokinase activity has the strongest impact on the rate and extent of postmortem pH decline. Postmortem pH is also influenced by rates of ATP hydrolysis and glycolysis, and to a much lesser extent, pH buffering capacity. Other reactions, including those mediated by creatine kinase, adenylate kinase, and AMP deaminase, have minimal effects on postmortem pH decline.

Label-free characterization of ischemic cerebral injury using intravital two-photon excitation fluorescence lifetime imaging microscopy

Characterizing an ischemic brain injury at its early stage is critical to biological research and the clinical diagnosis of cerebral ischemia-related diseases. However, approaches with intravital, label-free, and real-time characterization capabilities are scarce. Two-photon excitation fluorescence lifetime imaging microscopy (FLIM) can detect variations in energy metabolism based on the autofluorescence of reduced nicotinamide adenine dinucleotide (NADH). Using this unique feature, we proposed a novel approach for cerebral ischemia characterization. From investigating cell and animal models, the cerebral NADH fluorescence lifetime was observed to be sensitive to metabolic changes caused by ischemia and consistent with ischemic time. A comparison with standard blood flow imaging and neuronal injury assessment further suggests that, the two-photon FLIM, using NADH as an indicator, can characterize degrees of cerebral ischemia and related injuries, particularly at the early stage. These findings demonstrate that NADH FLIM is promising for providing intravital, label-free, and real-time assessment of cerebral ischemia and ischemic brain injury that will be significant to the study and diagnosis of related diseases.

Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning.

Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP. Male C57BL/6J mice (10–12 weeks old) were randomly subjected to Sham, HP [TAC for 3days (TAC 3d), de-banding the aorta for 4 days (De-TAC 4d), and then re-banding the aorta for 4 weeks (Re-TAC 4W)], and TAC (TAC for 4 weeks without de-banding). Cardiac echocardiography, hemodynamics, and histology were utilized to evaluate cardiac remodeling and function. The mRNA expression levels of fetal genes (ANP and BNP), glucose metabolism-related genes (glut4, pdk4), and fatty acid oxidation-related genes (mcad, pgc1α, mcd, pparα) were quantitated by real-time quantitative PCR. Activation of hypertrophy regulators ERK1/2, a metabolic stress kinase AMP-activated protein kinase (AMPK), and its downstream target acetyl-coA carboxylase (ACC) were explored by western blot. Compared with TAC 4W mice, Re-TAC 4W mice showed less impairment in glucose and fatty acid metabolism, as well as less cardiac hypertrophy and dysfunction. Moreover, no significant difference was found in myocardial hypertrophy, fibrosis, and cardiac function in TAC 3d and De-TAC 4d groups compared with Sham group. However, glut4, pdk4, mcad, pgc1α, mcd, and pparα were all decreased, while AMPK and ACC were activated in TAC 3d and returned to Sham level in De-TAC 4d, suggesting that the change in myocardial energy metabolism in HP mice was earlier than that in cardiac structure and function. Collectively, HP improves energy metabolism and delays cardiac remodeling, highlighting that early metabolic improvements drive a potential beneficial effect on structural and functional restoration in cardiac hypertrophy.

Bisphenol A, bisphenol S and their glucuronidated metabolites modulate glycolysis and functional responses of human neutrophils

Bisphenol A (BPA) and its main substitute, bisphenol S (BPS), are synthetic organic compounds found in various consumer products, in particular food and beverage containers. Numerous reports have shown a link between bisphenol exposure, human contamination and increased health problems. BPA, BPS and their metabolites are detectable in bodily fluids (blood, urine) and were reported to affect immune cells and their responses. Though, the impact of those chemicals on neutrophils, the most abundant leukocytes in the circulation, remains poorly described. Therefore, we examined the effects of BPA, BPS and their monoglucuronide conjugates on neutrophil energy metabolism and anti-microbial functions, mainly phagocytosis, superoxide anion generation and CXCL8/IL-8 chemokine production. We observed that short and prolonged exposures of neutrophils to these chemicals modulate the basal and the bacterium-derived peptide N-formyl-methionyl-leucyl-phenylalanine-induced glycolysis, with BPS causing the most alterations. The variation in energy metabolism was not associated with dysfunctions in cell cytotoxicity, phagocytosis, nor superoxide anion production upon exposure to bisphenols. In contrast, bisphenols significantly reduced the production of CXCL8/IL-8 by neutrophils, an effect found to be greater with the glucuronidated metabolites. Our study highlights that BPA, BPS and their glucuronidated metabolites alter the energy metabolism and certain anti-microbial responses of neutrophils, with possible health implications. Importantly, we found that BPS and the glucuronidated metabolites of BPA and BPS showed higher endocrine-disrupting potential than BPA. More studies on bisphenols, especially the less-documented BPS and bisphenol metabolites, are needed to fully determine their risks, allow better regulation of these compounds, and restrict their extensive usage.

Variation in energy metabolism arising from the effect of the tumor microenvironment on cell biological behaviors of bladder cancer cells and endothelial cells.

Tumor energy metabolism and angiogenesis play significant roles in tumor genesis and development, while the effect of the tumor microenvironment (TME), which tumors rely on, is always ignored. In this research, we cocultured bladder cancer (BC) T24 cells with tumor-associated human umbilical vein endothelial cells (HUVECs) under normoxic and hypoxic conditions and detected proliferation, migration, oxidative phosphorylation (OXPHOS) and glycolysis to reveal the energy metabolism characteristics and their effect on cell biological behaviors (CBBs) in the TME. Compared with single-cultured cells, both cocultured T24 cells and HUVECs showed poor proliferation and migration in hypoxic environment, and OXPHOS was activated in cocultured T24 cells but weakened in cocultured HUVECs. However, in normoxic environment, cocultured T24 cells grew much faster while cocultured HUVECs grew slower compared with single-cultured cells. Additionally, glycolysis played a crucial role in energy metabolism and was inhibited in cocultured T24 cells but activated in cocultured HUVECs. In normoxic TME, OXPHOS take main responsibility of energy metabolism. T24 cells exhibited increased proliferation and migration with HUVECs support. In hypoxic TME, glycolysis may be the primary energy supply pathway. T24 cells then exhibit suppressed proliferation and migration, while HUVECs tend to promote angiogenesis to adapt to the harsh TME.

CD24 Expression and B Cell Maturation Shows a Novel Link With Energy Metabolism: Potential Implications for Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation. In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM). In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p < 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. P < 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2 = 0.76; p < 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro. Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells. In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from peripheral blood. CD24-negative B cells underwent productive proliferation whereas CD24+ B cells were either unresponsive or susceptible to cell death upon BCR-engagement alone. We suggest that CD24 expression may reflect variations in energy metabolism on different B cell subsets.

Mitochondrial Dysfunction and Infection Generate Immunity-Fecundity Tradeoffs in Drosophila.

Physiological responses to short-term environmental stressors, such as infection, can have long-term consequences for fitness, particularly if the responses are inappropriate or nutrient resources are limited. Genetic variation affecting energy acquisition, storage, and usage can limit cellular energy availability and may influence resource-allocation tradeoffs even when environmental nutrients are plentiful. Here, we utilized Drosophila mitochondrial–nuclear genotypes to test whether disrupted mitochondrial function interferes with nutrient-sensing pathways, and whether this disruption has consequences for tradeoffs between immunity and fecundity. We found that an energetically-compromised genotype was relatively resistant to rapamycin—a drug that targets nutrient-sensing pathways and mimics resource limitation. Dietary resource limitation decreased survival of energetically-compromised flies. Furthermore, survival of infection with a natural pathogen was decreased in this genotype, and females of this genotype experienced immunity–fecundity tradeoffs that were not evident in genotypic controls with normal energy metabolism. Together, these results suggest that this genotype may have little excess energetic capacity and fewer cellular nutrients, even when environmental nutrients are not limiting. Genetic variation in energy metabolism may therefore act to limit the resources available for allocation to life-history traits in ways that generate tradeoffs even when environmental resources are not limiting.

Single nucleotide variant profiles of viable single circulating tumour cells reveal CTC behaviours in breast cancer.

Circulating tumour cell (CTC) behaviours are distinct from those of bulk tissues. Thus, treatments to eliminate CTCs differ from the regimens followed to reduce the primary tumour and its metastases. Accordingly, comprehensively deciphering the single nucleotide variant (SNV) profiles in CTCs, which partially determine CTC behaviours, is a priority. Using viable CTCs isolated with the oHSV1-hTERT-GFP virus coupled with fluorescence-activated cell sorting (FACS), the whole genome was amplified using the multiple annealing and looping-based amplification cycle (MALBAC) method. CTC behaviours were evaluated using the SNVs found to be recurrently mutated in different cells (termed CTC-shared SNVs). Analysis of the sequencing data of 11 CTCs from 8 patients demonstrated that SNVs accumulated sporadically among CTCs and their matched primary tumours (22 co-occurring mutated genes were identified in the exomes of CTCs and their matched primary tissues and metastases), and 394 SNVs were shared by at least two CTCs. Mutated APC and LRP1B genes co-occurred in CTC-shared and bulk-tissue SNVs. Additionally, the breast-originating identity of the CTC-shared SNVs was verified, and they demonstrated the following CTC behaviours: i) intravasation competency; ii) increased migration or motility; iii) enhanced cell-cell interactions; iv) variation in energy metabolism; v) an activated platelet or coagulation system; and vi) dysfunctional mitosis. These results demonstrated that it is feasible to capture and amplify the genomes of single CTCs using the described pipeline. CTC-shared SNVs are a potential signature for identifying the origin of the primary tumour in a liquid biopsy. Furthermore, CTCs demonstrated some behaviours that are unique from those of bulk tissues. Therefore, therapies to eradicate these precursors of metastasis may differ from the existing traditional regimens.

Ecotypic differentiation matters for latitudinal variation in energy metabolism and flight performance in a butterfly under climate change.

Life histories of organisms may vary with latitude as they experience different thermal constraints and challenges. This geographic, intraspecific variation could be of significance for range dynamics under climate change beyond edge-core comparisons. In this study, we did a reciprocal transplant experiment between the temperature-regimes of two latitudes with an ectotherm insect, examining the effects on energy metabolism and flight performance. Pararge aegeria expanded its ecological niche from cool woodland (ancestral) to warmer habitat in agricultural landscape (novel ecotype). Northern males had higher standard metabolic rates than southern males, but in females these rates depended on their ecotype. Southern males flew for longer than northern ones. In females, body mass-corrected flight performance depended on latitude and thermal treatment during larval development and in case of the southern females, their interaction. Our experimental study provides evidence for the role of ecological differentiation at the core of the range to modulate ecophysiology and flight performance at different latitudes, which in turn may affect the climatic responsiveness of the species.

Seasonal effects of the UCP3 and the RPTOR gene polymorphisms on obesity traits in Japanese adults.

BackgroundNon-shivering thermogenesis (NST) involves a substantial amount of energy expenditure in humans and, thus, contributes to reducing the risk for obesity. Molecular evolutionary studies have reported that SNPs in/near the uncoupling protein 3 gene (UCP3) and the regulatory associated protein of mTOR complex 1 gene (RPTOR) might influence NST and confer adaptive advantages for modern human dispersal into cold environments. In the present study, the impact of these SNPs on obesity-related traits was investigated.MethodsStudy subjects consisted of 2,834 Japanese adults (percentage of female: 46%, mean age: 51.5). Associations of the UCP3-55C/T and the RPTOR-26934C/T - the 2 potential genetic variations involved in cold adaptation and thermogenic mechanisms in mammals, with quantitative obesity-related traits including body mass index (BMI), waist circumference, visceral fat area (VFA), VFA adjusted for BMI, and selected blood parameters - were tested using multiple linear regression models. Sliding windowsampling analysis was applied to depict seasonal effects of the SNPs on the obesity-related phenotypes.ResultsUCP3-55C/T and the RPTOR-26934C/T did not show any association with obesity traits and blood chemical parameters in multiple linear regression models consisting of the whole subjects. Moreover, sliding window sampling-based association analyses involving seasonality also failed to find associations between these two SNPs and obesity-related traits.ConclusionsUCP3-55C/T and the RPTOR-26934C/T may only have subtle effects on the development of obesity-related traits in the present humans. These two SNPs might be irrelevant to inter-individual variations in energy metabolism and efficiency of NST.

Variations in energy metabolism along the pericardium meridian and its relationship with visceral function adjustments during electroacupuncture

BackgroundElectroacupuncture (EA) is a traditional Chinese medicine treatment guided by meridian theory. As it gradually gains more worldwide acceptance, a clarification of its mechanisms is extremely urgent. We observed variations in transcutaneous oxygen pressure/carbon dioxide pressure (tcpO2/tcpCO2) and microcirculation blood perfusion units (BPU) along the pericardium meridian, and cardiac function during EA at Neiguan (PC6) to explore variations in energy metabolism and its relationship with visceral function adjustments during EA.MethodsTwenty-two healthy volunteers participated in this study. Three channel laser Doppler flowmetry and tcpO2/tcpCO2 detection systems were used to detect tcpO2/tcpCO2 and microcirculation BPU along the pericardium meridian. A hemodynamic monitor was used to detect cardiac function.ResultsIn the normal state, the microcirculatory BPU along the pericardium meridian were significantly higher than that of their bilateral corresponding control points (p < 0.05). During EA at PC6, the values of the microcirculatory BPU along the pericardium meridian did not vary, and few increased. In the normal state, the values of tcpO2 along the pericardium meridian were significantly higher than those of their bilateral corresponding control points (p < 0.05). In addition, the values of tcpCO2 along the pericardium meridian were lower than those of their bilateral corresponding control points. In comparison with the normal state, EA could decrease tcpO2 along the meridian significantly (p < 0.05) and increase tcpCO2. During EA at PC6 in healthy volunteers treated by artificial acute mild hypoxia, cardiac output and cardiac index (p < 0.05) decreased and systemic vascular resistance increased significantly (p < 0.05).ConclusionsIn the normal state, the values of microcirculatory BPU and tcpO2 along the pericardium meridian were both higher than those of their bilateral corresponding control points. Energy metabolism was vigorous along the meridian. During EA, the decrease in oxygen partial pressure along the pericardium meridian might be a result of strengthened energy metabolism of associated tissue and increased oxygen consumption. The variations in energy metabolism along the pericardium meridian during the course of EA had a close relationship with visceral function adjustments.Trial registrationChinese Clinical Trial Registry ChiCTRTRC13003193.

Is there a linkage between metabolism and personality in small mammals? The root vole (Microtus oeconomus) example

Significant inter-individual variation in the rate of animal metabolism is a widespread phenomenon that has started to accumulate general interest. Here we follow recent calls to focus on linkage between the variation in energy metabolism and animal personality. By using wild caught root voles as a study species, we examined the relationship between the behavioral patterns (assessed in open field test) and resting metabolic rate (RMR), both of which are known to show large individual differences and intra-individual consistency in voles. Our results showed only a weak relationship between personality traits and metabolism, since the most parsimonious model (according to AICc) explaining RMR included only body mass and season as factors (explaining 84.8% of variation in RMR). However, the next two alternative models (within ΔAICc=2) also included the personality trait reflecting proactive behaviors (PC1) in addition to body mass, sex and season (85.2 and 85.8% of RMR variance explained, respectively). In all, our study does not provide compelling support for recent ideas of close linkage between behavior and metabolism. Still, our study highlights that even in the case of wild caught individuals, when behavior and metabolism often carry effects of both intrinsic and extrinsic conditions, the potential metabolic effects of varying energetically costly behaviors cannot be neglected.

Seasonal variations in the intermediate metabolism of the crayfish Parastacus brasiliensis (Crustacea, Decapoda, Parastacidae) in the natural environment and experimental culture

The goal of this study was to evaluate the effects of seasonal variations on energy metabolism in different tissues of the freshwater crayfish Parastacus brasiliensis (von Martens, 1869). Crayfish were collected monthly from January 2001 to January 2003 in São Francisco de Paula, Rio Grande do Sul, Brazil, in a stream and in a culture tank. Haemolymph samples were collected from each crayfish in the field with a syringe, by puncturing the membrane at the base of the chelipeds. Hepatopancreas, gills, and abdominal muscle were removed for determination of free glucose, glycogen, total lipids, and triglycerides. The haemolymph samples were used for determination of glucose, total proteins, total lipids, and triglycerides. Statistical analysis revealed significant differences in biochemical composition in crayfish collected in the stream compared to the experimental tank during the year, principally in glucose and triglycerides in haemolymph, glycogen and total lipids in all tissues study, and triglycerides only in abdominal muscle. The regular food intake partially modified these seasonal variations of the metabolic pattern. Environmental conditions (e.g., food availability and water temperature) and reproductive period appeared to be the main factors influencing the seasonal patterns of variation in energy metabolism.

Natural Selection and Adaptive Evolution of Leptin in the Ochotona Family Driven by the Cold Environmental Stress

BackgroundEnvironmental stress can accelerate the evolutionary rate of specific stress-response proteins and create new functions specialized for different environments, enhancing an organism's fitness to stressful environments. Pikas (order Lagomorpha), endemic, non-hibernating mammals in the modern Holarctic Region, live in cold regions at either high altitudes or high latitudes and have a maximum distribution of species diversification confined to the Qinghai-Tibet Plateau. Variations in energy metabolism are remarkable for them living in cold environments. Leptin, an adipocyte-derived hormone, plays important roles in energy homeostasis.Methodology/Principal FindingsTo examine the extent of leptin variations within the Ochotona family, we cloned the entire coding sequence of pika leptin from 6 species in two regions (Qinghai-Tibet Plateau and Inner Mongolia steppe in China) and the leptin sequences of plateau pikas (O. curzonia) from different altitudes on Qinghai-Tibet Plateau. We carried out both DNA and amino acid sequence analyses in molecular evolution and compared modeled spatial structures. Our results show that positive selection (PS) acts on pika leptin, while nine PS sites located within the functionally significant segment 85-119 of leptin and one unique motif appeared only in pika lineages-the ATP synthase α and β subunit signature site. To reveal the environmental factors affecting sequence evolution of pika leptin, relative rate test was performed in pikas from different altitudes. Stepwise multiple regression shows that temperature is significantly and negatively correlated with the rates of non-synonymous substitution (Ka) and amino acid substitution (Aa), whereas altitude does not significantly affect synonymous substitution (Ks), Ka and Aa.Conclusions/SignificanceOur findings support the viewpoint that adaptive evolution may occur in pika leptin, which may play important roles in pikas' ecological adaptation to extreme environmental stress. We speculate that cold, and probably not hypoxia, may be the primary environmental factor for driving adaptive evolution of pika leptin.

Intra-specific variation in resting metabolic rate in MF1 mice is not associated with membrane lipid desaturation in the liver

The ‘membrane pacemaker’ hypothesis provides a putative mechanistic linkage between variations in energy metabolism, rates of ageing and lifespan across different species. Within species we have found positive associations between longevity and metabolism, which contrast the inter-specific trends. It is of interest to know therefore how levels of lipid desaturation in membranes are linked to variation in metabolism between individuals within species. We explored this problem by extracting membrane fatty acids from the livers of mice that varied in their metabolic rate, in a strain (MF1) where we have previously demonstrated a positive association between metabolism and lifespan. We measured resting metabolic rate (RMR) in 60 mice, each measured on three occasions, and measured their body compositions using dual energy X-ray absorptiometry (DXA). We selected 28 individuals that exhibited a wide variation in their mean resting metabolic rates (RMR) and extracted membrane lipids from the livers of these mice post mortem and analysed them for the patterns of contribution of different fatty acids. We then sought associations between the levels of membrane desaturation and the individual variability in RMR, using the proportional contributions of each fatty acid as predictors in a stepwise regression or by re-describing the variation in fatty acyl lipids using a PCA analysis and then seeking associations between scores on the derived components and RMR. We used whole animal RMRs and also RMR with the effects of body composition (fat free mass) removed. The level of individual variation in RMR was consistent with our previous observations. There was a significant positive association ( p = 0.019) between the proportion of palmitic acid (16:0) in the membranes and RMR, which was strengthened ( p = 0.014) when we adjusted RMR for differences in fat free mass. The proportion of palmitic acid (16:0) explained 20.9% of the individual variation in residual RMR. There was no association between RMR or mass adjusted RMR and the proportional representation of any other fatty acid, including 22:6 (DHA) predicted by the membrane pacemaker hypothesis to be of particular significance. High levels of saturated fatty acids in the membranes of mice with high rates of metabolism may contribute to their greater longevity, but the mechanism tying together increased membrane saturation with elevated RMR remains unclear.

Topographical Variation in Metabolic Signatures of Human Gastrointestinal Biopsies Revealed by High-Resolution Magic-Angle Spinning 1H NMR Spectroscopy

Individual and topographical variation in the metabolic profiles of multiple human gastrointestinal tract (GIT) biopsies have been characterized using high-resolution magic-angle spinning (HRMAS) 1H NMR spectroscopy and pattern recognition. Samples from antrum, duodenum, jejunum, ileum, and transverse colon were obtained from 8 male and 8 female participants. Each gut region generated a highly characteristic metabolic profile consistent with the varying structural and functional properties of the tissue at different longitudinal levels of the gut. The antral (stomach) mucosa contained higher levels of choline, glycogen, phosphorylethanolamine, and taurine than other gut regions. The spatially close regions of the duodenum and jejunum were equivalent in terms of their gross biochemical composition with high levels of choline, glutathione, glycerophosphocholine (GPC), and lipids relative to other gut regions. The ileal mucosa showed poor discrimination from the duodenum and jejunum tissues and generated strong amino acids signatures but had relative low GPC signals. The colon (large intestine) was high in acetate, glutamate, inositols, and lactate and low in creatine, GPC, and taurine compared to the small intestine. These longitudinal metabolic variations in the human GIT could be attributed to functional variations in energy metabolism, osmoregulation, gut microbial activity, and oxidative protection. This work indicates that 1H HRMAS NMR studies may be of value in analyzing local metabolic variation due to pathological processes in gut biopsies.

IGF-1 receptor signaling pathways and effects of AMPK activation on IGF-1-induced progesterone secretion in hen granulosa cells

IGF-1 plays a key role in the proliferation and differentiation of granulosa cells. However, the molecular mechanism of IGF-1 action in avian granulosa cells during follicle maturation is unclear. Here, we first studied IGF-1 receptor (IGF-1R) expression, IGF-1-induced progesterone production and some IGF-1R signaling pathways in granulosa cells from different follicles. IGF-1R (mRNA and protein) was higher in fresh or cultured granulosa cells from the largest follicles (F1 or F2) than in those from smaller follicles (F3 or F4). In vitro, IGF-1 treatment (10 −8 M, 36 h) increased progesterone secretion by four-fold in mixed F3 and F4 (F3/4) granulosa cells and by 1.5-fold in F1 granulosa cells. IGF-1 (10 −8 M, 30 min)-induced increases in tyrosine phosphorylation of IGF-1R beta subunit and phosphorylation of ERK were higher in F1 than in F3/4 granulosa cells. Interestingly, IGF-1 stimulation (10 −8 M, 10 min) decreased the level of AMPK Thr172 phosphorylation in F1 and F3/4 granulosa cells. We have recently showed that AMPK (AMP-activated protein kinase) is a protein kinase involved in the steroidogenesis in chicken granulosa cells. We then studied the effects of AMPK activation by AICAR (5-aminoimidazole-4-carboxamide ribonucleoside), an activator of AMPK, on IGF-1-induced progesterone secretion by F3/4 and F1 granulosa cells. AICAR treatment (1 mM, 36 h) increased IGF-1-induced progesterone secretion, StAR protein levels and decreased ERK phosphorylation in F1 granulosa cells. Opposite data were observed in F3/4 granulosa cells. Adenovirus-mediated expression of dominant negative AMPK totally reversed the effects of AICAR on IGF-1-induced progesterone secretion, StAR protein production and ERK phosphorylation in both F3/4 and F1 granulosa cells. Thus, a variation of energy metabolism through AMPK activation could modulate differently IGF-1-induced progesterone production in F1 and F3/4 granulosa cells.

Effects of xylanase supplementation on between-bird variation in energy metabolism and the number of Clostridium perfringens in broilers fed a wheat-based diet

Three experiments were conducted to examine: (a) the apparent metabolisable energy (AME) contents, the level of non-starch polysaccharides (NSP), and the extract viscosity value of 9 wheat samples; (b) the efficacy of a xylanase in reducing between-bird variation for AME; and (c) the effect of a xylanase on the number of Clostridium perfringens in broilers fed a low AME wheat diet. Experiment 1 revealed that the AME value of wheat varied from 11.5 to 13.6 MJ/kg dry matter (DM), which negatively correlated with the total NSP level (r = –0.97). Experiment 2 involved a 48-cage individual bird trial, where xylanase increased (P &lt; 0.05) the AME from 12.51 to 13.09 MJ/kg DM and reduced (P &lt; 0.05) its standard deviation from 1.13 to 0.52. The standard deviation for feed conversion ratio, ileal viscosity, and faecal viscosity was also reduced. In this experiment, there was a strong correlation between AME and excreta viscosity (r = –0.81) and the caecal xylanase activity of birds fed the control diet was positively correlated with AME (r = 0.72). In Expt 3, xylanase reduced the number of Clostridium perfringens, the causative agent for necrotic enteritis, to a non-detectable level in the ileum and caeca of broilers fed a low-ME wheat diet.