Source Of Metabolic Energy Research Articles

Sodium-glucose cotransporters: new targets of cancer therapy?

Glucose, the key source of metabolic energy, is imported into cells by two categories of transporters: 1) facilitative glucose transporters (GLUTs) and 2) secondary active sodium-glucose cotransporters (SGLTs). Cancer cells have an increased demand for glucose uptake and utilisation compared to normal cells. Previous studies have demonstrated the overexpression of GLUTs, mainly GLUT1, in many cancer types. As the current standard positron emission tomography (PET) tracer 2-deoxy-2-(18F)fluoro-D-glucose (2-FDG) for imaging tumour cells via GLUT1 lacks in sensitivity and specificity, it may soon be replaced by the newly designed, highly sensitive and specific SGLT tracer α-methyl-4-(F-18)fluoro-4-deoxy-Dglucopyranoside (Me-4FDG) in clinical detection and tumour staging. This tracer has recently demonstrated the functional activity of SGLT in pancreatic, prostate, and brain cancers. The mRNA and protein expression of SGLTs have also been reported in colon/colorectal, lung, ovarian, head, neck, and oral squamous carcinomas. So far, SGLTs have been poorly investigated in cancer, and their protein expression and localisation are often controversial due to a lack of specific SGLT antibodies. In this review, we describe current knowledge concerning SGLT1 and SGLT2 (over)expression in various cancer types. The findings of SGLTs in malignant cells may help in developing novel cancer therapies with SGLT2 or SGLT1/SGLT2 inhibitors already used in diabetes mellitus treatment.

GLUCOSE LEVEL ANALYSIS ON STORED PACKED RED CELLS

The main source of energy for red cell metabolism is glucose via glycolytic pathway. Red cells metabolism slows down during storage at 2–6OC. Biochemical changes during storage are called storage lesions, i.e. decreased pH, glucose, and ATP, lactic acid accumulation, and loss of red cells function. Samples taken from the tip of PRC bags in CPDA-1 of the same code are divided into four sections, and stored in the blood bank refrigerator at 2–6OC. Glucose level is measured using ABX Pentra 400 (Horiba, Japan) on storage day 3 as a control, day 7, day 14, and day 21. Glucose levels during storage decreased significantly between day 3, and day 7 (p < 0.001), between day 7, and day 14 (p < 0.001), and between day 14, and 21 (p < 0.001). Glucose levels of Packed Red Cells (PRC) decrease during storage. Glycolysis occurs during storage although metabolism slows down.

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii.

Peroxisomes are central to eukaryotic metabolism, including the oxidation of fatty acids—which subsequently provide an important source of metabolic energy—and in the biosynthesis of cholesterol and plasmalogens. However, the presence and nature of peroxisomes in the parasitic apicomplexan protozoa remains controversial. A survey of the available genomes revealed that genes encoding peroxisome biogenesis factors, so-called peroxins (Pex), are only present in a subset of these parasites, the coccidia. The basic principle of peroxisomal protein import is evolutionarily conserved, proteins harbouring a peroxisomal-targeting signal 1 (PTS1) interact in the cytosol with the shuttling receptor Pex5 and are then imported into the peroxisome via the membrane-bound protein complex formed by Pex13 and Pex14. Surprisingly, whilst Pex5 is clearly identifiable, Pex13 and, perhaps, Pex14 are apparently absent from the coccidian genomes. To investigate the functionality of the PTS1 import mechanism in these parasites, expression of Pex5 from the model coccidian Toxoplasma gondii was shown to rescue the import defect of Pex5-deleted Saccharomyces cerevisiae. In support of these data, green fluorescent protein (GFP) bearing the enhanced (e)PTS1 known to efficiently localise to peroxisomes in yeast, localised to peroxisome-like bodies when expressed in Toxoplasma. Furthermore, the PTS1-binding domain of Pex5 and a PTS1 ligand from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2) were shown to interact in vitro. Taken together, these data demonstrate that the Pex5–PTS1 interaction is functional in the coccidia and indicate that a nonconventional peroxisomal import mechanism may operate in the absence of Pex13 and Pex14.

Cellulose degradation in Gastrophysa viridula (Coleoptera: Chrysomelidae): functional characterization of two CAZymes belonging to glycoside hydrolase family 45 reveals a novel enzymatic activity.

Cellulose is a major component of the primary and secondary cell walls in plants. Cellulose is considered to be the most abundant biopolymer on Earth and represents a large potential source of metabolic energy. Yet, cellulose degradation is rare and mostly restricted to cellulolytic microorganisms. Recently, various metazoans, including leaf beetles, have been found to encode their own cellulases, giving them the ability to degrade cellulose independently of cellulolytic symbionts. Here, we analyzed the cellulosic capacity of the leaf beetle Gastrophysa viridula, which typically feeds on Rumex plants. We identified three putative cellulases member of two glycoside hydrolase (GH) families, namely GH45 and GH9. Using heterologous expression and functional assays, we demonstrated that both GH45 proteins are active enzymes, in contrast to the GH9 protein. One GH45 protein acted on amorphous cellulose as an endo-β-1,4-glucanase, whereas the other evolved to become an endo-β-1,4-xyloglucanase. We successfully knocked down the expression of both GH45 genes using RNAi, but no changes in weight gain or mortality were observed compared to control insects. Our data indicated that the breakdown of these polysaccharides in G. viridula may facilitate access to plant cell content, which is rich in nitrogen and simple sugars.

Effects of different dietary lipids concentrations on the egg production and egg quality produced by Macrobrachium acanthurus females

The sexual maturation and reproduction of crustaceans are very demanding processes for energy and nutrients. Females require the nutrients to deposit them into the eggs and allow the healthy development of embryos and early larvae survival. The lipids are essential nutrients related to the sexual maturation and the egg production, as they are sources of metabolic energy for the gonad development, as well structural molecules for the embryonic tissue formation. This work presents the effects of different dietary lipid levels (10, 12.5, 15, 17.5 and 20% of a mixture of krill and cod liver oil as lipid sources), on the growth, egg production, and egg quality, of freshwater prawn Macrobrachium acanthurus females fed during 60 days. The results showed that an inclusion higher than 15% of lipids, improved the egg production and the content of protein and lipids significantly. A lipid inclusion between 15 and 17.5% might be optimal for maturation and egg production of the females of M. acanthurus .

Aplikasi Berbagai Dosis dan Dua Jenis Guano pada Budidaya Tanaman Jagung Pakan (Zea mays. L) di Lahan Podsolik

Corn feed is one animal feed that has many advantages, as corn feed is used for metabolic energy sources. Podsolic land is a land with very low nutrient value. This study aims to (i) determine the effect of various doses, and two types of guano interactions, (ii) determine the effect of various doses of guano, (iii) find out influence of two types of guano, (iv) get the best interaction, (v) get the best dose, (vi) get the best type of guano in the cultivation of corn feed in podsolic land. This research was conducted in Hawang Village, Limpasu District, Hulu Sungai Tengah Regency, from March to June 2018. They are using Group Random Design (GRD) Factorial 2 factors. The first factor is various doses of guano with five levels: d1 = 1.5 kg. plot-1, d2 = 3 kg. plot-1, d3 = 4.5 kg. plot-1, d4 = 6 kg. plot-1, d5 = 7.5 kg. plot-1. The second factor is two types of guano with two levels: g1 = bat guano, g2 = swallow guano. The results showed that the interaction between various doses and two types of guano had no effect on growth and yield, except that the effect was very significant on long cob weighted, whereas a single factor of various doses had significant and very real effect on all observation variables and the factor of two types of guano had no effect on all variables. Except for significant effect on plant height growth at the age of 56 HST.

Increased Amino Acid Uptake Supports Autophagy-Deficient Cell Survival upon Glutamine Deprivation

Autophagy is a protein degradation process by which intracellular materials are recycled for energy homeostasis. However, the metabolic status and energy source of autophagy-defective tumor cells are poorly understood. Here, our data show that amino acid uptake from the extracellular environment is increased in autophagy-deficient cells upon glutamine deprivation. This elevated amino acid uptake results from activating transcription factor 4 (ATF4)-dependent upregulation of AAT (amino acid transporter) gene expression. Furthermore, we identify SIRT6, a NAD+-dependent histone deacetylase, as a corepressor of ATF4 transcriptional activity. In autophagy-deficient cells, activated NRF2 enhances ATF4 transcriptional activity by disrupting the interaction between SIRT6 and ATF4. In this way, autophagy-deficient cells exhibit increased AAT expression and show increased amino acid uptake. Notably, inhibition of amino acid uptake reduces the viability of glutamine-deprived autophagy-deficient cells, but not significantly in wild-type cells, suggesting reliance of autophagy-deficient tumor cells on extracellular amino acid uptake.

Effects of the recombinant crustacean hyperglycemic hormones rCHH-B1 and rCHH-B2 on the osmo-ionic regulation of the shrimp Litopenaeus vannamei exposed to acute salinity stress.

The Pacific white shrimp Litopenaeus vannamei is a euryhaline organism that copes with salinity fluctuations in the environment; therefore, its osmotic and ionic regulation abilities are vital. Osmoregulation may be controlled by the crustacean hyperglycemic hormone (CHH), a neuropeptide mainly expressed in the eyestalks. In L. vannamei, CHH-B1 and CHH-B2 are CHH isoforms isolated from the eyestalks whose expression is influenced by environmental salinity. It has been suggested that they are involved in the response to salinity stress. To clarify this, we investigated the effect of the recombinant peptides, rCHH-B1 and rCHH-B2, on the osmo-ionic regulation of shrimp acutely exposed to different salinity conditions (8, 26 and 45‰). Both rCHHs promoted differential effects on the osmoregulatory capacity (OC) and the ionoregulatory capacity (IC) for hemolymph Na+ and Cl- during iso-osmotic (26‰) and hyper-osmotic (45‰) transfers. These changes were linked to the changes observed in Na+/K+ ATPase and carbonic anhydrase gene expression in gills, especially under high salinity conditions, suggesting that the hormones may regulate the expression of these genes. Glucose and protein levels measured during acute salinity transfer suggest their roles as sources of metabolic energy for osmotic regulation or as organic osmolytes. These results taken together suggest that both the CHH-B1 and CHH-B2 peptides are important regulators of the physiological response of L. vannamei to acute salinity fluctuations.

Differences in the distribution and optical properties of DOM between fresh and saline lakes in a semi-arid area of Northern China

In limnological environments, most organic carbon is present in the dissolved form. Dissolved organic carbon (DOC) is the main source of energy for microbial metabolism and biosynthesis, and also affects photosynthetic radiation level and the attenuation of ultraviolet irradiation to protect aquatic organisms. There are large differences in DOC concentration, source, and characteristics due to regional variations in water quality and basin characteristics. Reliable estimates of DOC and analysis of optical characteristics are crucial to understand the true role of lakes in the global carbon cycle. In this article, the distribution of DOC across 30 lakes in semi-arid areas of Northern China is reported. The data shows that saline lakes exhibited higher DOC concentrations than freshwater lakes, and the positive relationship between salinity and DOC was established (R2 = 0.42, p < 0.01, n = 196). The mean DOC concentration in eutrophic lakes was lower than in mesotrophic and oligotrophic lakes. Analysis of optical characteristics of CDOM indicated that saline lakes in this semi-arid regions contained abundant fulvic acid, and greater levels of autochthonous dissolved organic matter (DOM) with a lower molecular mass than fresh waters. The total suspended matter (TSM) is the main factor influencing on SUVA254 in both freshwater and saline lakes with a negative correlation. SUVA254 was negatively correlated with the salinity only in freshwater lakes, and with pH only in saline lakes. The result suggests that it was doubtful whether CDOM or SUVA254 alone can be a predictor of DOC concentration and other water quality parameters, especially in different types of lakes with different optical and physicochemical characteristics.

Good, Bad, or Ugly: the Biological Roles of Bone Marrow Fat.

Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.

A genome-wide screen in Escherichia coli reveals that ubiquinone is a key antioxidant for metabolism of long-chain fatty acids

Long-chain fatty acids (LCFAs) are used as a rich source of metabolic energy by several bacteria including important pathogens. Because LCFAs also induce oxidative stress, which may be detrimental to bacterial growth, it is imperative to understand the strategies employed by bacteria to counteract such stresses. Here, we performed a genetic screen in Escherichia coli on the LCFA, oleate, and compared our results with published genome-wide screens of multiple non-fermentable carbon sources. This large-scale analysis revealed that among components of the aerobic electron transport chain (ETC), only genes involved in the biosynthesis of ubiquinone, an electron carrier in the ETC, are highly required for growth in LCFAs when compared with other carbon sources. Using genetic and biochemical approaches, we show that this increased requirement of ubiquinone is to mitigate elevated levels of reactive oxygen species generated by LCFA degradation. Intriguingly, we find that unlike other ETC components whose requirement for growth is inversely correlated with the energy yield of non-fermentable carbon sources, the requirement of ubiquinone correlates with oxidative stress. Our results therefore suggest that a mechanism in addition to the known electron carrier function of ubiquinone is required to explain its antioxidant role in LCFA metabolism. Importantly, among the various oxidative stress combat players in E. coli, ubiquinone acts as the cell's first line of defense against LCFA-induced oxidative stress. Taken together, our results emphasize that ubiquinone is a key antioxidant during LCFA metabolism and therefore provides a rationale for investigating its role in LCFA-utilizing pathogenic bacteria.

Two-Dimensional Array ATP/ADP Sensitive Image Sensor with a Uniform Distribution of Chemically Immobilized Apyrase

Abstract ATP and ADP are the major energy source in metabolism of cells, and furthermore ATP works as an important extracellular signaling material. ATP bioimaging is required to understand their metabolism. In this paper, a label-free ATP/ADP image sensor was fabricated using a 128 × 128 (16 k) pixel array semiconductor CCD-type pH image sensor and Apyrase. The principle is based on measuring protons produced by the enzyme reaction between Apyrase and ATP or ADP. In order to put a uniform potential response of the sensor into practice, two different methods, (3-APTES and CEST), which chemically fixed N-terminal of Apyrase with the sensor were examined. The sensor modified by the CEST method had a quite clean surface microscopically and demonstrated a fine real-time image monitoring the ATP concentration. The potential response of the image sensor was characterized; effect of buffer solution, calibration curves of ATP and ADP, durability, the limit of detection (LOD) for ATP, and the response of time. The potential distribution for effective pixels to ATP concentration was narrow, single and symmetrical. Due to 16 K sensing pixels finely responding to ATP concentration uniformly, the LOD of ATP concentration (10 µM) was exactly determined with a statistical treatment.

Restoration of Impaired Metabolic Energy Balance (ATP Pool) and Tube Formation Potential of Endothelial Cells under "high glucose", Diabetic Conditions by the Bioinorganic Polymer Polyphosphate.

Micro-vascularization is a fast, energy-dependent process that is compromised by elevated glucose concentrations such as in diabetes mellitus disease. Here, we studied the effect of the physiological bioinorganic polymer, polyphosphate (polyP), on the reduced ATP content and impaired function of endothelial cells cultivated under “high glucose” (35 mM diabetes mellitus conditions) concentrations. This high-energy biopolymer has been shown to provide a source of metabolic energy, stored in its phosphoanhydride bonds. We show that exposure of human umbilical vein endothelial cells (HUVEC cells) to “high glucose” levels results in reduced cell viability, increased apoptotic cell death, and a decline in intracellular ATP level. As a consequence, the ability of HUVEC cells to form tube-like structures in the in vitro cell tube formation assay was almost completely abolished under “high glucose” conditions. Those cells were grown onto a physiological collagen scaffold (collagen/basement membrane extract). We demonstrate that these adverse effects of increased glucose levels can be reversed by administration of polyP to almost normal values. Using Na-polyP, complexed in a stoichiometric (molar) ratio to Ca2+ ions and in the physiological concentration range between 30 and 300 µM, an almost complete restoration of the reduced ATP pool of cells exposed to “high glucose” was found, as well as a normalization of the number of apoptotic cells and energy-dependent tube formation. It is concluded that the adverse effects on endothelial cells caused by the metabolic energy imbalance at elevated glucose concentrations can be counterbalanced by polyP, potentially opening new strategies for treatment of the micro-vascular complications in diabetic patients.

Collagen-inducing biologization of prosthetic material for hernia repair: Polypropylene meshes coated with polyP/collagen.

Prostethic mesh material such as nonabsorbable polypropylene used in open and laparoscopic hernia repair are characterized by controllable mechanical properties but may elicit undesirable physiological reactions due to the nonphysiological inert polymer material. We succeeded in developing a biocompatible coating for these meshes, based on a physiological inorganic polymer, polyphosphate (polyP) that is morphogenetically active and used as a metabolic energy source, and a collagen matrix. The polyP/collagen hydrogel material was prepared by a freeze-extraction method, with amorphous Ca-polyP microparticles. Electron microscopy (SEM and REM) studies revealed that the polyP/collagen coats are built up of ≈50 nm-sized microparticles deposited onto the collagen matrix which forms a continuous layer around the polypropylene fibers that also spans the mesh pores. This bioresorbable inorganic/organic hybrid coat was found to be degraded during three days of incubation in medium/serum. The biomechanical properties of the coated meshes are comparable to those of the unmodified polypropylene meshes, with a higher toughness in longitudinal orientation and a more pronounced extensibility in the transverse orientation. The polyP/collagen coating improved cell attachment to the polypropylene meshes and strongly increase the growth of fibroblasts (MC3T3-E1 cells). Furthermore, those mats upregulate the expression of the gene encoding the stromal cell-derived factor-1α (SDF-1), a mesenchymal stem cells attracting chemokine in the fibroblasts. We conclude that coating of inert polymer meshes with a biocompatible, collagen-inducing polyP/collagen inorganic/organic hybrid layer may improve tissue integration of the meshes and the outcome of surgical hernia repair and may redudce the foreign body reaction in contaminated field. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2109-2121, 2018.

Microbial oxidation as a methane sink beneath the West Antarctic Ice Sheet

Aquatic habitats beneath ice masses contain active microbial ecosystems capable of cycling important greenhouse gases, such as methane (CH4). A large methane reservoir is thought to exist beneath the West Antarctic Ice Sheet, but its quantity, source and ultimate fate are poorly understood. For instance, O2 supplied by basal melting should result in conditions favourable for aerobic methane oxidation. Here we use measurements of methane concentrations and stable isotope compositions along with genomic analyses to assess the sources and cycling of methane in Subglacial Lake Whillans (SLW) in West Antarctica. We show that sub-ice-sheet methane is produced through the biological reduction of CO2 using H2. This methane pool is subsequently consumed by aerobic, bacterial methane oxidation at the SLW sediment–water interface. Bacterial oxidation consumes >99% of the methane and represents a significant methane sink, and source of biomass carbon and metabolic energy to the surficial SLW sediments. We conclude that aerobic methanotrophy may mitigate the release of methane to the atmosphere upon subglacial water drainage to ice sheet margins and during periods of deglaciation. Subglacial lakes contain active microbial ecosystems capable of cycling methane. In a subglacial lake in West Antarctica, methane that is produced is subsequently consumed, limiting the potential for methane emissions during lake drainage.

Geochemical bioenergetics during low‐temperature serpentinization: An example from the Samail ophiolite, Sultanate of Oman

Abstract Various classes of microbial and biomolecular evidence from global studies in marine and continental settings are used to identify a set of reactions that appear to support microbial metabolism during serpentinization of ultramafic rocks. Geochemical data from serpentinizing ecosystems in the Samail ophiolite of Oman are used to evaluate the extent of disequilibria that can support this set of microbial metabolisms, and to provide a ranking of potential metabolic energy sources in hyperalkaline fluids that are direct products of serpentinization. Results are used to construct hypotheses for how microbial metabolism may be supported in the subsurface for two cases: ecosystems hosted in rocks that have already undergone significant serpentinization, and those hosted by deeper, active serpentinization processes.

Dopamine D2 Receptor Signaling in the Nucleus Accumbens Comprises a Metabolic-Cognitive Brain Interface Regulating Metabolic Components of Glucose Reinforcement.

Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA) and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2Rs) also regulate reinforcement learning and are implicated in glucose-related metabolic disorders. Nevertheless, interactions between striatal D2R and peripheral glucose have not been previously described. Here we show that manipulations involving striatal D2R signaling coincide with perseverative and impulsive-like responding for sucrose, a disaccharide consisting of fructose and glucose. Fructose conveys orosensory (ie, taste) reinforcement but does not convey metabolic (ie, nutrient-derived) reinforcement. Glucose however conveys orosensory reinforcement but unlike fructose, it is a major metabolic energy source, underlies sustained reinforcement, and activates striatal circuitry. We found that mice with deletion of dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) exclusively in D2R-expressing cells exhibited preferential D2R changes in the nucleus accumbens (NAc), a striatal region that critically regulates sucrose reinforcement. These changes coincided with perseverative and impulsive-like responding for sucrose pellets and sustained reinforcement learning of glucose-paired flavors. These mice were also characterized by significant glucose intolerance (ie, impaired glucose utilization). Systemic glucose administration significantly attenuated sucrose operant responding and D2R activation or blockade in the NAc bidirectionally modulated blood glucose levels and glucose tolerance. Collectively, these results implicate NAc D2R in regulating both peripheral glucose levels and glucose-dependent reinforcement learning behaviors and highlight the notion that glucose metabolic impairments arising from disrupted NAc D2R signaling are involved in compulsive and perseverative feeding behaviors.

Negative correlation between CSF lactate levels and MoCA scores in male Chinese subjects

Lactate is a product of glycolysis by astrocytes and can be generated as a primary metabolic energy source by neurons. Lactate plays multifunctional role in human brain energy metabolism and cognitive function. However, no direct evidence demonstrated the link between lactate and cognition in normal condition. In the present study, concentrations of lactate in cerebrospinal fluid (CSF) and peripheral blood were measured to investigate the association of lactate with cognitive ability, which was assessed by Montreal Cognitive Assessment (MoCA), in 99 male Chinese subjects. Correlation analyses revealed that serum lactate levels were negatively correlated with age, and CSF lactate levels were negatively correlated with MoCA scores after Box-Cox transformations. But no correlation was found between serum lactate levels and MoCA scores after Box-Cox transformations. In conclusion, the results indicate that CSF lactate levels were negatively correlated with MoCA scores in male Chinese subjects.

Glucose Transporters in Brain: In Health and in Alzheimer's Disease.

Neurons need a continuous supply of glucose, the major source of energy for mammalian brain metabolism. The central nervous system is protected by three main physiological cell barriers. Cell membranes are impermeable for glucose, therefore glucose is transferred across the cell membranes by specific transport proteins: sodium-independent glucose transporters (GLUTs), encoded by SLC2 genes, and sodium-dependent glucose transporters (for example SGLTs), encoded by SLC5 genes. Human brain expresses 10 GLUT proteins and 10 proteins encoded by SLC5 genes. In patients with brain diseases, particularly Alzheimer's (AD) and Huntington's diseases, abnormalities in neuronal glucose metabolism have been showed. The levels of GLUT1 and GLUT3, the major brain glucose transporters, are decreased, especially in the cerebral cortex. Therefore, in AD, hypometabolism of glucose and deficits in energy are observed. Production of ATP from glucose metabolism in sporadic AD declines to 50% and the tendency to decline continues throughout the progression of the disease. This decrease is correlated with O-GlcAcetylation and tau hyperphosphorylation, as the compensatory mechanisms in AD are the utilization of endogenous brain substances and drastic increase in GLUT2 levels. The present review focuses on the changes in the expression of glucose transporters due to AD.

85 REGULATION OF STEAROYL-CoENZYME A DESATURASE BY FATTY ACIDS IS ESSENTIAL TO PORCINE EARLY EMBRYO DEVELOPMENT

Various fatty acids are found in large amounts in follicular fluid and the uterus. These fatty acids are known to regulate lipid metabolism in a mammal’s embryo. Lipid metabolism provides a source of energy, and its importance during embryogenesis is being increasingly recognised. Especially, the pig has larger amounts of intercellular lipid bilayers in the embryo than do other species, which indicates the porcine embryo is more dependent on fatty acid on their metabolic pathway. This study investigated the transcriptome analysis data of in vivo embryos and the effect of oleic acid (C18:1n-9) and stearic acid (C18:0) on in vitro-produced porcine embryos. In transcriptome analysis of in vivo embryos, we found several genes were increasing before and after maternal zygotic transition stage, and interactions were mapped and given a significance score. Among these genes, stearoyl-coenzyme A desaturase (SCD) gene was significantly increased during 8-cell to blastocyst stage. Stearoyl-coenzyme A desaturase is responsible for converting saturated fatty acid (stearic acid) to monounsaturated fatty acid (oleic acid). Furthermore, we treated with oleic acid (50, 100, 250, and 500 μM) and stearic acid (50, 75, and 100 μM) on 2 day and 4 day after parthenogenetic embryos. Both oleic acid and stearic acid concentration over 100 μM had a negative effect on blastocyst formation rate and cell numbers because of exogenous fatty acid toxicity. In addition, there was no significant difference among all stearic acid treated groups and total cell number of oleic acid treated blastocyst. However, the 2-day oleic acid treated group (45.92 ± 4.01, n = 8, 2 day, 100 μM) had a significant increase of blastocyst formation rate (P &lt; 0.05) compared with the control group (34.88 ± 2.93, n = 8). These data could support that porcine embryos can use exogenous oleic acid as a metabolic energy source. The data also demonstrate the important role of SCD in porcine early embryo development. To confirm the transcriptome analysis, we are investigating mRNA level of SCD on in vitro-produced embryos at 1-cell to morula and blastocyst stage on the control group, oleic acid treated group, fetal bovine serum treated group, and nontreated group. Furthermore, we are investigating SCD inhibition assay by A939572 (SCD inhibitor) on parthenogenetic embryos in a fetal bovine serum treated group and nontreated group for identifying blastocyst formation rate and total cell numbers. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2055199) and Next BioGreen 21 program (PJ0113002016), Rural Development Administration, Republic of Korea.