Source Of Metabolic Energy Research Articles

Optimization of diesel oil biodegradation in seawater using statistical experimental methodology

Petroleum hydrocarbons released into the environment can be harmful to higher organisms, but they can be utilized by microorganisms as the sole source of energy for metabolism. To investigate the optimal conditions of diesel oil biodegradation, the Plackett-Burman (PB) design was used for the optimization in the first step, and N source (NaNO₃), P source (KH₂PO₄) and pH were found to be significant factors affecting oil degradation. Then the response surface methodology (RSM) using a central composite design (CCD) was adopted for the augmentation of diesel oil biodegradation and a fitted quadratic model was obtained. The model F-value of 27.25 and the low probability value (<0.0001) indicate that the model is significant and that the concentration of NaNO₃N, KH₂PO₄ and pH had significant effects on oil removal during the study. Three-dimensional response surface plots were constructed by plotting the response (oil degradation efficiency) on the z-axis against any two independent variables, and the optimal biodegradation conditions of diesel oil (original total petroleum hydrocarbons 125 mg/L) were determined as follows: NaNO₃ 0.143 g, KH₂PO₄ 0.022 g and pH 7.4. These results fit quite well with the C, N and P ratio in biological cells. Results from the present study might provide a new method to estimate the optimal nitrogen and phosphorus concentration in advance for oil biodegradation according to the composition of petroleum.

B18 Glucose metabolism is reduced in Huntington disease: in-vivo and in-vitro evidence

Background Huntington disease (HD) a progressive brain dysfunction and degeneration caused by characterised by CAG repeat expansion mutation, that is translated into results polyglutamine tract in huntingtin (Htt), a protein whose size-dependent toxicity influences age at onset. Mutant Htt (mHtt) interferes with several essential biologic processes, including defective energy metabolism. Glucose is the primary source of metabolic energy for the brain and defects in glucose utilisation can virtually affect brain activities. Aim Our first aim was to test whether basal glucose metabolism in subjects with a genetic risk of HD may influence onset of manifest symptoms. Second we proposed to investigate how glucose levels might modulate neuronal vulnerability to dysfunction in presence of mHtt. Methods Functional study in HD patients. 43 presymptomatic HD subjects underwent 18F-FDG PET scan and prospectively followed up for at least 5 years. Clinical changes were detected by using the unified HD rating scale. In vitro study Mouse striatal-derived cells expressing mHtt (STHdh111/111) were cultured in absence or in presence of different concentrations of glucose. Cell survival was then determined by Annexin V staining. Results Of the 43 preHD subjects who manifested motor symptoms, after 5 years from 18F-FDG PET scan, 26 showed a loss of glucose utilisation in the caudate, that was significantly lower than the 17 preHD subjects who remained symptoms-free (p Conclusion Reduced glucose metabolism exerts an important impact on neuronal function and in the brain caudate may represent a predisposing factor that contributes to the age at onset of HD in preHD subjects.

SCS3 and YFT2 Link Transcription of Phospholipid Biosynthetic Genes to ER Stress and the UPR

The ability to store nutrients in lipid droplets (LDs) is an ancient function that provides the primary source of metabolic energy during periods of nutrient insufficiency and between meals. The Fat storage-Inducing Transmembrane (FIT) proteins are conserved ER–resident proteins that facilitate fat storage by partitioning energy-rich triglycerides into LDs. FIT2, the ancient ortholog of the FIT gene family first identified in mammals has two homologs in Saccharomyces cerevisiae (SCS3 and YFT2) and other fungi of the Saccharomycotina lineage. Despite the coevolution of these genes for more than 170 million years and their divergence from higher eukaryotes, SCS3, YFT2, and the human FIT2 gene retain some common functions: expression of the yeast genes in a human embryonic kidney cell line promotes LD formation, and expression of human FIT2 in yeast rescues the inositol auxotrophy and chemical and genetic phenotypes of strains lacking SCS3. To better understand the function of SCS3 and YFT2, we investigated the chemical sensitivities of strains deleted for either or both genes and identified synthetic genetic interactions against the viable yeast gene-deletion collection. We show that SCS3 and YFT2 have shared and unique functions that connect major biosynthetic processes critical for cell growth. These include lipid metabolism, vesicular trafficking, transcription of phospholipid biosynthetic genes, and protein synthesis. The genetic data indicate that optimal strain fitness requires a balance between phospholipid synthesis and protein synthesis and that deletion of SCS3 and YFT2 impacts a regulatory mechanism that coordinates these processes. Part of this mechanism involves a role for SCS3 in communicating changes in the ER (e.g. due to low inositol) to Opi1-regulated transcription of phospholipid biosynthetic genes. We conclude that SCS3 and YFT2 are required for normal ER membrane biosynthesis in response to perturbations in lipid metabolism and ER stress.

A generic model of growth, energy metabolism, and body composition for cattle and sheep1

A generic daily time-step model of animal growth and metabolism for cattle and sheep is described. It includes total BW as well as protein, water, and fat components, and also energy components associated with the growth of protein and fat, and activity costs. Protein decay is also incorporated, along with the energy costs of resynthesising degraded protein. Protein weight is taken to be the primary indicator of metabolic state, and fat is regarded as a potential source of metabolic energy for physiological processes such as the resynthesis of degraded protein. Normal weight is defined as maximum protein and the associated fat component so that if the BW of the animal exceeds the normal value, all excess weight is in the form of fat. It is assumed that the normal fat fraction increases from birth to maturity. There are relatively few parameters, all of which have a reasonable physiological interpretation, which helps simplify choosing parameters for different animal types and breeds. Simulations for growing and mature cattle and sheep in response to varying available ME are presented and comparisons with empirical curves reported in the literature for body composition are in excellent agreement.

Developmental and moult cycle related biochemical changes in larvae of the spider crab, &lt;i&gt;Maja brachydactyla&lt;/i&gt; (Brachyura: Majidae)

Ontogenetic changes in dry weight, elemental composition (CHN), and digestive enzyme activities (total protease, amylase) were studied during the moulting cycle of all larval instars (zoea I-II, megalopa; ZI, ZII, M) of the spider crab Maja brachydactyla Balss, 1922 reared in the laboratory. A gradual but significant increase in biomass was observed throughout the zoeal instars, followed by steeper growth in the megalopa. Maximum values were reached in moult stage D 2 . Digestive enzyme activities also increased significantly throughout larval development. The ZI showed a continuous increase in total protease activity during its moult cycle, suggesting that newly hatched larvae have a gradually increasing need to take up proteins to provide amino acids, which are prime materials for growth and development, and possibly to use them as a metabolic energy source. The largest variations in digestive enzyme activites in relation to the moult cycle were observed in the megalopa instar. After an initial increase in postmoult, enzyme activities decreased to low levels similar to those measured in the zoeal instars at intermoult, followed by another increase to a maximum level in premoult. Metamorphosis involves great physiological and behavioural changes, which could explain the large variations in the megalopa moult cycle. We therefore suggest that the moult cycle stages should be taken into account when nutritional condition indices are used to estimate the physiological performance of decapod crustacean larvae.

Apoptosis, necrosis and autophagy are influenced by metabolic energy sources in cultured rat spermatocytes

Apoptosis, necrosis and autophagy are mechanistically related processes that control tissue homeostasis and cell survival. In the testis, germ cell death is important for controlling sperm output, but it is unknown whether or not germ cells can switch from apoptosis to necrosis, as has been reported in other tissues. Furthermore, autophagy has not been reported in spermatogenesis. Spermatocytes (meiotic cells) and spermatids (haploid cells) use lactate rather than glucose as their primary substrate for producing ATP. The metabolism of glucose, but not lactate, reduces ATP levels and increases intracellular [H(+)] and [Ca(2+)], both of which are associated with apoptosis and/or necrosis in somatic cells. In this work, we evaluated whether different energy sources, such as lactate or glucose, can influence spermatocyte death type and/or survival in primary cultures. Spermatocytes cultured for 12 h without an energy source died by necrosis, while spermatocytes cultured with 5 mM glucose showed a significant increase in apoptosis, as evidenced by caspase activity, TUNEL assay and phosphatidylserine exposure. Apoptosis was not observed in spermatocytes cultured with 5 mM lactate or deoxyglucose. Autophagy markers, such as LC3-II and autophagosomes, were detected after 12 h of culture, regardless the culture conditions. These results suggest that the availability of glucose and/or lactate affect the type of death or the survival of primary spermatocytes, where glucose can induce apoptosis, while lactate is a protective factor.

A new perspective on behavioral inconsistency and neural noise in aging: compensatory speeding of neural communication

This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: (1) increased neural noise or random background activity; and (2) slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decreasing nerve conduction velocities leads to a compensatory speeding of neuron firing rates. These increased firing rates lead to a broader distribution of power in the frequency spectrum of neural oscillations, which we propose, can just as easily be interpreted as neural noise. Compensatory speeding of neural activity, as we present, is constrained by the: (A) availability of metabolic energy sources; and (B) competition for frequency bandwidth needed for neural communication. We propose that these constraints lead to the eventual inability to compensate for age-related declines in neural function that are manifested clinically as deficits in cognition, affect, and motor behavior.

Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars

Glucose is an essential source of energy for body metabolism and is transported into cells by glucose transporters (GLUTs). Well-characterized class I GLUT is subdivided into GLUTs1–4, which are selectively expressed depending on tissue glucose requirements. However, there is no available data on the role of GLUTs during tooth development. This study aims to clarify the functional significance of class I GLUT during murine tooth development using immunohistochemistry and an in vitro organ culture experiment with an inhibitor of GLUTs1/2, phloretin, and Glut1 and Glut2 short interfering RNA (siRNA). An intense GLUT1-immunoreaction was localized in the enamel organ of bud-stage molar tooth germs, where the active cell proliferation occurred. By the bell stage, the expression of GLUT1 in the dental epithelium was dramatically decreased in intensity, and subsequently began to appear in the stratum intermedium at the late bell stage. On the other hand, GLUT2-immunoreactivity was weakly observed in the whole tooth germs throughout all stages. The inhibition of GLUTs1/2 by phloretin in the bud-stage tooth germs induced the disturbance of primary enamel knot formation, resulting in the developmental arrest of the explants and the squamous metaplasia of dental epithelial cells. Furthermore, the inhibition of GLUTs1/2 in cap-to-bell-stage tooth germs reduced tooth size in a dose dependent manner. These findings suggest that the expression of GLUT1 and GLUT2 in the dental epithelial and mesenchymal cells seems to be precisely and spatiotemporally controlled, and the glucose uptake mediated by GLUT1 plays a crucial role in the early tooth morphogenesis and tooth size determination.

Training-induced adaptation in purine metabolism in high-level sprinters vs. triathletes

The aim of this study was to assess the effect of training loads on metabolic response of purine derivatives in highly trained sprinters (10 men, age range 20-29 yr) in a 1-yr cycle, compared with endurance-training mode in triathletes (10 men, age range 21-28 yr). A four-time measurement of respiratory parameters, plasma hypoxanthine (Hx) concentration, and erythrocyte hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity was administered in four characteristic training phases (general, specific, competition, and transition). A considerably lower postexercise plasma concentration of Hx in sprinters (8.1-18.0 μmol/l) than in triathletes (14.1-24.9 μmol/l) was demonstrated in all training phases. In both groups, a significant decrease in plasma Hx concentration in the competition phase and a considerable increase in the transition phase were observed. It was found that the resting erythrocyte HGPRT activity increased in the competition period and declined in the transition phase. Sprinters showed higher HGPRT activity (58.5-71.8 nmol IMP·mg Hb(-1)·h(-1)) than triathletes (55.8-66.6 nmol IMP·mg Hb(-1)·h(-1)) in all examinations. The results suggest a more effective use of anaerobic metabolic energy sources induced by sprint training characterized by higher amount of exercise in the anaerobic lactacid and the nonlactacid zone. The changes in plasma Hx concentration and erythrocyte HGPRT activity might serve as sensitive metabolic indicators in the training control, especially in sprint-trained athletes. These parameters may provide information about the energetic status of the muscles in highly trained athletes in which no significant adaptation changes are detected by means of commonly acknowledged biochemical and physiological parameters.

How prokaryotes deal with arsenic†

Arsenic is a notorious poison classified as a carcinogen, a teratogen and a clastogen that ranks number one on the Environmental Protection Agency's priority list of drinking water contaminants. It is ubiquitous and relatively abundant in the Earth's crust. Its mobilization in waters by weathering, volcanic, anthropogenic or biological activities represents a major hazard to public health, exemplified in India and Bangladesh where 50 million people are acutely at risk. Since basically the origin of life, microorganisms have been exposed to this toxic compound and have evolved a variety of resistance mechanisms, such as extracellular precipitation, chelation, intracellular sequestration, active extrusion from the cell or biochemical transformation (redox or methylation). Arsenic efflux systems are widespread and are found in nearly all organisms. Some microorganisms are also able to utilize this metalloid as a metabolic energy source through either arsenite oxidation or arsenate reduction. The energy metabolism involving redox reactions of arsenic has been suggested to have evolved during early life on Earth. This review highlights the different systems evolved by prokaryotes to cope with arsenic and how they participate in its biogeochemical cycle.

QnAs with John P. Grotzinger

QnAs with John P. Grotzinger

The Depolarizing Action of GABA in Cultured Hippocampal Neurons Is Not Due to the Absence of Ketone Bodies

Two recent reports propose that the depolarizing action of GABA in the immature brain is an artifact of in vitro preparations in which glucose is the only energy source. The authors argue that this does not mimic the physiological environment because the suckling rats use ketone bodies and pyruvate as major sources of metabolic energy. Here, we show that availability of physiologically relevant levels of ketone bodies has no impact on the excitatory action of GABA in immature cultured hippocampal neurons. Addition of β-hydroxybutyrate (BHB), the primary ketone body in the neonate rat, affected neither intracellular calcium elevation nor membrane depolarizations induced by the GABA-A receptor agonist muscimol, when assessed with calcium imaging or perforated patch-clamp recording, respectively. These results confirm that the addition of ketone bodies to the extracellular environment to mimic conditions in the neonatal brain does not reverse the chloride gradient and therefore render GABA hyperpolarizing. Our data are consistent with the existence of a genuine “developmental switch” mechanism in which GABA goes from having a predominantly excitatory role in immature cells to a predominantly inhibitory one in adults.

Brain glucose sensing and neural regulation of insulin and glucagon secretion

Glucose homeostasis requires the tight regulation of glucose utilization by liver, muscle and white or brown fat, and glucose production and release in the blood by liver. The major goal of maintaining glycemia at ∼ 5 mM is to ensure a sufficient flux of glucose to the brain, which depends mostly on this nutrient as a source of metabolic energy. This homeostatic process is controlled by hormones, mainly glucagon and insulin, and by autonomic nervous activities that control the metabolic state of liver, muscle and fat tissue but also the secretory activity of the endocrine pancreas. Activation or inhibition of the sympathetic or parasympathetic branches of the autonomic nervous systems are controlled by glucose-excited or glucose-inhibited neurons located at different anatomical sites, mainly in the brainstem and the hypothalamus. Activation of these neurons by hyper- or hypoglycemia represents a critical aspect of the control of glucose homeostasis, and loss of glucose sensing by these cells as well as by pancreatic β-cells is a hallmark of type 2 diabetes. In this article, aspects of the brain-endocrine pancreas axis are reviewed, highlighting the importance of central glucose sensing in the control of counterregulation to hypoglycemia but also mentioning the role of the neural control in β-cell mass and function. Overall, the conclusions of these studies is that impaired glucose homeostasis, such as associated with type 2 diabetes, but also defective counterregulation to hypoglycemia, may be caused by initial defects in glucose sensing.

Cell-based measurements to assess physiological status of Pseudo-nitzschia multiseries, a toxic diatom

Diatoms of the genus Pseudo-nitzschia are potentially toxic microalgae, whose blooms can trigger amnesic shellfish poisoning. The purpose of this study was to test and adapt different probes and procedures in order to assess the physiological status of Pseudo-nitzschia multiseries at the cell level using flow cytometry. To perform these analyses, probes and procedures were first optimized for concentration and incubation time. The percentage of dead Pseudo-nitzschia cells, the metabolic activity of live cells and their intracellular lipid content were then measured following a complete growth cycle. In addition, chlorophyll autofluorescence and efficiency of photosynthesis (quantum yield) were monitored. The concentration and viability of bacteria present in the medium were also assessed. Domoic acid (DA) was quantified as well. Just before the exponential phase, cells exhibited high metabolic activity, but low DA content. DA content per cell became most abundant at the beginning of the exponential phase when lipid storage was high, which provided a metabolic energy source, and when they were surrounded by a high number of bacteria (high bacteria/ P. multiseries ratio). These physiological measurements tended to decrease during exponential phase and until stationary phase, at which time P. multiseries cells did not contain any DA nor store any lipids, and started to die.

Facile Synthesis [5- 13C-4- 2H 2]-L-Glutamine for Hyperpolarized MRS Imaging of Cancer Cell Metabolism

Recent reports suggest that cancer cells may use glutamine, instead of glucose, as an alternative source of metabolic energy. This suggests that hyperpolarized (13)C glutamine may be useful as a magnetic resonance spectroscopy (MRS) imaging agent for detecting changes in glutamine metabolism in cancerous cells or tissues. Synthesis of [5-(13)C-4-(2)H(2)]-L-glutamine was accomplished through a seven-step synthetic pathway with a 44% overall yield. The introduction of two stable isotopes was performed by a NaB(2)H(4)-mixed anhydride reduction and K(13)CN-nuclophilic substitution, respectively. The desired [5-(13)C-4-(2)H(2)]-L-glutamine was successfully obtained by a one-pot reaction of deprotection and controlled cyanide hydrolysis. Hyperpolarized [5-(13)C-4-(2)H(2)]-L-glutamine samples were tested in human glioma cells (myc upregulated glia cells, SF188-Bcl-x(L)). MRS signals were obtained with a 9.4 Tesla 89-mm bore nuclear magnetic resonance spectrometer and a direct-detection multi-nuclear probe. The initial degree of polarization for [5-(13)C-4-(2)H(2)]-L-glutamine was ~5% and the initial (13)C signal to noise ratio was ~100:1. Glutamate was detected within seconds after the injection of hyperpolarized glutamine into the cells. The ratio of glutamate to glutamine was very high, indicating rapid conversion to glutamate. Similar cell uptake studies using [(3)H]-L-glutamine also demonstrated cell uptakes higher than that of [(18)F]fluorodeoxyglucose. We are reporting the first example of using specifically deuterated [5-(13)C-4-(2)H(2)]-L-glutamine in conjunction with hyperpolarized MRS for studying "glutaminolysis" in proliferating tumor cells.

Sucrose transporter NtSUT4 from tobacco BY-2 involved in plant cell shape during miniprotoplast culture

Sucrose plays an important role in several cellular processes since it is a general source of metabolic energy, serves as a precursor for starch and cellulose synthesis, and is a metabolic starting point for carboxylate- and amino acid synthesis. While plant vacuole is the main cellular storage pool, where sucrose accumulates to high concentrations, only a small number of vacuolar sugar transporters have been identified and characterized to date. We initially identified a vacuolar sucrose transporter (NtSUT4) from tobacco BY-2 cells and established transgenic tobacco BY-2 cell lines that overexpress NtSUT4-GFP (BY-SUTG cells). Using a model system for synchronous cell elongation in miniprotoplasts (evacuolated cells) prepared from tobacco BY-2 cells, we found that NtSUT4-GFP overexpression inhibited cell growth towards the cell major axis. Moreover, under the same conditions, we found that the cell walls were well stained by calcofluor in BY-SUTG cells than in wild type BY-2 cells. These results suggest that NtSUT4 is involved in cell shape via sucrose homeostasis in plant cells.

Bacillus subtilis fadB (ysiB) gene encodes an enoyl-CoA hydratase

Fatty acids are essential components of membranes and are an important source of metabolic energy. In bacteria, the β-oxidation pathway is well known in Escherichia coli. Bacillus subtilis possesses a considerable number of genes, organized in five operons, that are most likely involved in the β-oxidation of fatty acids. Among these genes, only one product, FadRBs (YsiA), has been recently characterized as a transcriptional regulatory protein which negatively regulates the expression of β-oxidation genes including those belonging to the lcfA operon, including fadR Bs (ysiA). The probable involvement of the FadRBs (YsiA) regulon members in β-oxidation is inferred from data based on BLASTP similarity of their gene products. In this work, we report the cloning and the expression of B. subtilis fadB Bs(ysiB), belonging to the lcfA operon, and the functional characterization of its product as an enoyl-CoA hydratase, demonstrating the actual involvement of these genes in fatty acid β-oxidation.

Lipid dynamics during early development of Hippocampus guttulatus seahorses: Searching for clues on fatty acid requirements

The biochemical composition of eggs and the nutrient dynamics during early ontogeny can provide better understanding on the nutritional requirements of both broodstock and first-feeding fish, thus constituting a valuable tool for improvement of aquaculture procedures. This study constitutes the first record of lipid composition and fatty acid dynamics during early development of seahorses. Lipid content and fatty acid profile were determined for Hippocampus guttulatus eggs and newborn juveniles, and their patterns of consumption were analyzed during embryonic development. H. guttulatus produced small broods (426 ± 128 juveniles) but invested in the production of large eggs (2.44 ± 0.37 mm) that resulted in large fingerlings (15.53 ± 1.28 mm), which may have a high survival capacity. The total lipid content of seahorse eggs (17.6% DW) was within the typical range of marine fish eggs. Eggs were dominated by PUFA (43.9%), mainly n−3 HUFA (17.4% of DHA and 13.2% of EPA), and showed a lower MUFA content (22.5%). Extremely low AA levels (0.6%) and particularly high EPA concentrations resulted in a low DHA:EPA ratio (1.3) and high EPA:AA (22.3) and n−3:n−6 (12.2) ratios. Fatty acid consumption during embryonic development was considerably high (67.8%), reflecting the high requirements of seahorse embryos. Fatty acids were depleted at different rates, with PUFA being preferentially consumed (75.2%), while SFA were selectively retained (59.2%). PUFA constituted the major source of metabolic energy and the fatty acids 16:0, EPA and DHA were the main fatty acids to fulfill the energetic demands of seahorse embryos. Essential fatty acids (AA, EPA and DHA) were not preferentially retained, with EPA being catabolized at a particularly high rate (88.0%). These patterns of embryonic consumption resulted in newborn juveniles with an exceptionally low lipid content (5.0% DW), a predominance of SFA (41.0%) and extremely low EPA levels (5.0%). Fatty acid composition of H. guttulatus eggs and juveniles provided important clues to determine seahorse requirements, so that suitable feeding protocols could be developed. The use of broodstock and juvenile diets that reflect the lipid profile of eggs will allow the accomplishment of nutritional requirements and improvement of seahorse production.

Effect Of 0.5%Glucose Intake On The Tear Production Of Normoglycemic Emmetropic Nigerians

Glocose the primary source of energy for body's cell metabolism is used up by the body via the activities of insulin that breaks down the glucose into glycogens which is stored up in cells. 0.5% glucose was administered to 50 normoglycemic subjects without fundal or vascular pathology of both sexes with a mean age of 22.27±2.70 years, to determine its effect on tear production. The induced effectswere checkedat 30mins interval till the values approximatedthe normal. The result showed aslight decrease in tear production after 30mins (-1.74mmrepresenting 6.5%). Further decrease was noticed at 60mins -5.32mm(19.78%) andpeak decreasewas observedat 90mins (-7.66mmrepresenting28.48%. It slowly increased towards baseline at 120mins (-5.82mm representing 21.64%), and 150mins (-3.92mm, representing14.57%). This effect was significant (p>0.05) using Z-test statistical analysis. The reduction was observed to be more significant in females than in males probably due to hormonal differences. Exhaustive case history is advocated on patients who report for eye care immediately after feeding on heavy carbohydrate diet at least for the first 90mins as this may reduce tear production leading to apparent dryeyeinorder toguardagainstmisdiagnosis.

Aldose reductase inhibition prevents lipopolysaccharide-induced glucose uptake and glucose transporter 3 expression in RAW264.7 macrophages

Macrophages which play a central role in the injury, infection and sepsis, use glucose as their primary source of metabolic energy. Increased glucose uptake in inflammatory cells is well known to be one of the responsible processes that cause inflammatory response and cytotoxicity. We have shown recently that the inhibition of aldose reductase (AR) prevents bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in macrophages. However, it is not known how AR inhibition prevents LPS-induced inflammation. Here in, we examined the effect of AR inhibition on LPS-induced glucose uptake and the expression of glucose transporter 3 (GLUT-3) in RAW264.7 murine macrophages. Stimulation of macrophages with LPS-increased glucose uptake as measured by using C 14 labeled methyl- d-glucose and inhibition of AR prevented it. Similarly, ablation of AR by using AR-siRNA also prevented the LPS-induced glucose uptake in macrophages. Further, AR inhibition also prevented the LPS-induced up-regulation of GLUT-3 expression, cyclic adenosine monophosphate (cAMP) accumulation and protein kinase A (PKA) activation in RAW264.7 cells. Moreover, LPS-induced down-regulation of cAMP response element modulator (CREM), phosphorylation of cAMP response element-binding protein (CREB) and DNA-binding of CREB were also prevented by AR inhibition. Further, inhibition of AR or PKA also prevented the LPS-induced levels of GLUT-3 protein as well as mRNA in macrophages. These results indicate that AR mediates LPS-induced glucose uptake and expression of glucose transporter-3 via cAMP/PKA/CREB pathway and thus represents a novel mechanism by which AR regulates LPS-induced inflammation.