Regulation Of Metabolic Responses Research Articles

Differential AMPK-mediated metabolic regulation observed in hibernation-style polymorphisms in Siberian chipmunks.

Hibernation is a unique physiological phenomenon allowing extreme hypothermia in endothermic mammals. Hypometabolism and hypothermia tolerance in hibernating animals have been investigated with particular interest; recently, studies of cultured cells and manipulation of the nervous system have made it possible to reproduce physiological states related to hypothermia induction. However, much remains unknown about the periodic regulation of hibernation. In particular, the physiological mechanisms facilitating the switch from an active state to a hibernation period, including behavioral changes and the acquisition of hypothermia tolerance remain to be elucidated. AMPK is a protein known to play a central role not only in feeding behavior but also in metabolic regulation in response to starvation. Our previous research has revealed that chipmunks activate AMPK in the brain during hibernation. However, whether AMPK is activated during winter in non-hibernating animals is unknown. Previous comparative studies between hibernating and non-hibernating animals have often been conducted between different species, consequently it has been impossible to account for the effects of phylogenetic differences. Our long-term monitoring of siberian chipmunks, has revealed intraspecific variation between those individuals that hibernate annually and those that never become hypothermic. Apparent differences were found between hibernating and non-hibernating types with seasonal changes in lifespan and blood HP levels. By comparing seasonal changes in AMPK activity between these polymorphisms, we clarified the relationship between hibernation and AMPK regulation. In hibernating types, phosphorylation of p-AMPK and p-ACC was enhanced throughout the brain during hibernation, indicating that AMPK-mediated metabolic regulation is activated. In non-hibernating types, AMPK and ACC were not seasonally activated. In addition, AMPK activation in the hypothalamus had already begun during high Tb before hibernation. Changes in AMPK activity in the brain during hibernation may be driven by circannual rhythms, suggesting a hibernation-regulatory mechanism involving AMPK activation independent of Tb. The differences in brain AMPK regulation between hibernators and non-hibernators revealed in this study were based on a single species thus did not involve phylogenetic differences, thereby supporting the importance of brain temperature-independent AMPK activation in regulating seasonal metabolism in hibernating animals.

Integration of Transcriptomic and Metabolomic Profiles Provides Insights into the Influence of Nitrogen on Secondary Metabolism in Fusarium sacchari.

Nitrogen availability might play an essential role in plant diseases by enhancing fungal cell growth and influencing the expression of genes required for successful pathogenesis. Nitrogen availability could modulate secondary metabolic pathways as evidenced by the significant differential expression of several core genes involved in mycotoxin biosynthesis and genes encoding polyketide synthase/nonribosomal peptide synthetases, cytochrome P450 and carbohydrate-active enzymes in Fusarium sacchari, grown on different nitrogen sources. A combined analysis was carried out on the transcript and metabolite profiles of regulatory metabolic processes and the virulence of Fusarium sacchari grown on various nitrogen sources. The nitrogen regulation of the gibberellin gene cluster included the metabolic flux and multiple steps of gibberellin synthesis. UHPLC-MS/MS-based metabolome analysis revealed the coordination of these related transcripts and the accumulation of gibberellin metabolites. This integrated analysis allowed us to uncover additional information for a more comprehensive understanding of biological events relevant to fungal secondary metabolic regulation in response to nitrogen availability.

DNA hypermethylation of Kiss1r promoter and reduction of hepatic Kiss1r in female rats with type 2 diabetes

ABSTRACT Kisspeptin, produced from the brain and peripheral tissues, may constitute an important link in metabolic regulation in response to external cues, such as diet. The kisspeptin system is well described in the brain. However, its function and regulation in the peripheral tissues, especially in relation to metabolic disease and sex differences, remain to be elucidated. As Kiss1 and Kiss1r, encoding for kisspeptin and kisspeptin receptors, respectively, are altered by overnutrition/fasting and regulated by DNA methylation during puberty and cancer, epigenetic mechanisms in metabolic disorders are highly probable. In the present study, we experimentally induced type 2 diabetes mellitus (DM2) in female Wistar rats using high-fat diet/streptozocin. We analysed expression and DNA methylation of Kiss1 and Kiss1r in the peripheral tissues, using quantitative-reverse-transcription PCR (qRT-PCR) and pyrosequencing. We discovered differential expression of Kiss1 and Kiss1r in peripheral organs in DM2 females, as compared with healthy controls, and the profile differed from patterns reported earlier in males. DM2 in females was linked to the increased Kiss1 mRNA in the liver and increased Kiss1r mRNA in the liver and adipose tissue. However, Kiss1r promoter was hypermethylated in the liver, suggesting gene silencing. Indeed, the increase in DNA methylation of Kiss1r promoter was accompanied by a reduction in Kiss1r protein, implying epigenetic or translational gene repression. Our results deliver novel evidence for tissue-specific differences in Kiss1 and Kiss1r expression in peripheral organs in DM2 females and suggest DNA methylation as a player in regulation of the hepatic kisspeptin system in DM2.

Silencing of hypothalamic FGF11 prevents diet-induced obesity

Fibroblast growth factor 11 (FGF11) is a member of the intracellular fibroblast growth factor family. Here, we report the central role of FGF11 in the regulation of metabolism. Lentiviral injection of Fgf11 shRNA into the arcuate nucleus of the mouse hypothalamus decreased weight gain and fat mass, increased brown adipose tissue thermogenesis, and improved glucose and insulin intolerances under high-fat diet conditions. Fgf11 was expressed in the NPY–expressing neurons, and Fgf11 knockdown considerably decreased Npy expression and projection, leading to increased expression of tyrosine hydroxylase in the paraventricular nucleus. Mechanistically, FGF11 regulated Npy gene expression through the glycogen synthase kinase 3–cAMP response element-binding protein pathway. Our study defines the physiological significance of hypothalamic FGF11 in the regulation of metabolism in response to overnutrition such as high-fat diet.

Transcriptomics and Metabolomics Analyses Reveal Defensive Responses and Flavonoid Biosynthesis of Dracaena cochinchinensis (Lour.) S. C. Chen under Wound Stress in Natural Conditions.

Dracaena cochinchinensis has special defensive reactions against wound stress. Under wound stress, D. cochinchinensis generates a resin that is an important medicine known as dragon’s blood. However, the molecular mechanism underlying the defensive reactions is unclear. Metabolomics and transcriptomics analyses were performed on stems of D. cochinchinensis at different timepoints from the short term to the long term after wounding. According to the 378 identified compounds, wound-induced secondary metabolic processes exhibited three-phase characteristics: short term (0–5 days), middle term (10 days–3 months), and long term (6–17 months). The wound-induced transcriptome profile exhibited characteristics of four stages: within 24 h, 1–5 days, 10–30 days, and long term. The metabolic regulation in response to wound stress mainly involved the TCA cycle, glycolysis, starch and sucrose metabolism, phenylalanine biosynthesis, and flavonoid biosynthesis, along with some signal transduction pathways, which were all well connected. Flavonoid biosynthesis and modification were the main reactions against wound stress, mainly comprising 109 flavonoid metabolites and 93 wound-induced genes. A group of 21 genes encoding CHS, CHI, DFR, PPO, OMT, LAR, GST, and MYBs were closely related to loureirin B and loureirin C. Wound-induced responses at the metabolome and transcriptome level exhibited phase characteristics. Complex responses containing primary metabolism and flavonoid biosynthesis are involved in the defense mechanism against wound stress in natural conditions, and flavonoid biosynthesis and modification are the main strategies of D. cochinchinensis in the long-term responses to wound stress.

Red light-transmittance bagging promotes carotenoid accumulation of grapefruit during ripening

Light, a crucial environmental signal, is involved in the regulation of secondary metabolites. To understand the mechanism by which light influences carotenoid metabolism, grapefruits were bagged with four types of light-transmitting bags that altered the transmission of solar light. We show that light-transmitting bagging induced changes in carotenoid metabolism during fruit ripening. Compared with natural light, red light (RL)-transmittance treatment significantly increases the total carotenoid content by 62%. Based on weighted gene co-expression network analysis (WGCNA), ‘blue’ and ‘turquoise’ modules are remarkably associated with carotenoid metabolism under different light treatment (p < 0.05). Transcriptome analysis identifies transcription factors (TFs) bHLH128, NAC2-like/21/72, MYB-like, AGL11/AGL61, ERF023/062, WRKY20, SBPlike-7/13 as being involved in the regulation of carotenoid metabolism in response to RL. Under RL treatment, these TFs regulate the accumulation of carotenoids by directly modulating the expression of carotenogenic genes, including GGPPS2, PDS, Z-ISO, ZDS2/7, CRTISO3, CYP97A, CHYB, ZEP2, CCD1-2. Based on these results, a network of the regulation of carotenoid metabolism by light in citrus fruits is preliminarily proposed. These results show that RL treatments have great potential to improve coloration and nutritional quality of citrus fruits.

Overexpression of translationally controlled tumor protein ameliorates metabolic imbalance and increases energy expenditure in mice

Background/ObjectivesTranslationally controlled tumor protein (TCTP) exhibits numerous biological functions. It has been shown to be involved in the regulation of glucose. However, its specific role in metabolism has not yet been clearly elucidated. Here, we aimed to assess the effect of TCTP overexpression on metabolic tissues and systemic energy metabolism.Subjects/MethodsWe investigated whether TCTP can ameliorate the metabolic imbalance that causes obesity using TCTP-overexpressing transgenic (TCTP TG) mice. The mice were subjected to biochemical, morphological, physiological and protein expression studies to define the role of TCTP in metabolic regulation in response to normal chow diet (NCD) compared to high-fat diet (HFD) conditions, and cold environment.ResultsWe found that TCTP TG mice show improved metabolic homeostasis under both of NCD and HFD conditions with simultaneous enhancements in glucose tolerance and insulin sensitivity. In particular, we found coincident increases in energy expenditure with significant upregulation of uncoupling protein 1 (UCP1) in the brown adipose tissue (BAT). Moreover, TCTP overexpressing mice exhibit significantly enhanced adaptive thermogenesis of BAT in response to cold exposure.ConclusionsOverexpression of TCTP ameliorated systemic metabolic homeostasis by stimulating UCP1-mediated thermogenesis in the BAT. This suggests that TCTP may function as a modulator of energy expenditure. This study suggests TCTP may serve as a therapeutic target for obesity and obesity-associated metabolic disorders including type 2 diabetes.

Liver Transcriptome Responses to Heat Stress and Newcastle Disease Virus Infection in Genetically Distinct Chicken Inbred Lines.

Heat stress results in reduced productivity, anorexia, and mortality in chickens. The objective of the study was to identify genes and signal pathways associated with heat stress and Newcastle disease virus (NDV) infection in the liver of chickens through RNA-seq analysis, using two highly inbred chicken lines (Leghorn and Fayoumi). All birds were held in the same environment until 14 days of age. On day 14, half the birds were exposed to 38 °C with 50% relative humidity for 4 h, then 35 °C until the end of the experiment. The remaining birds were kept at 25 °C throughout the experiment. The heat-treated birds were inoculated at 21 days of age with 107 EID50 (One EID50 unit is the amount of virus that will infect 50 percent of inoculated embryos) NDV La Sota strain to investigate the effects of both heat stress and NDV infection. Physiological parameters were recorded as blood phenotypes at three stages: acute heat (AH), chronic heat (CH1), and chronic heat combined with NDV infection (CH&NDV), at 4 h, 7 days, and 10 days post-initiation of heat treatment, respectively. Our previous work revealed that the heat-resilient Fayoumi line maintained a more stable acid-base balance in their blood compared to the Leghorn line. Liver samples were harvested on both AH and CH&NDV to characterize the transcriptome profiles of these two inbred lines. Both genetic lines and treatments had large impact on the liver transcriptome. Fayoumi birds had more differentially expressed genes (DEGs) than Leghorn birds for both treatments. Metabolic and immune-related genes were on the DEG list, with Fayoumi having more immune-related DEGs than Leghorns, which was confirmed by gene functional enrichment analysis. Weighted correlation network analysis (WGCNA) indicated that the driver genes such as Solute Carrier Family genes could be very important for stabilizing the acid-base balance in Fayoumi birds during heat stress. Therefore, candidate genes such solute carrier family genes could be potential genetic targets that are regulated by Fayoumis to maintain physical hemostasis under heat stress. Differential gene expression showed that Leghorns mainly performed metabolic regulation in response to heat stress and NDV infection, while Fayoumis regulated both immune and metabolic functions. This study provides novel insights and enhances our understandings of liver response to heat stress of heat resilient and susceptible inbred chicken lines.

Photosynthetic Carbon Partitioning and Metabolic Regulation in Response to Very-Low and High CO2 in Microchloropsis gaditana NIES 2587.

Photosynthetic organisms fix inorganic carbon through carbon capture machinery (CCM) that regulates the assimilation and accumulation of carbon around ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). However, few constraints that govern the central carbon metabolism are regulated by the carbon capture and partitioning machinery. In order to divert the cellular metabolism toward lipids and/or biorenewables it is important to investigate and understand the molecular mechanisms of the CO2-driven carbon partitioning. In this context, strategies for enhancement of CO2 fixation which will increase the overall biomass and lipid yields, can provide clues on understanding the carbon assimilation pathway, and may lead to new targets for genetic engineering in microalgae. In the present study, we have focused on the physiological and metabolomic response occurring within marine oleaginous microalgae Microchloropsis gaditana NIES 2587, under the influence of very-low CO2 (VLC; 300 ppm, or 0.03%) and high CO2 (HC; 30,000 ppm, or 3% v/v). Our results demonstrate that HC supplementation in M. gaditana channelizes the carbon flux toward the production of long chain polyunsaturated fatty acids (LC-PUFAs) and also increases the overall biomass productivities (up to 2.0 fold). Also, the qualitative metabolomics has identified nearly 31 essential metabolites, among which there is a significant fold change observed in accumulation of sugars and alcohols such as galactose and phytol in VLC as compared to HC. In conclusion, our focus is to understand the entire carbon partitioning and metabolic regulation within these photosynthetic cell factories, which will be further evaluated through multiomics approach for enhanced productivities of biomass, biofuels, and bioproducts (B3).

How to catch a HIF-the work of Gregg Semenza's lab on hypoxia-inducible factor 1.

How to catch a HIF-the work of Gregg Semenza's lab on hypoxia-inducible factor 1.

ROS and pentose phosphate pathway: mathematical modelling of the metabolic regulation in response to xenobiotic-induced oxidative stress and the proposed Impact of the gluconate shunt

Elevated intracellular levels of reactive oxygen species (ROS), e.g. resulting from exposure to xenobiotics, can cause severe damages. Antioxidant defence mechanisms, which involve regulation of enzyme activities, protect cells to a certain extent. Nevertheless, continuous or increased exposure can overwhelm this system resulting in an adverse cellular state. To simulate exposure scenarios and to investigate the transition to an adverse cellular state, a mathematical model for the dynamics of ROS in response to xenobiotic-induced oxidative stress has been developed. It is based on exposure experiments of human urothelial cells (RT4) to the nitrated polycyclic aromatic hydrocarbon 3-nitrobenzanthrone (3-NBA), a component of diesel engine exhaust, and takes into account the following metabolic pathways of the antioxidant defence system: glutathione redox cycle scavenging directly ROS, the pentose phosphate pathway and the gluconate shunt as NADPH supplier and the beginning of glycolysis. In addition, ROS generation due to the bioactivation of 3-NBA has been implemented. The regulation of enzyme activities plays an important role in the presented mathematical model. The in silico model consists of ordinary differential equations on the basis of enzyme kinetics and mass action for the metabolism of 3-NBA. Parameters are either estimated from performed in vitro experiments via least-squares fitting or obtained from the literature. The results underline the importance of the pentose phosphate pathway to cope with oxidative stress and suggest an important role of the gluconate shunt during low-dose exposure.

An integrated metabolomic and gene expression analysis identifies heat and calcium metabolic networks underlying postharvest sweet cherry fruit senescence.

Ηeat and calcium treatments reprogram sweet cherry fruit metabolism during postharvest senescence as evidenced by changes in respiration, amino acid metabolism, sugars, and secondary metabolites shift. Heat and calcium treatments are used to improvepostharvest fruit longevity; however, the exact mechanism remains poorly understood. To characterize the impact of these treatments on sweet cherries metabolism, 'Lapins' fruits were treated with heat or CaCl2 solutions and their combination and subsequently were exposed at room temperature, for up to 4days, defined as senescence period. Single and combined heat and calcium treatments partially delayed fruit senescence, as evidenced by changes in fruit colour darkening, skin penetration force, and respiration activity. Calcium content was noticeably increased by heat in Ca-treated fruit. Several primary metabolites, including amino acids, organic acids, and alcohols, were decreased in response to both treatments, while many soluble sugars and secondary metabolites were increased within 1day post-treatment.Changes of several metabolites in heat-treated fruits, especially esculetin, peonidin 3-O-glucoside and peonidin 3-O-galactoside, ribose, pyroglutamate, and isorhamnetin-3-O-rutinoside, were detected. The metabolome of fruit exposed to calcium also displayed substantial modulations, particularly in the levels of galactose, glycerate, aspartate, tryptophan, phospharate rutin, and peonidin 3-O-glucoside. The expression of several genes involved in TCA cycle (MDH1, IDH1, OGDH, SUCLA2, and SDH1-1), pectin degradation (ADPG1) as well as secondary (SK1, 4CL1, HCT, and BAN), amino acids (ALDH18A1, ALDH4A1, GS, GAD, GOT2, OPLAH, HSDH, and SDS), and sugar (PDHA1 and DLAT) metabolism were affected by both treatments. Pathway-specific analysis further revealed the regulation of fruit metabolic programming by heat and calcium. This work provides a comprehensive understanding of metabolic regulation in response to heat and calcium during fruit senescence.

Effects of Statins on Gut Microbiota (Microbiome)

Statins are the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A, which are extensively used to decrease the concentration of cholesterol in patients with hyperlipidemia. Statins are divided into two categories based on their own unique properties. Considering the pleiotropic effects of statins, they are applied as antioxidant, anti-inflammatory, anti-thrombotic, immunomodulatory, and plaque-stabilizing agents. In addition, statins affect the diversity and population of gut microbiota, which is a complicated microbial community remarkably involved in the regulation of metabolic responses, immune system, and human health. This community is also associated with age-related health problems, allergy, asthma, and inflammatory intestinal diseases. Therefore, evaluation of the interactions between statins and gut microbiota is essential to predicting the outcomes of these agents. The present study aimed to review the properties and pleiotropic effects of statins. Furthermore, the role of gut microbiota in health was discussed, and the significant effects of statins on gut microbiota and their interactions were described based on clinical and animal studies.

Physiological and biochemical responses of Eucalyptus seedlings to hypoxia

Hypoxia promoted distinct changes in the levels of hormones, amino acids and organic acids in the roots and shoots of a seedling from 2 Eucalyptus clones. These results indicate that modulation of hormone production, as well as specific chemical constituents associated with primary metabolism, contributes to the regulation of growth of Eucalyptus seedlings under hypoxic conditions. Although floods in areas under Eucalyptus cultivation in Brazil negatively affect plant growth, chemical markers and/or indicators of hypoxia contributes to the regulation.s This study aimed to evaluate the hormonal and metabolic alterations induced by hypoxia on seedling growth. Seedlings of Eucalyptus urograndis clones VCC 975 and 1004 were grown in liquid solution and submitted to bubbling with air or with nitrogen. Levels of indol-3-acetic acid (IAA), abscisic acid (ABA), ethylene, 1-aminocyclopropane-1-carboxylic acid (ACC), primary metabolite profile and photosynthetic parameters were evaluated after fourteen days. Hypoxia did not affect shoot dry mass of the seedlings. However, it decreased stomatal conductance and photosynthetic CO2 assimilation rate, and increased levels of ABA in the shoot. Hypoxia greatly reduced the dry mass and volume of roots, concomitantly with higher ACC and ethylene production. Moreover, hypoxia promoted distinct changes in IAA levels, and in amino acid and organic acid metabolism in roots and shoots. The biosynthesis of ABA, ethylene and IAA and its quantity in root tissues indicates the regulation of metabolism in response to hypoxia in Eucalyptus clones.

Homeostatic Role of Autophagy in Hepatocytes.

Autophagy actively participates in the physiological process of the liver. While the direct effect of autophagy may be limited to the sequestration and degradation of a selective cargo, its overall impact can be broad, affecting many more physiological processes regulated by the particular cargo. This review will discuss two aspects of the importance of autophagy in the liver: metabolic regulation in response to feeding and starvation, and pathological consequences in the absence of autophagy. These two aspects illustrate the homeostatic functions of autophagy in the liver, one in a more direct fashion, regulating the cellular nutrient supply, and the other in a more indirect fashion, controlling the pathological signaling triggered by the abnormal accumulation of cargos. Remarkably, the hepatic pathology in autophagy-deficient livers does not seem different from that presented in other chronic liver diseases. Autophagy deficiency can be a model for the study of the relevant molecular mechanisms.

Lysine propionylation modulates the transcriptional activity of phosphate regulator PhoP in Saccharopolyspora erythraea.

Phosphate concentration extensively modulates the central physiological processes mediated by the two-component system PhoR-PhoP in actinobacteria. The system serves a role beyond phosphate metabolism, mediating crucial functions in nitrogen and carbon metabolism, and secondary metabolism in response to the nutritional states. Here, we found that the phosphate-sensing regulator PhoP was propionylated, and thus lost its DNA-binding activity in vivo and in vitro in Saccharopolyspora erythraea. Two key conserved lysine residues 198 and 203 (K198 and K203) in winged HTH motif at the C-terminal domain of PhoP are propionylated by protein acyltransferase AcuA (encoding by sace_5148). Single amino acid mutation of these two lysine residues resulted in severely impaired binding of PhoP to PHO box. The addition of propionate (to supply precursors for erythromycin biosynthesis) increases the intracellular propionylation level of PhoP, resulting in the loss of response to phosphate availability. Furthermore, simultaneous mutation of K198 and K203 of PhoP to arginine, mimicking the non-propionylated form, promotes the expression of the PhoP regulon under the condition of propionate addition. Together, these findings present a common regulatory mechanism of genes' expression mediated by posttranslational regulation of OmpR family transcriptional regulator PhoP and provide new insights into the multifaceted regulation of metabolism in response to nutritional signals.

Regulation of phytochemicals in fruits and berries by environmental variation-Sugars and organic acids.

Sugars and organic acids are important phytochemicals contributing to the nutrition and sensory properties of fruits and berries. Their contents are closely correlated to the genetic background of plants as well as to the environmental conditions during growth. This review focuses on the recent researches on the metabolism of these compounds in fruits and berries in response to the variation of environmental conditions, including temperature, radiation, and water supply. A great deal of investigations indicates that the influence of environmental factors on the composition of fruits/berries depended largely on the genetic background. Moreover, the metabolic regulation in response to environmental changes also varies between different plant developmental stages. Nevertheless, some general trends, like the positive correlation between light intensity and sugar content, were observed in most investigations. In grapes (Vitis vinifera L.), the content of malic acid always decreases as light intensity increases, and as the water supply decreases. PRACTICAL APPLICATIONS: The contents of sugars and organic acids, and especially their relative ratio, are important indicators determining the taste and quality of fruits and fruit products. In this review, we summarized the investigations carried out on the regulation of these sensory contributing primary metabolites in fruits and berries in relation to the variation of environmental conditions. It was indicated that various factors, such as plant genotype, growing period, and interaction between environmental factors, might contribute to the impact of environmental changes on the composition of fruits/berries. The article not only provides comprehensive knowledges in food chemistry and plant physiology but also provide important background knowledge for berry cultivation and breeding, as well as useful guidelines for utilization of fruits and berries in food industry.

Cerebral Hyperperfusion and Metabolic Regulation in Response to Hypoxia: Do ATP‐Sensitive Potassium Channels Play a Role?

ATP‐sensitive K+ channels (K+ATP) mediate hypoxia‐induced cerebral vasodilatation and hyperperfusion in animals, a compensatory mechanism that maintains the oxidative metabolic stability of the brain. We then tested whether K+ATP blockade attenuates the increase in cerebral blood flow (CBF) in humans and leads to a shift towards brain non‐oxidative metabolism during isocapnic hypoxia (IH). Seven men (25 ± 4 yrs.) were exposed to 5‐min of normoxia and IH (10% O2) before (BG) and 3 h after Glibenclamide oral administration (AG – 5 mg). Invasive mean arterial pressure (MAP), radial artery and right jugular venous blood saturation, oxygen (PO2) and carbon dioxide (PCO2) partial pressure, glucose and lactate levels, and internal carotid (ICA) and vertebral (VA) artery blood flow (BF, Doppler ultrasound) were quantified over the last 30 s. In another protocol, 5 male subjects (24 ± 4 yrs.) underwent the same procedures before (BPL) and 3 h after placebo ingestion (APL – 5 mg of starch). CBF ((ICA BF + VA BF)×2 (mL/min)), cerebral metabolic rate of O2 (CMRO2), oxygen‐glucose (OGI) and oxygen‐carbohydrate (OCI) indexes were determined in each trial. IH provoked similar arterial desaturation (ΔBG −18.3 ± 6.0 vs. ΔAG −17.9 ± 3.5%, p = 0.784) and PaO2 reduction (ΔBG −80.6 ± 4.8 vs. ΔAG −77.6 ± 9.0 mmHg, p = 0.351). MAP and PaCO2 remained unchanged under both conditions. Smaller increases in ICA (ΔBG +111 ± 94 vs. ΔAG +66 ± 68 mL/min, p = 0.021) and VA BF (ΔBG +44 ± 38 vs. ΔAG +26 ± 39 mL/min, p=0.035) were observed under K+ATP blockade. IH‐induced increase in CBF (ΔBG +310 ± 215 vs. ΔAG +184 ± 150 mL/min, p = 0.017) was attenuated and followed by a smaller increase in CMRO2 (ΔBG +18.9 ± 14.8 vs. ΔAG +4.5 ± 12.2 mmol/100 g/min, p = 0.015). There was no IH‐induced shift to cerebral non‐oxidative metabolism as OGI and OCI did not change. CBF and metabolic responses to IH did not differ between BPL and APL. Therefore, our findings indicate that K+ATP play a role in the human cerebral hyperemia and maintenance of the brain metabolic stability during isocapnic hypoxia.Support or Funding InformationCNPq, CAPES, FAPERJ, FINEPThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Transcriptome analysis reveals metabolic alteration due to consecutive monoculture and abiotic stress stimuli in Rehamannia glutinosa Libosch.

We deeply investigated the mechanism underlying metabolic regulation in response to consecutive monoculture (replanting disease) and different abiotic stresses that unfolded the response mechanism to consecutive monoculture problem through RNA-seq analysis. The consecutive monoculture problem (CMP) resulted of complex environmental stresses mediated by multiple factors. Previous studies have noted that multiple stress factors in consecutive monoculture soils or plants severely limited the interpretation of the critical molecular mechanism, and made a predict that the specifically responding factor was autotoxic allelochemicals. To identify the specifically responding genes, we compared transcriptome changes in roots of Rehamannia glutinosa Libosch using consecutive monoculture, salt, drought, and ferulic acid as stress factors. Comparing with normal growth, 2502, 2672, 2485, and 1956 genes were differentially expressed in R. glutinosa under consecutive monoculture practice, salt, drought, and ferulic acid stress, respectively. In addition, 510 genes were specifically expressed under consecutive monoculture, which were not present under the other stress conditions. Integrating the biological and enrichment analyses of the differentially expressed genes, the result demonstrated that the plants could alter enzyme genes expression to reconstruct the complicated metabolic pathways, which used to tolerate the CMP and abiotic stresses. Furthermore, most of the affected pathway genes were closely related to secondary metabolic processes, and the influence of consecutive monoculture practice on the transcriptome genes expression profile was very similar to the profile under salt stress and then to the profile under drought stress. The outlined schematic diagram unfolded the putative signal regulation mechanism in response to the CMP. Genes that differentially up- or down-regulated under consecutive monoculture practice may play important roles in the CMP or replanting disease in R. glutinosa.

Plant GABA: Not Just a Metabolite.

γ-Aminobutyric acid (GABA) accumulates rapidly when plants are exposed to stress. Whether GABA accumulation represents the regulation of metabolism in response to stress or an adaptive response to mitigate stress is unknown. Genetic manipulation of GABA levels has revealed that GABA accumulation functions in defense against drought and insect herbivory.