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Sample records for regulates hepatic energy

  1. Hepatic protein phosphatase 1 regulatory subunit 3B (Ppp1r3b) promotes hepatic glycogen synthesis and thereby regulates fasting energy homeostasis.

    Science.gov (United States)

    Mehta, Minal B; Shewale, Swapnil V; Sequeira, Raymond N; Millar, John S; Hand, Nicholas J; Rader, Daniel J

    2017-06-23

    Maintenance of whole-body glucose homeostasis is critical to glycemic function. Genetic variants mapping to chromosome 8p23.1 in genome-wide association studies have been linked to glycemic traits in humans. The gene of known function closest to the mapped region, PPP1R3B (protein phosphatase 1 regulatory subunit 3B), encodes a protein (G L ) that regulates glycogen metabolism in the liver. We therefore sought to test the hypothesis that hepatic PPP1R3B is associated with glycemic traits. We generated mice with either liver-specific deletion ( Ppp1r3b Δ hep ) or liver-specific overexpression of Ppp1r3b The Ppp1r3b deletion significantly reduced glycogen synthase protein abundance, and the remaining protein was predominantly phosphorylated and inactive. As a consequence, glucose incorporation into hepatic glycogen was significantly impaired, total hepatic glycogen content was substantially decreased, and mice lacking hepatic Ppp1r3b had lower fasting plasma glucose than controls. The concomitant loss of liver glycogen impaired whole-body glucose homeostasis and increased hepatic expression of glycolytic enzymes in Ppp1r3b Δ hep mice relative to controls in the postprandial state. Eight hours of fasting significantly increased the expression of two critical gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, above the levels in control livers. Conversely, the liver-specific overexpression of Ppp1r3b enhanced hepatic glycogen storage above that of controls and, as a result, delayed the onset of fasting-induced hypoglycemia. Moreover, mice overexpressing hepatic Ppp1r3b upon long-term fasting (12-36 h) were protected from blood ketone-body accumulation, unlike control and Ppp1r3b Δ hep mice. These findings indicate a major role for Ppp1r3b in regulating hepatic glycogen stores and whole-body glucose/energy homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2.

    Science.gov (United States)

    Scapa, Erez F; Pocai, Alessandro; Wu, Michele K; Gutierrez-Juarez, Roger; Glenz, Lauren; Kanno, Keishi; Li, Hua; Biddinger, Sudha; Jelicks, Linda A; Rossetti, Luciano; Cohen, David E

    2008-07-01

    Phosphatidylcholine transfer protein (PC-TP, also known as StarD2) is a highly specific intracellular lipid binding protein with accentuated expression in oxidative tissues. Here we show that decreased plasma concentrations of glucose and free fatty acids in fasting PC-TP-deficient (Pctp(-/-)) mice are attributable to increased hepatic insulin sensitivity. In hyperinsulinemic-euglycemic clamp studies, Pctp(-/-) mice exhibited profound reductions in hepatic glucose production, gluconeogenesis, glycogenolysis, and glucose cycling. These changes were explained in part by the lack of PC-TP expression in liver per se and in part by marked alterations in body fat composition. Reduced respiratory quotients in Pctp(-/-) mice were indicative of preferential fatty acid utilization for energy production in oxidative tissues. In the setting of decreased hepatic fatty acid synthesis, increased clearance rates of dietary triglycerides and increased hepatic triglyceride production rates reflected higher turnover in Pctp(-/-) mice. Collectively, these data support a key biological role for PC-TP in the regulation of energy substrate utilization.

  3. Functional proteomic analysis of corticosteroid pharmacodynamics in rat liver: Relationship to hepatic stress, signaling, energy regulation, and drug metabolism.

    Science.gov (United States)

    Ayyar, Vivaswath S; Almon, Richard R; DuBois, Debra C; Sukumaran, Siddharth; Qu, Jun; Jusko, William J

    2017-05-08

    Corticosteroids (CS) are anti-inflammatory agents that cause extensive pharmacogenomic and proteomic changes in multiple tissues. An understanding of the proteome-wide effects of CS in liver and its relationships to altered hepatic and systemic physiology remains incomplete. Here, we report the application of a functional pharmacoproteomic approach to gain integrated insight into the complex nature of CS responses in liver in vivo. An in-depth functional analysis was performed using rich pharmacodynamic (temporal-based) proteomic data measured over 66h in rat liver following a single dose of methylprednisolone (MPL). Data mining identified 451 differentially regulated proteins. These proteins were analyzed on the basis of temporal regulation, cellular localization, and literature-mined functional information. Of the 451 proteins, 378 were clustered into six functional groups based on major clinically-relevant effects of CS in liver. MPL-responsive proteins were highly localized in the mitochondria (20%) and cytosol (24%). Interestingly, several proteins were related to hepatic stress and signaling processes, which appear to be involved in secondary signaling cascades and in protecting the liver from CS-induced oxidative damage. Consistent with known adverse metabolic effects of CS, several rate-controlling enzymes involved in amino acid metabolism, gluconeogenesis, and fatty-acid metabolism were altered by MPL. In addition, proteins involved in the metabolism of endogenous compounds, xenobiotics, and therapeutic drugs including cytochrome P450 and Phase-II enzymes were differentially regulated. Proteins related to the inflammatory acute-phase response were up-regulated in response to MPL. Functionally-similar proteins showed large diversity in their temporal profiles, indicating complex mechanisms of regulation by CS. Clinical use of corticosteroid (CS) therapy is frequent and chronic. However, current knowledge on the proteome-level effects of CS in liver and

  4. Transcriptional regulation of hepatic lipogenesis.

    Science.gov (United States)

    Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

    2015-11-01

    Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

  5. Autonomic regulation of hepatic glucose production.

    Science.gov (United States)

    Bisschop, Peter H; Fliers, Eric; Kalsbeek, Andries

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system to communicate with peripheral organs. Within the brain, the hypothalamus is the key region to integrate signals on energy status, including signals from lipid, glucose, and hormone sensing cells, with afferent neural signals from the internal and external milieu. In turn, the hypothalamus regulates metabolism in peripheral organs, including the liver, not only via the anterior pituitary gland but also via multiple neuropeptidergic pathways in the hypothalamus that have been identified as regulators of hepatic glucose metabolism. These pathways comprise preautonomic neurons projecting to nuclei in the brain stem and spinal cord, which relay signals from the hypothalamus to the liver via the autonomic nervous system. The neuroendocrine and neuronal outputs of the hypothalamus are not separate entities. They appear to act as a single integrated regulatory system, far more subtle, and complex than when each is viewed in isolation. Consequently, hypothalamic regulation should be viewed as a summation of both neuroendocrine and neural influences. As a result, our endocrine-based understanding of diseases such as diabetes and obesity should be expanded by integration of neural inputs into our concept of the pathophysiological process. © 2014 American Physiological Society.

  6. PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism

    NARCIS (Netherlands)

    Diepen, van J.A.; Jansen, P.A.; Ballak, D.B.; Hijmans, A.; Hooiveld, G.J.E.J.; Rommelaere, S.; Kersten, A.H.; Stienstra, R.

    2014-01-01

    Background & Aims Peroxisome proliferator-activated receptor alpha (PPARa) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARa target gene in liver, but its function in hepatic lipid metabolism is unknown.

  7. Atomic Energy Control Regulations

    International Nuclear Information System (INIS)

    1992-01-01

    This is the consolidated text of the Atomic Energy Control Regulations of 17 March 1960, with amendments to 27 August 1992. The Regulations cover the licensing of nuclear facilities, radiation sources, including uranium mining, radiation protection questions, etc. (NEA)

  8. VLDL hydrolysis by hepatic lipase regulates PPARδ transcriptional responses.

    Directory of Open Access Journals (Sweden)

    Jonathan D Brown

    Full Text Available PPARs (α,γ,δ are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL, an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown.Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP, angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro.These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid

  9. Dynamic regulation of hepatic lipid droplet properties by diet.

    Science.gov (United States)

    Crunk, Amanda E; Monks, Jenifer; Murakami, Aya; Jackman, Matthew; Maclean, Paul S; Ladinsky, Mark; Bales, Elise S; Cain, Shannon; Orlicky, David J; McManaman, James L

    2013-01-01

    Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low- and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.

  10. Regulating deregulated energy markets

    International Nuclear Information System (INIS)

    Jackson, M.

    2002-01-01

    The North American gas and electricity markets are fast evolving, and regulators are currently faced with a host of issues such as market-based rates, unbundling, stranded costs, open access, and incentive regulation are surfacing as a result of deregulation. The regulatory environment in Ontario was reviewed by the author. Deregulated markets rule, from commodities to gas and electricity. Additionally, there is an evolution of traditional utility regulation. A look at deregulated markets revealed that there are regulations on boundary conditions on the deregulated market. Under the Ontario Energy Board (OEB), all generators, transmitters, distributors, and retailers of electricity must be licensed. The standard supply service (SSS) offered by electricity distributors and system gas which is still being sold by natural gas distributors continues to be regulated by OEB. One issue that was addressed was separation for revenues and costs of the utility's purchase and sale of gas business, at least for accounting purposes. The next issue discussed was cost of system gas and SSS, followed by timely signals and prudent incurred costs. Historical benefits were reviewed, such as historical commitments to low-cost electricity. Pooling transportation costs, transmission pricing continued, market-based rates, unbundling, stranded costs, open access, incentive regulation/ performance based regulation (PBR) were all discussed. Price cap on PBR, both partial and comprehensive were looked at. A requirement to review guidelines on cost of capital and an application to extend blanket approval provisions for gas storage were discussed, as they are amongst some of the challenges of the future. Other challenges include revised rules and practice and procedure; practice directions for cost awards, appeals, and other functions; confidentiality guidelines; and refinements to the role of and approaches to alternative dispute resolution. The future role of regulators was examined in light

  11. CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism.

    Science.gov (United States)

    Peterson, Jonathan M; Seldin, Marcus M; Wei, Zhikui; Aja, Susan; Wong, G William

    2013-08-01

    CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and is downregulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established. Here, we used a transgenic mouse model to address the potential function of CTRP3 in ameliorating high-fat diet-induced metabolic stress. Both transgenic and wild-type mice fed a high-fat diet showed similar body weight gain, food intake, and energy expenditure. Despite similar adiposity to wild-type mice upon diet-induced obesity (DIO), CTRP3 transgenic mice were strikingly resistant to the development of hepatic steatosis, had reduced serum TNF-α levels, and demonstrated a modest improvement in systemic insulin sensitivity. Additionally, reduced hepatic triglyceride levels were due to decreased expression of enzymes (GPAT, AGPAT, and DGAT) involved in triglyceride synthesis. Importantly, short-term daily administration of recombinant CTRP3 to DIO mice for 5 days was sufficient to improve the fatty liver phenotype, evident as reduced hepatic triglyceride content and expression of triglyceride synthesis genes. Consistent with a direct effect on liver cells, recombinant CTRP3 treatment reduced fatty acid synthesis and neutral lipid accumulation in cultured rat H4IIE hepatocytes. Together, these results establish a novel role for CTRP3 hormone in regulating hepatic lipid metabolism and highlight its protective function and therapeutic potential in attenuating hepatic steatosis.

  12. NFIL3 is a negative regulator of hepatic gluconeogenesis.

    Science.gov (United States)

    Kang, Geon; Han, Hye-Sook; Koo, Seung-Hoi

    2017-12-01

    Nuclear factor interleukin-3 regulated (NFIL3) has been known as an important transcriptional regulator of the development and the differentiation of immune cells. Although expression of NFIL3 is regulated by nutritional cues in the liver, the role of NFIL3 in the glucose metabolism has not been extensively studied. Thus, we wanted to explore the potential role of NFIL3 in the control of hepatic glucose metabolism. Mouse primary hepatocytes were cultured to perform western blot analysis, Q-PCR and chromatin immunoprecipitation assay. 293T cells were cultured to perform luciferase assay. Male C57BL/6 mice (fed a normal chow diet or high fat diet for 27weeks) as well as ob/ob mice were used for experiments with adenoviral delivery. We observed that NFIL3 reduced glucose production in hepatocytes by reducing expression of gluconeogenic gene transcription. The repression by NFIL3 required its basic leucine zipper DNA binding domain, and it competed with CREB onto the binding of cAMP response element in the gluconeogenic promoters. The protein levels of hepatic NFIL3 were decreased in the mouse models of genetic- and diet-induced obesity and insulin resistance, and ectopic expression of NFIL3 in the livers of insulin resistant mice ameliorated hyperglycemia and glucose intolerance, with concomitant reduction in expression of hepatic gluconeogenic genes. Finally, we witnessed that knockdown of NFIL3 in the livers of normal chow-fed mice promoted elevations in the glucose levels and expression of hepatic gluconeogenic genes. In this study, we showed that NFIL3 functions as an important regulator of glucose homeostasis in the liver by limiting CREB-mediated hepatic gluconeogenesis. Thus, enhancement of hepatic NFIL3 activity in insulin resistant state could be potentially beneficial in relieving glycemic symptoms in the metabolic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. DMPD: Iron regulation of hepatic macrophage TNFalpha expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11841920 Iron regulation of hepatic macrophage TNFalpha expression. Tsukamoto H. Fr...ee Radic Biol Med. 2002 Feb 15;32(4):309-13. (.png) (.svg) (.html) (.csml) Show Iron regulation of hepatic macrophage... TNFalpha expression. PubmedID 11841920 Title Iron regulation of hepatic macrophage TNFalpha expres

  14. Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21.

    Science.gov (United States)

    Li, Yu; Wong, Kimberly; Giles, Amber; Jiang, Jianwei; Lee, Jong Woo; Adams, Andrew C; Kharitonenkov, Alexei; Yang, Qin; Gao, Bin; Guarente, Leonard; Zang, Mengwei

    2014-02-01

    The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased

  15. Autonomic regulation of hepatic glucose production

    NARCIS (Netherlands)

    Bisschop, Peter H.; Fliers, Eric; Kalsbeek, Andries

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system

  16. Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

    Directory of Open Access Journals (Sweden)

    Santiago Vernia

    2016-03-01

    Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

  17. Tribbles-1: a novel regulator of hepatic lipid metabolism in humans.

    Science.gov (United States)

    Bauer, Robert C; Yenilmez, Batuhan O; Rader, Daniel J

    2015-10-01

    The protein tribbles-1, encoded by the gene TRIB1, is increasingly recognized as a major regulator of multiple cellular and physiological processes in humans. Recent human genetic studies, as well as molecular biological approaches, have implicated this intriguing protein in the aetiology of multiple human diseases, including myeloid leukaemia, Crohn's disease, non-alcoholic fatty liver disease (NAFLD), dyslipidaemia and coronary artery disease (CAD). Genome-wide association studies (GWAS) have repeatedly identified variants at the genomic TRIB1 locus as being significantly associated with multiple plasma lipid traits and cardiovascular disease (CVD) in humans. The involvement of TRIB1 in hepatic lipid metabolism has been validated through viral-mediated hepatic overexpression of the gene in mice; increasing levels of TRIB1 decreased plasma lipids in a dose-dependent manner. Additional studies have implicated TRIB1 in the regulation of hepatic lipogenesis and NAFLD. The exact mechanisms of TRIB1 regulation of both plasma lipids and hepatic lipogenesis remain undetermined, although multiple signalling pathways and transcription factors have been implicated in tribbles-1 function. Recent reports have been aimed at developing TRIB1-based lipid therapeutics. In summary, tribbles-1 is an important modulator of human energy metabolism and metabolic syndromes and worthy of future studies aimed at investigating its potential as a therapeutic target. © 2015 Authors; published by Portland Press Limited.

  18. Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

    DEFF Research Database (Denmark)

    Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

    2016-01-01

    expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...... availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation....

  19. Hepatic p38α regulates gluconeogenesis by suppressing AMPK.

    Science.gov (United States)

    Jing, Yanyan; Liu, Wei; Cao, Hongchao; Zhang, Duo; Yao, Xuan; Zhang, Shengjie; Xia, Hongfeng; Li, Dan; Wang, Yu-cheng; Yan, Jun; Hui, Lijian; Ying, Hao

    2015-06-01

    It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38α in gluconeogenesis during fasting by applying a loss-of-function genetic approach. We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38α in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38α (p38α-AF) and the constitutively active mitogen-activated protein kinase 6, respectively. Adenoviral dominant-negative form of AMP-activated protein kinase α (DN-AMPKα) was employed to test our proposed model. Mice lacking hepatic p38α exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38α did not result in an alteration in CREB phosphorylation, but led to an increase in AMPKα phosphorylation. Adenoviral DN-AMPKα could abolish the effect of p38α-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor β-activated kinase 1 decreased the AMPKα phosphorylation induced by p38α-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKα phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38α-AF treatment ameliorated hyperglycemia in diabetic mice. Our study provides evidence that hepatic p38α functions as a negative regulator of AMPK signaling in maintaining gluconeogenesis, dysregulation of this regulatory network contributes to unrestrained gluconeogenesis in diabetes, and hepatic p38α could be a drug target for hyperglycemia. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

    Science.gov (United States)

    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

    2015-01-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

  1. PPARα is a key regulator of hepatic FGF21

    International Nuclear Information System (INIS)

    Lundasen, Thomas; Hunt, Mary C.; Nilsson, Lisa-Mari; Sanyal, Sabyasachi; Angelin, Bo; Alexson, Stefan E.H.; Rudling, Mats

    2007-01-01

    The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARα). Fasting or treatment of mice with the PPARα agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARα deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARα levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARα for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARα response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARα in humans will be of great interest

  2. The Histone Demethylase Jhdm1a Regulates Hepatic Gluconeogenesis

    Science.gov (United States)

    Zou, Tie; Yao, Annie Y.; Cooper, Marcus P.; Boyartchuk, Victor; Wang, Yong-Xu

    2012-01-01

    Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36) demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes. PMID:22719268

  3. The histone demethylase Jhdm1a regulates hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Dongning Pan

    Full Text Available Hepatic gluconeogenesis is required for maintaining blood glucose homeostasis; yet, in diabetes mellitus, this process is unrestrained and is a major contributor to fasting hyperglycemia. To date, the impacts of chromatin modifying enzymes and chromatin landscape on gluconeogenesis are poorly understood. Through catalyzing the removal of methyl groups from specific lysine residues in the histone tail, histone demethylases modulate chromatin structure and, hence, gene expression. Here we perform an RNA interference screen against the known histone demethylases and identify a histone H3 lysine 36 (H3K36 demethylase, Jhdm1a, as a key negative regulator of gluconeogenic gene expression. In vivo, silencing of Jhdm1a promotes liver glucose synthesis, while its exogenous expression reduces blood glucose level. Importantly, the regulation of gluconeogenesis by Jhdm1a requires its demethylation activity. Mechanistically, we find that Jhdm1a regulates the expression of a major gluconeogenic regulator, C/EBPα. This is achieved, at least in part, by its USF1-dependent association with the C/EBPα promoter and its subsequent demethylation of dimethylated H3K36 on the C/EBPα locus. Our work provides compelling evidence that links histone demethylation to transcriptional regulation of gluconeogenesis and has important implications for the treatment of diabetes.

  4. Hepatitis

    Science.gov (United States)

    ... most common types of viral hepatitis. What Is Hepatitis A? For kids, hep A is the most common ... they recover, it does not come back. Can Hepatitis A Be Prevented? The following will help keep people ...

  5. Regulation of hepatic PPARγ2 and lipogenic gene expression by melanocortin

    International Nuclear Information System (INIS)

    Poritsanos, Nicole J.; Wong, Davie; Vrontakis, Maria E.; Mizuno, Tooru M.

    2008-01-01

    The central melanocortin system regulates hepatic lipid metabolism. Hepatic lipogenic gene expression is regulated by transcription factors including sterol regulatory element-binding protein 1c (SREBP-1c), carbohydrate responsive element-binding protein (ChREBP), and peroxisome proliferator-activated receptor γ2 (PPARγ2). However, it is unclear if central melanocortin signaling regulates hepatic lipogenic gene expression through the activation of these transcription factors. To delineate the molecular mechanisms by which the melanocortin system regulates hepatic lipid metabolism, we examined the effect of intracerebroventricular injection of SHU9119, a melanocortin receptor antagonist, on hepatic expression levels of genes involved in lipid metabolism in mice. SHU9119 treatment increased hepatic triglyceride content and mRNA levels of lipogenic genes, SREBP-1c, and PPARγ2, whereas it did not cause any changes in hepatic ChREBP mRNA levels. These findings suggest that reduced central melanocortin signaling increases hepatic lipid deposition by stimulating hepatic lipogenic gene expression at least partly through the activation of SREBP-1c and PPARγ2

  6. SREBP-1c regulates glucose-stimulated hepatic clusterin expression

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gukhan [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Geun Hyang; Oh, Gyun-Sik; Yoon, Jin [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Hae Won [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Min-Seon [Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Seung-Whan, E-mail: swkim7@amc.seoul.kr [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2011-05-20

    Highlights: {yields} This is the first report to show nutrient-regulated clusterin expression. {yields} Clusterin expression in hepatocytes was increased by high glucose concentration. {yields} SREBP-1c is directly involved in the transcriptional activation of clusterin by glucose. {yields} This glucose-stimulated activation process is mediated through tandem E-box motifs. -- Abstract: Clusterin is a stress-response protein that is involved in diverse biological processes, including cell proliferation, apoptosis, tissue differentiation, inflammation, and lipid transport. Its expression is upregulated in a broad spectrum of diverse pathological states. Clusterin was recently reported to be associated with diabetes, metabolic syndrome, and their sequelae. However, the regulation of clusterin expression by metabolic signals was not addressed. In this study we evaluated the effects of glucose on hepatic clusterin expression. Interestingly, high glucose concentrations significantly increased clusterin expression in primary hepatocytes and hepatoma cell lines, but the conventional promoter region of the clusterin gene did not respond to glucose stimulation. In contrast, the first intronic region was transcriptionally activated by high glucose concentrations. We then defined a glucose response element (GlRE) of the clusterin gene, showing that it consists of two E-box motifs separated by five nucleotides and resembles carbohydrate response element (ChoRE). Unexpectedly, however, these E-box motifs were not activated by ChoRE binding protein (ChREBP), but were activated by sterol regulatory element binding protein-1c (SREBP-1c). Furthermore, we found that glucose induced recruitment of SREBP-1c to the E-box of the clusterin gene intronic region. Taken together, these results suggest that clusterin expression is increased by glucose stimulation, and SREBP-1c plays a crucial role in the metabolic regulation of clusterin.

  7. Estrogens regulate the hepatic effects of growth hormone, a hormonal interplay with multiple fates

    DEFF Research Database (Denmark)

    Fernández-Pérez, Leandro; Guerra, Borja; Díaz-Chico, Juan C

    2013-01-01

    The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk...

  8. Ubiquitin-Specific Protease 2 Regulates Hepatic Gluconeogenesis and Diurnal Glucose Metabolism Through 11β-Hydroxysteroid Dehydrogenase 1

    Science.gov (United States)

    Molusky, Matthew M.; Li, Siming; Ma, Di; Yu, Lei; Lin, Jiandie D.

    2012-01-01

    Hepatic gluconeogenesis is important for maintaining steady blood glucose levels during starvation and through light/dark cycles. The regulatory network that transduces hormonal and circadian signals serves to integrate these physiological cues and adjust glucose synthesis and secretion by the liver. In this study, we identified ubiquitin-specific protease 2 (USP2) as an inducible regulator of hepatic gluconeogenesis that responds to nutritional status and clock. Adenoviral-mediated expression of USP2 in the liver promotes hepatic glucose production and exacerbates glucose intolerance in diet-induced obese mice. In contrast, in vivo RNA interference (RNAi) knockdown of this factor improves systemic glycemic control. USP2 is a target gene of peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α), a coactivator that integrates clock and energy metabolism, and is required for maintaining diurnal glucose homeostasis during restricted feeding. At the mechanistic level, USP2 regulates hepatic glucose metabolism through its induction of 11β-hydroxysteroid dehydrogenase 1 (HSD1) and glucocorticoid signaling in the liver. Pharmacological inhibition and liver-specific RNAi knockdown of HSD1 significantly impair the stimulation of hepatic gluconeogenesis by USP2. Together, these studies delineate a novel pathway that links hormonal and circadian signals to gluconeogenesis and glucose homeostasis. PMID:22447855

  9. Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Minqian Shen

    2015-01-01

    Full Text Available The liver is one of the most essential organs involved in the regulation of energy homeostasis. Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis. In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver. In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism. In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver. These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis.

  10. The Regulation of Energy Medicine

    Science.gov (United States)

    Kosovich, Judy; Esq

    This paper describes the laws and regulations that affect the practice of energy medicine. State law often has more impact on a health care practice than federal law, but federal law provides a common denominator among states. Device law is emphasized here because practitioners of energy medicine are more likely to use devices than drugs. For purposes of this paper, energy medicine is defined as practices that measure or benefit energy flow and overall energy in the body. This broad definition encompasses things as diverse as certain forms of exercise, measurement of meridian resistance, the use of electrical current or magnetic pulses to relieve pain, and the use of light, sound, scent, touch, position, or movement to stimulate the body's own electrical systems. What is of greatest importance in determining legal implications of a practice is whether there are any health-related claims. Two federal entities are pivotal. The Food and Drug Administration ("FDA") is authorized to protect health and safety and the Federal Trade Commission ("FTC") is authorized to protect consumers from false or misleading advertising. There are 5 things that FDA looks at: 1) intended use, 2) claims made in advertising and in labeling, 3) substantial equivalence to a predicate, 4) safety, and 5) effectiveness. A concern regarding any one of these can be the basis for denying clearance to market a device. The FTC looks at whether statements are true and substantiated and whether they might be misleading. The FTC often consults with the FDA on the interpretation of technical information.

  11. Hepatic CREB3L3 controls whole-body energy homeostasis and improves obesity and diabetes.

    Science.gov (United States)

    Nakagawa, Yoshimi; Satoh, Aoi; Yabe, Sachiko; Furusawa, Mika; Tokushige, Naoko; Tezuka, Hitomi; Mikami, Motoki; Iwata, Wakiko; Shingyouchi, Akiko; Matsuzaka, Takashi; Kiwata, Shiori; Fujimoto, Yuri; Shimizu, Hidehisa; Danno, Hirosuke; Yamamoto, Takashi; Ishii, Kiyoaki; Karasawa, Tadayoshi; Takeuchi, Yoshinori; Iwasaki, Hitoshi; Shimada, Masako; Kawakami, Yasushi; Urayama, Osamu; Sone, Hirohito; Takekoshi, Kazuhiro; Kobayashi, Kazuto; Yatoh, Shigeru; Takahashi, Akimitsu; Yahagi, Naoya; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

    2014-12-01

    Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

  12. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

    Science.gov (United States)

    Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

    2016-06-01

    Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis.

    Science.gov (United States)

    Kim, Hyunbae; Zheng, Ze; Walker, Paul D; Kapatos, Gregory; Zhang, Kezhong

    2017-07-15

    Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress. Copyright © 2017 American Society for Microbiology.

  14. The effect of energy performance regulations on energy consumption

    NARCIS (Netherlands)

    Guerra-Santin, O.; Itard, L.

    2012-01-01

    Governments have developed energy performance regulations in order to lower energy consumption in the housing stock. Most of these regulations are based on the thermal quality of the buildings. In the Netherlands, the energy efficiency for new buildings is expressed as the EPC (energy performance

  15. A better regulation is required in viral hepatitis smartphone applications

    Directory of Open Access Journals (Sweden)

    M.ª R. Cantudo-Cuenca

    2014-03-01

    Full Text Available Aim. To describe the characteristics and content of the available viral hepatitis mobile applications, as well as assess the level of participation of medical professionals in their development. Methods. A descriptive observational study was carried out in September 2013. We searched smartphone apps specifically relating to the viral hepatitis for using a keyword search with the following terms; «hepatitis», «hepatology», «hbv» and «hcv» in the Google Play Store (Android and the Apple App Store (iOS. Data recorded included: name, platform, category, cost, user star rating, number of downloads, date the app was updated by the developer and target audience. We analysed the content of the applications, and these were then categorised based on the viral hepatitis type into three groups. We conducted an analysis in which we specifically examined the authorship in order to assess the prevalence of health professional participation in their development. Results. A total of 33 apps were included (from 232 that were identified, among which there were 10 duplicates. Most of these apps were uploaded under the medical category. Three had ratings less than 3.9 stars (out of 5. Only 6 apps had exceeded 1000 downloads. A total of 12 apps were aimed at health professionals, while 4 focused on patients (7 for both of them. The participation of health professionals in the development of apps was 56.6%. Conclusions. Viral hepatitis apps are available for both professionals and patients; however, much of the information contained within them is often not validated. They should be certificated.

  16. A better regulation is required in viral hepatitis smartphone applications.

    Science.gov (United States)

    Cantudo-Cuenca, Ma R; Robustillo-Cortés, Ma A; Cantudo-Cuenca, Ma D; Morillo-Verdugo, R

    2014-04-01

    To describe the characteristics and content of the available viral hepatitis mobile applications, as well as assess the level of participation of medical professionals in their development. A descriptive observational study was carried out in September 2013. We searched smartphone apps specifically relating to the viral hepatitis for using a keyword search with the following terms; «hepatitis», «hepatology», «hbv» and «hcv» in the Google Play Store (Android) and the Apple App Store (iOS). Data recorded included: name, platform, category, cost, user star rating, number of downloads, date the app was updated by the developer and target audience. We analysed the content of the applications, and these were then categorised based on the viral hepatitis type into three groups. We conducted an analysis in which we specifically examined the authorship in order to assess the prevalence of health professional participation in their development. A total of 33 apps were included (from 232 that were identified), among which there were 10 duplicates. Most of these apps were uploaded under the medical category. Three had ratings less than 3.9 stars (out of 5). Only 6 apps had exceeded 1000 downloads. A total of 12 apps were aimed at health professionals, while 4 focused on patients (7 for both of them). The participation of health professionals in the development of apps was 56.6%. Viral hepatitis apps are available for both professionals and patients; however, much of the information contained within them is often not validated. They should be certificated. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  17. Constructing regulation and regulating for energy efficient construction

    Energy Technology Data Exchange (ETDEWEB)

    Shove, Elizabeth [Lancaster University (United Kingdom). Centre for the Study of Environmental Change

    1998-07-01

    This project considers the process of formulating energy-related building regulation in the light of the revisions to Part L (Conservation of Fuel and Power) of the Building Regulations for England and Wales. Details are given of the main objectives of the research, namely, the examination of the roles of the UK government, local government and pressure groups in shaping energy efficiency standards, the impacts of environmental regulations, the limits of energy-related regulation, environmental regulation of the building sector, and the features of energy related building control. This control is compared with current practice in other European countries. The methodology of the project involving the review of governmental documents and interviews is described. (UK)

  18. Pollution Under Environmental Regulation in Energy Markets

    CERN Document Server

    Gullì, Francesco

    2013-01-01

    Pollution Under Environmental Regulation in Energy Markets provides a study of environmental regulation when energy markets are imperfectly competitive. This theoretical treatment focuses on three relevant cases of energy markets. First, the residential space heating sector where hybrid regulation such as taxation and emissions trading together are possible. Second, the electricity market where transactions are organized in the form of multi-period auctions. Third, namely natural gas (input) and electricity (output) markets where there is combined imperfect competition in vertical related energy markets.   The development of free or low carbon technologies supported by energy policies, aiming at increasing security of supply, is also explored whilst considering competition policies that reduce market power in energy markets thus improving market efficiency. Pollution Under Environmental Regulation in Energy Markets discusses the key issues of whether imperfect competition can lessen the ability of environmen...

  19. Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing.

    Directory of Open Access Journals (Sweden)

    Helen J Renaud

    Full Text Available The liver plays a central role in metabolic homeostasis by coordinating synthesis, storage, breakdown, and redistribution of nutrients. Hepatic energy metabolism is dynamically regulated throughout different life stages due to different demands for energy during growth and development. However, changes in gene expression patterns throughout ontogeny for factors important in hepatic energy metabolism are not well understood. We performed detailed transcript analysis of energy metabolism genes during various stages of liver development in mice. Livers from male C57BL/6J mice were collected at twelve ages, including perinatal and postnatal time points (n = 3/age. The mRNA was quantified by RNA-Sequencing, with transcript abundance estimated by Cufflinks. One thousand sixty energy metabolism genes were examined; 794 were above detection, of which 627 were significantly changed during at least one developmental age compared to adult liver. Two-way hierarchical clustering revealed three major clusters dependent on age: GD17.5-Day 5 (perinatal-enriched, Day 10-Day 20 (pre-weaning-enriched, and Day 25-Day 60 (adolescence/adulthood-enriched. Clustering analysis of cumulative mRNA expression values for individual pathways of energy metabolism revealed three patterns of enrichment: glycolysis, ketogenesis, and glycogenesis were all perinatally-enriched; glycogenolysis was the only pathway enriched during pre-weaning ages; whereas lipid droplet metabolism, cholesterol and bile acid metabolism, gluconeogenesis, and lipid metabolism were all enriched in adolescence/adulthood. This study reveals novel findings such as the divergent expression of the fatty acid β-oxidation enzymes Acyl-CoA oxidase 1 and Carnitine palmitoyltransferase 1a, indicating a switch from mitochondrial to peroxisomal β-oxidation after weaning; as well as the dynamic ontogeny of genes implicated in obesity such as Stearoyl-CoA desaturase 1 and Elongation of very long chain fatty

  20. Immune regulation in chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou

    2016-01-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion...... and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs...

  1. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation

    Science.gov (United States)

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFkβ pathway (IκBα) by TNF-α was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-α blockage by anti-TNF-α in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-α). PMID:25197426

  2. Regulation - renewable energies finally liberated?

    International Nuclear Information System (INIS)

    Blosseville, Thomas

    2016-01-01

    Within the context defined by the new French policy for energy transition, notably in terms of share of renewable energies in final energy consumption, France seems to be somehow late in the development of these energies: about 1 GW of wind energy are installed each year when the expected pace would be 1,5 GW, and the photovoltaic market is shrinking. As the legal context is important, this article proposes an overview of the evolution of the French policy during the last four years which started with interesting measures. Recently, the government showed its will to liberate renewable energies from several constraints. Some legal procedures tend to slow down the development. Some advances could therefore be made, for example to make rules less complex and numerous. The different situations of the wind and biogas sectors are evoked, as well as new opportunities created by a new decree on investment planning

  3. Interlaced Energy Linac with Smooth Energy Regulation

    CERN Document Server

    Wronka, Sławomir

    2016-01-01

    2 A bstract Radiation is commonly used in many branches of every d ay life. Applications of ionization radiation sources in wide range of energy as well as precise detectors cover a number of areas, from basic research, medical treatment, industrial processing, environmental protection, non - destructive testing to safety a nd security. Accelerator and X - ray tube based techniques are increasingly used in luggage and cargo inspection, smuggling detection of explosives and of nuclear materials. The development of new technologies and new features of “classical” machines can be observed recently with the same, well known physics inside. This report is intended to provide the readers with newly developed at NCBJ experimental stand for cargo screening tests, equipped with linear interlaced - energy accelerator.

  4. Comprehensive analysis of PPARα-dependent regulation of hepatic lipid metabolism by expression profiling - 5

    NARCIS (Netherlands)

    Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

    2007-01-01

    PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an

  5. Comprehensive analysis of PPARa-dependent regulation of hepatic lipid metabolism by expression profiling

    NARCIS (Netherlands)

    Rakhshandehroo, Maryam; Sanderson-Kjellberg, L.M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; Groot, de Philip; Muller, Michael; Kersten, Sander

    2007-01-01

    PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to

  6. Postprandial regulation of hepatic microRNAs predicted to target the insulin pathway in rainbow trout.

    Directory of Open Access Journals (Sweden)

    Jan A Mennigen

    Full Text Available Rainbow trout are carnivorous fish and poor metabolizers of carbohydrates, which established this species as a model organism to study the comparative physiology of insulin. Following the recent characterisation of key roles of several miRNAs in the insulin action on hepatic intermediary metabolism in mammalian models, we investigated the hypothesis that hepatic miRNA expression is postprandially regulated in the rainbow trout and temporally coordinated in the context of insulin-mediated regulation of metabolic gene expression in the liver. To address this hypothesis, we used a time-course experiment in which rainbow trout were fed a commercial diet after short-term fasting. We investigated hepatic miRNA expression, activation of the insulin pathway, and insulin regulated metabolic target genes at several time points. Several miRNAs which negatively regulate hepatic insulin signaling in mammalian model organisms were transiently increased 4 h after the meal, consistent with a potential role in acute postprandial negative feed-back regulation of the insulin pathway and attenuation of gluconeogenic gene expression. We equally observed a transient increase in omy- miRNA-33 and omy-miRNA-122b 4 h after feeding, whose homologues have potent lipogenic roles in the liver of mammalian model systems. A concurrent increase in the activity of the hepatic insulin signaling pathway and the expression of lipogenic genes (srebp1c, fas, acly was equally observed, while lipolytic gene expression (cpt1a and cpt1b decreased significantly 4 h after the meal. This suggests lipogenic roles of omy-miRNA-33 and omy-miRNA-122b may be conserved between rainbow trout and mammals and that these miRNAs may furthermore contribute to acute postprandial regulation of de novo hepatic lipid synthesis in rainbow trout. These findings provide a framework for future research of miRNA regulation of hepatic metabolism in trout and will help to further elucidate the metabolic

  7. The need for regulation in energy markets

    International Nuclear Information System (INIS)

    De Sampaio Nunes, P.

    2002-01-01

    The following topics are discussed: The need for effective regulation; Energy issues requiring regulatory policy; Models adopted in different Member States of the European Union; Results achieved by Member States; Infrastructure. (R.P.)

  8. Research advances in microRNAs in regulating hepatitis C virus replication and antiviral therapy

    Directory of Open Access Journals (Sweden)

    CUI Xianghua

    2015-05-01

    Full Text Available Hepatitis C virus (HCV infection is one of the most common causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. MicroRNAs (miRNAs, a class of small, non-coding RNA, are involved in a variety of physiological and pathological processes in human bodies. The mechanism by which miRNAs regulate HCV replication is described, and the effects of liver-specific microRNA-122 antagonists on hepatitis C antiviral therapy are discussed. Our study indicates that miRNAs play an important regulatory role in HCV expression. Targeting miRNAs may be a potential therapeutic approach for treating HCV infection, but further studies are still in need.

  9. Regulation of hepatic lipase activity by sphingomyelin in plasma lipoproteins.

    Science.gov (United States)

    Yang, Peng; Subbaiah, Papasani V

    2015-10-01

    Hepatic lipase (HL) is an important enzyme in the clearance of triacylglycerol (TAG) from the circulation, and has been proposed to have pro-atherogenic as well as anti-atherogenic properties. It hydrolyzes both phospholipids and TAG of lipoproteins, and its activity is negatively correlated with HDL levels. Although it is known that HL acts preferentially on HDL lipids, the basis for this specificity is not known, since it does not require any specific apoprotein for activity. In this study, we tested the hypothesis that sphingomyelin (SM), whose concentration is much higher in VLDL and LDL compared to HDL, is an inhibitor of HL, and that this could explain the lipoprotein specificity of the enzyme. The results presented show that the depletion of SM from normal lipoproteins activated the HL roughly in proportion to their SM content. SM depletion stimulated the hydrolysis of both phosphatidylcholine (PC) and TAG, although the PC hydrolysis was stimulated more. In the native lipoproteins, HL showed specificity for PC species containing polyunsaturated fatty acids at sn-2 position, and produced more unsaturated lyso PC species. The enzyme also showed preferential hydrolysis of certain TAG species over others. SM depletion affected the specificity of the enzyme towards PC and TAG species modestly. These results show that SM is a physiological inhibitor of HL activity in lipoproteins and that the specificity of the enzyme towards HDL is at least partly due to its low SM content. Published by Elsevier B.V.

  10. Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

    Science.gov (United States)

    Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

    2018-01-01

    Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

  11. Commission of energy regulation. 2004 activity report

    International Nuclear Information System (INIS)

    2004-01-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  12. Regulation of Hepatic Stellate Cells and Fibrogenesis by Fibroblast Growth Factors

    Directory of Open Access Journals (Sweden)

    Justin D. Schumacher

    2016-01-01

    Full Text Available Fibroblast growth factors (FGFs are a family of growth factors critically involved in developmental, physiological, and pathological processes, including embryogenesis, angiogenesis, wound healing, and endocrine functions. In the liver, several FGFs are produced basally by hepatocytes and hepatic stellate cells (HSCs. Upon insult to the liver, expression of FGFs in HSCs is greatly upregulated, stimulating hepatocyte regeneration and growth. Various FGF isoforms have also been shown to directly induce HSC proliferation and activation thereby enabling autocrine and paracrine regulation of HSC function. Regulation of HSCs by the endocrine FGFs, namely, FGF15/19 and FGF21, has also recently been identified. With the ability to modulate HSC proliferation and transdifferentiation, targeting FGF signaling pathways constitutes a promising new therapeutic strategy to treat hepatic fibrosis.

  13. DMT efficiently inhibits hepatic gluconeogenesis by regulating the Gαq signaling pathway.

    Science.gov (United States)

    Zhou, Ting-Ting; Ma, Fei; Shi, Xiao-Fan; Xu, Xin; Du, Te; Guo, Xiao-Dan; Wang, Gai-Hong; Yu, Liang; Rukachaisirikul, Vatcharin; Hu, Li-Hong; Chen, Jing; Shen, Xu

    2017-08-01

    Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with complicated pathogenesis and targeting gluconeogenesis inhibition is a promising strategy for anti-diabetic drug discovery. G protein-coupled receptors (GPCRs) are classified as distinct families by heterotrimeric G proteins, primarily including Gαs, Gαi and Gαq. Gαs-coupled GPCRs function potently in the regulation of hepatic gluconeogenesis by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway and Gαi-coupled GPCRs exhibit inhibitory effect on adenylyl cyclase and reduce intracellular cAMP level. However, little is known about the regulation of Gαq-coupled GPCRs in hepatic gluconeogenesis. Here, small-molecule 2-(2,4-dimethoxy-3-methylphenyl)-7-(thiophen-2-yl)-9-(trifluoromethyl)-2,3-dihydropyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4( 1H )-one (DMT) was determined to suppress hepatic glucose production and reduce mRNA levels of gluconeogenic genes. Treatment of DMT in db/db mice decreased fasting blood glucose and hemoglobin A1C (HbA1c) levels, while improved glucose tolerance and pyruvate tolerance. Mechanism study demonstrated that DMT-inhibited gluconeogenesis by regulating the Gαq/phospholipase C (PLC)/inositol-1,4,5-triphosphate receptor (IP3R)-mediated calcium (Ca 2+ )/calmodulin (CaM)/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/forkhead box protein O1 (FOXO1) signaling pathway. To our knowledge, DMT might be the first reported small molecule able to suppress hepatic gluconeogenesis by regulating Gαq signaling, and our current work has also highlighted the potential of DMT in the treatment of T2DM. © 2017 Society for Endocrinology.

  14. Estrogens regulate the hepatic effects of Growth Hormone, a hormonal interplay with multiple fates

    Directory of Open Access Journals (Sweden)

    Leandro eFernandez-Perez

    2013-06-01

    Full Text Available The liver responds to estrogens and GH which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This cross-talk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency.

  15. CREB and FoxO1: two transcription factors for the regulation of hepatic gluconeogenesis

    Science.gov (United States)

    Oh, Kyoung-Jin; Han, Hye-Sook; Kim, Min-Jung; Koo, Seung-Hoi

    2013-01-01

    Liver plays a major role in maintaining glucose homeostasis in mammals. Under fasting conditions, hepatic glucose production is critical as a source of fuel to maintain the basic functions in other tissues, including skeletal muscle, red blood cells, and the brain. Fasting hormones glucagon and cortisol play major roles during the process, in part by activating the transcription of key enzyme genes in the gluconeogenesis such as phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6 phosphatase catalytic subunit (G6Pase). Conversely, gluconeogenic transcription is repressed by pancreatic insulin under feeding conditions, which effectively inhibits transcriptional activator complexes by either promoting post-translational modifications or activating transcriptional inhibitors in the liver, resulting in the reduction of hepatic glucose output. The transcriptional regulatory machineries have been highlighted as targets for type 2 diabetes drugs to control glycemia, so understanding of the complex regulatory mechanisms for transcription circuits for hepatic gluconeogenesis is critical in the potential development of therapeutic tools for the treatment of this disease. In this review, the current understanding regarding the roles of two key transcriptional activators, CREB and FoxO1, in the regulation of hepatic gluconeogenic program is discussed. [BMB Reports 2013; 46(12): 567-574] PMID:24238363

  16. Tariff regulation with energy efficiency goals

    International Nuclear Information System (INIS)

    Abrardi, Laura; Cambini, Carlo

    2015-01-01

    We study the optimal tariff structure that could induce a regulated utility to promote energy efficiency by its customers given that it is privately informed about the effectiveness of its effort on demand reduction. The regulator should optimally offer a menu of incentive compatible two-part tariffs. If the firm's energy efficiency activities have a high impact on demand reduction, the consumer should pay a high fixed fee but a low per unit price, approximating the tariff structure to a decoupling policy, which strengthens the firm's incentives to pursue energy conservation. Instead, if the firm's effort to adopt energy efficiency actions is scarcely effective, the tariff is characterized by a low fixed fee but a high price per unit of energy consumed, thus shifting the incentives for energy conservation on consumers. The optimal tariff structure also depends on the cost of the consumer's effort (in case the consumer can also adopt energy efficiency measures) and on the degree of substitutability between the consumer's and the firm's efforts. - Highlights: • We study the optimal tariff structure that induces an utility to adopt energy efficiency activities. • The regulator optimally offer a menu of incentive compatible two-part tariffs. • If energy efficiency activities have a high effectiveness, decoupling emerges as a solution. • If the energy efficiency actions are less effective, the tariff has a higher per unit price and lower fixed fee. • The optimal tariff structure also depends on the degree of substitutability between the consumer's and the firm's efforts

  17. The g0/g1 switch gene 2 is an important regulator of hepatic triglyceride metabolism.

    Science.gov (United States)

    Wang, Yinfang; Zhang, Yahui; Qian, Hang; Lu, Juan; Zhang, Zhifeng; Min, Xinwen; Lang, Mingjian; Yang, Handong; Wang, Nanping; Zhang, Peng

    2013-01-01

    Nonalcoholic fatty liver disease is associated with obesity and insulin resistance. Factors that regulate the disposal of hepatic triglycerides contribute to the development of hepatic steatosis. G0/G1 switch gene 2 (G0S2) is a target of peroxisome proliferator-activated receptors and plays an important role in regulating lipolysis in adipocytes. Therefore, we investigated whether G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of G0S2 (Ad-G0S2) potently induced fatty liver in mice. The liver mass of Ad-G0S2-infected mice was markedly increased with excess triglyceride content compared to the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes. G0S2 was found to be co-localized with adipose triglyceride lipase at the surface of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma Low-density lipoprotein (LDL)/Very-Low-density (VLDL) lipoprotein cholesterol level. Plasma High-density lipoprotein (HDL) cholesterol and ketone body levels were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2 overexpression in the liver significantly improved glucose tolerance in mice. Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4-yl) amino)-6-deoxyglucose uptake compared with livers transfected with control adenovirus. Taken together, our results provide evidence supporting an important role for G0S2 as a regulator of triglyceride content in the liver and suggest that G0S2 may be a molecular target for the treatment of insulin resistance and other obesity-related metabolic disorders.

  18. Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio

    International Nuclear Information System (INIS)

    Janssens, P.A.; Lowrey, P.

    1987-01-01

    Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC 50 s of 100, 100, and 500 nM, respectively. These actions were blocked by the β-adrenergic antagonist, propranolol, but not by the α-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10 -6 M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10 -5 M isotocin and slightly decreased by 10 -6 M angiotensin II. [ 125 I]-iodocyanopindolol (ICP), a β-adrenergic ligand, bound to isolated carp liver membranes with a K/sub D/ of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with K/sub D/s of 100 nM, 2, 20, 20, 60, and 200 μM, respectively. The α-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via β-adrenergic receptors in carp liver and that α-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis

  19. Hepatic and cerebral energy metabolism after neonatal canine alimentation.

    Science.gov (United States)

    Kliegman, R M; Miettinen, E L; Morton, S K

    1983-04-01

    Intrahepatic and intracerebral metabolic responses to neonatal fasting or enteric carbohydrate alimentation were investigated among newborn dogs. Pups were either fasted or given an intravenous glucose infusion (alimented) before an enteric feeding of physiologic quantities of either glucose or galactose. These pups were also compared to another group which was completely starved throughout the study period. Gastrointestinal carbohydrate feeding resulted in enhanced hepatic glycogen content among pups after a prior state of fasting. Though there were no differences of glycogen content between glucose or galactose feeding in this previously fasted group, combined intravenous glucose and enteric galactose administration produced the greatest effect on hepatic glycogen synthesis. Intrahepatic fructose 1, 6-diphosphate and phosphoenolpyruvate levels were increased among previously fasted pups fed enteric monosaccharides compared to completely starved control pups, whereas intrahepatic phosphoenolpyruvate and pyruvate levels were elevated after combined intravenous and enteric carbohydrate administration. Of greater interest was the observation that hepatic levels of ATP were significantly elevated among all groups given exogenous carbohydrates compared to the completely starved control group. In contrast to the augmented hepatic glycogen and ATP levels, there were no alterations of cerebral glycogen or ATP after alimentation. Nevertheless, cerebral pyruvate and/or phosphoenolpyruvate concentrations were elevated after enteric or combined intravenous and enteric alimentation compared to the totally starved control pups.

  20. Municipalities as facilitators, regulators and energy consumers

    DEFF Research Database (Denmark)

    Lybæk, Rikke; Kjær, Tyge

    2015-01-01

    Biogas provides many potential benefits as far as renewable energy production, environmental protection and job creation etc. Insufficient initiatives from government/municipalities however hamper more biogas plants to be established, and hence that the large manure potential, and other types...... of digestible organic waste materials, are being utilized for energy purposes. By looking at municipalities as energy consumer’s, that constitutes a local market for biogas, as regulator’s, enforcing new requirements and regulations on the biogas sector, and finally as facilitator’s, assisting and helping...

  1. Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Lena Seifert

    2015-12-01

    Full Text Available Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1–/– mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

  2. Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways.

    Science.gov (United States)

    Seifert, Lena; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Werba, Gregor; Pansari, Mridul; Pergamo, Matthew; Ochi, Atsuo; Torres-Hernandez, Alejandro; Levie, Elliot; Tippens, Daniel; Greco, Stephanie H; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Eisenthal, Andrew; van Heerden, Eliza; Avanzi, Antonina; Barilla, Rocky; Zambirinis, Constantinos P; Rendon, Mauricio; Daley, Donnele; Pachter, H Leon; Hajdu, Cristina; Miller, George

    2015-12-01

    Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Commission for energy regulation - 2012 Activity Report

    International Nuclear Information System (INIS)

    2013-06-01

    After a presentation of the organisation, role and missions of the French Commission for Energy Regulation (CRE), and of its relationship with other institutional actors, this report describes and comments the action of the CRE in the fields of dialogue and transparency. It presents and comments key figures regarding the electricity and gas retail markets. It reports and comments the European reaction to the cold peak of February 2012 (historical peak for consumption and prices, inquiry on the causes of these price peaks, need of a European market). The next part addresses the relationship between electricity grids and territories (solidarity between electricity grids as the basis of the Europe of energy, evolution of French grids to face new needs and to take regional and local dimensions into account). Another part addresses gas infrastructures which are considered as the cornerstone of a good operation for the French market and for the integration of the European energy market (gas world market in 2012, definition of a target model for the gas market by European regulators, evolution of the French market in compliance with the European target model, new tariffs for the use of natural gas transport networks). The report then addresses the development of renewable energies: actions of CRE (bidding, opinion of tariffs), influence of renewable energy development on electricity prices on gross markets, needed evolution of electricity grids. A last part addresses the issues of energy cost, demand management, and struggle against energy poverty

  4. PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans

    DEFF Research Database (Denmark)

    Bezy, Olivier; Tran, Thien T; Pihlajamäki, Jussi

    2011-01-01

    C57BL/6J and 129S6/Sv (B6 and 129) mice differ dramatically in their susceptibility to developing diabetes in response to diet- or genetically induced insulin resistance. A major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding...... tolerance, and reduced hepatosteatosis with aging. Conversely, mice with liver-specific overexpression of PKCδ developed hepatic insulin resistance characterized by decreased insulin signaling, enhanced lipogenic gene expression, and hepatosteatosis. Therefore, changes in the expression and regulation...... of PKCδ between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance, glucose intolerance, and hepatosteatosis; and thus PKCδ may be a potential target in the treatment of metabolic syndrome....

  5. Biochanin A improves hepatic steatosis and insulin resistance by regulating the hepatic lipid and glucose metabolic pathways in diet-induced obese mice.

    Science.gov (United States)

    Park, Hee-Sook; Hur, Haeng Jeon; Kim, Soon-Hee; Park, Su-Jin; Hong, Moon Ju; Sung, Mi Jeong; Kwon, Dae Young; Kim, Myung-Sunny

    2016-09-01

    Natural compounds that regulate peroxisome proliferator-activated receptor alpha (PPARα) have been reported to have beneficial effects in obesity-mediated metabolic disorders. In this study, we demonstrated that biochanin A (BA), an agonist of PPAR-α, improved hepatic steatosis and insulin resistance by regulating hepatic lipid and glucose metabolism. C57BL/6 mice were fed a normal chow diet, a high-fat diet (HFD), and an HFD supplemented with 0.05% BA for 12 weeks. Histological and biochemical examinations indicated that BA prevented obesity-induced hepatic steatosis and insulin resistance in HFD-fed mice. BA stimulated the transcriptional activation of PPAR-α in vitro and increased the expression of PPAR-α and its regulatory proteins in the liver. CE-TOF/MS analyses indicated that BA administration promoted the recovery of metabolites involved in phosphatidylcholine synthesis, lipogenesis, and beta-oxidation in the livers of obese mice. BA also suppressed the levels of gluconeogenesis-related metabolites and the expression of the associated enzymes, glucose 6-phosphatase and pyruvate kinase. Taken together, these results showed that BA ameliorated metabolic disorders such as hepatic steatosis and insulin resistance by modulating lipid and glucose metabolism in diet-induced obesity. Thus, BA may be a potential therapeutic agent for the prevention of obesity-mediated hepatic steatosis and insulin resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Public utility regulation and national energy policy

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, P.

    1980-09-01

    The linkage between Public Utility Commission (PUC) regulation, the deteriorating financial health of the electric utility industry, and implementation of national energy policy, particularly the reduction of foreign petroleum consumption in the utility sector is examined. The role of the Nation's utilities in the pursuit of national energy policy goals and postulates a linkage between PUC regulation, the poor financial health of the utility industry, and the current and prospective failure to displace foreign petroleum in the utility sector is discussed. A brief history of PUC regulation is provided. The concept of regulatory climate and how the financial community has developed a system of ranking regulatory climate in the various State jurisdictions are explained. The existing evidence on the hypothesis that the cost of capital to a utility increases and its availability is reduced as regulatory climate grows more unfavorable from an investor's point of view is analyzed. The implications of this cost of capital effect on the electric utilities and collaterally on national energy policy and electric ratepayers are explained. Finally various State, regional and Federal regulatory responses to problems associated with PUC regulation are examined.

  7. Hepatitis B X-interacting protein promotes cisplatin resistance and regulates CD147 via Sp1 in ovarian cancer.

    Science.gov (United States)

    Zou, Wei; Ma, Xiangdong; Yang, Hong; Hua, Wei; Chen, Biliang; Cai, Guoqing

    2017-03-01

    Ovarian cancer is the highest mortality rate of all female reproductive malignancies. Drug resistance is a major cause of treatment failure in malignant tumors. Hepatitis B X-interacting protein acts as an oncoprotein, regulates cell proliferation, and migration in breast cancer. We aimed to investigate the effects and mechanisms of hepatitis B X-interacting protein on resistance to cisplatin in human ovarian cancer cell lines. The mRNA and protein levels of hepatitis B X-interacting protein were detected using RT-PCR and Western blotting in cisplatin-resistant and cisplatin-sensitive tissues, cisplatin-resistant cell lines A2780/CP and SKOV3/CP, and cisplatin-sensitive cell lines A2780 and SKOV3. Cell viability and apoptosis were measured to evaluate cellular sensitivity to cisplatin in A2780/CP cells. Luciferase reporter gene assay was used to determine the relationship between hepatitis B X-interacting protein and CD147. The in vivo function of hepatitis B X-interacting protein on tumor burden was assessed in cisplatin-resistant xenograft models. The results showed that hepatitis B X-interacting protein was highly expressed in ovarian cancer of cisplatin-resistant tissues and cells. Notably, knockdown of hepatitis B X-interacting protein significantly reduced cell viability in A2780/CP compared with cisplatin treatment alone. Hepatitis B X-interacting protein and cisplatin cooperated to induce apoptosis and increase the expression of c-caspase 3 as well as the Bax/Bcl-2 ratio. We confirmed that hepatitis B X-interacting protein up-regulated CD147 at the protein expression and transcriptional levels. Moreover, we found that hepatitis B X-interacting protein was able to activate the CD147 promoter through Sp1. In vivo, depletion of hepatitis B X-interacting protein decreased the tumor volume and weight induced by cisplatin. Taken together, these results indicate that hepatitis B X-interacting protein promotes cisplatin resistance and regulated CD147 via Sp1 in

  8. Self-regulating energy storage system

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhaure, D.B.; Downer, J.R.; Bliamptis, T.E.; Oberbeck, G.A.; Hendrie, S.D.

    1986-10-14

    This patent describes a self-regulating energy storage system which consists of: an a.c. motor/generator including a rotor; a flywheel attached to the motor/generator; means for monitoring the position of the motor/generator rotor; means for resolving current to and from the motor/generator; a pulse width modulated bidirectional inverter interconnecting the motor/generator with a power supply bus having a voltage to be regulated; a summing circuit for determining differences between a reference voltage and the voltage on the power supply bus to be regulated; and a pulse width modulation switch control responsive to the summing circuit, to the means for monitoring, and to the means for resolving.

  9. Hypolipidemic effect of dietary pea proteins: Impact on genes regulating hepatic lipid metabolism.

    Science.gov (United States)

    Rigamonti, Elena; Parolini, Cinzia; Marchesi, Marta; Diani, Erika; Brambilla, Stefano; Sirtori, Cesare R; Chiesa, Giulia

    2010-05-01

    Controversial data on the lipid-lowering effect of dietary pea proteins have been provided and the mechanisms behind this effect are not completely understood. The aim of the study was to evaluate a possible hypolipidemic activity of a pea protein isolate and to determine whether pea proteins could affect the hepatic lipid metabolism through regulation of genes involved in cholesterol and fatty acid homeostasis. Rats were fed Nath's hypercholesterolemic diets for 28 days, the protein sources being casein or a pea protein isolate from Pisum sativum. After 14 and 28 days of dietary treatment, rats fed pea proteins had markedly lower plasma cholesterol and triglyceride levels than rats fed casein (pPea protein-fed rats displayed higher hepatic mRNA levels of LDL receptor versus those fed casein (ppea protein-fed rats than in rats fed casein (ppea proteins in rats. Moreover, pea proteins appear to affect cellular lipid homeostasis by upregulating genes involved in hepatic cholesterol uptake and by downregulating fatty acid synthesis genes.

  10. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress

    OpenAIRE

    Zhang, Chunbin; Wang, Guohui; Zheng, Ze; Maddipati, Krishna Rao; Zhang, Xuebao; Dyson, Gregory; Williams, Paul; Duncan, Stephen A.; Kaufman, Randal J.; Zhang, Kezhong

    2012-01-01

    CREBH is a liver-specific transcription factor that is localized in the endoplasmic reticulum (ER) membrane. Our previous work demonstrated that CREBH is activated by ER stress or inflammatory stimuli to induce an acute-phase hepatic inflammation. Here we demonstrate that CREBH is a key metabolic regulator of hepatic lipogenesis, fatty acid (FA) oxidation, and lipolysis under metabolic stress. Saturated FA, insulin signals, or an atherogenic high-fat diet can induce CREBH activation in the li...

  11. Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way

    Energy Technology Data Exchange (ETDEWEB)

    Marmugi, Alice; Lukowicz, Céline; Lasserre, Frederic; Montagner, Alexandra; Polizzi, Arnaud; Ducheix, Simon; Goron, Adeline; Gamet-Payrastre, Laurence [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France); Gerbal-Chaloin, Sabine [Institute of Regenerative Medicine and Biotherapy, INSERM, U1183 Montpellier (France); Pascussi, Jean Marc [Centre National de la Recherche Scientifique, UMR5203, Institut de Génomique Fonctionnelle, Montpellier (France); Moldes, Marthe [Centre de Recherche Saint-Antoine, INSERM, UMR 938, Sorbonne Universités, Université Paris 6, Paris (France); Institut Hospitalo-Universitaire ICAN, Paris (France); Pineau, Thierry; Guillou, Hervé [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France); Mselli-Lakhal, Laila, E-mail: laila.lakhal@toulouse.inra.fr [INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse (France); Université de Toulouse, INP, UPS, TOXALIM, Toulouse (France)

    2016-07-15

    The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are still unknown. This work aimed to investigate the effect of CAR activation on hepatic energy metabolism during physiological conditions, i.e. in mouse models not subjected to metabolic/nutritional stress. Gene expression profiling in the liver of CAR knockout and control mice on chow diet and treated with a CAR agonist highlighted CAR-mediated up-regulations of lipogenic genes, concomitant with neutral lipid accumulation. A strong CAR-mediated up-regulation of the patatin-like phospholipase domain-containing protein 3 (Pnpla3) was demonstrated. Pnpla3 is a gene whose polymorphism is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) development. This observation was confirmed in human hepatocytes treated with the antiepileptic drug and CAR activator, phenobarbital and in immortalized human hepatocytes treated with CITCO. Studying the molecular mechanisms controlling Pnpla3 gene expression, we demonstrated that CAR does not act by a direct regulation of Pnpla3 transcription or via the Liver X Receptor but may rather involve the transcription factor Carbohydrate Responsive Element-binding protein. These data provide new insights into the regulation by CAR of glycolytic and lipogenic genes and on pathogenesis of steatosis. This also raises the question concerning the impact of drugs and environmental contaminants in lipid-associated metabolic diseases. - Highlights: • Induction of hepatic glycolytic and lipogenic genes upon CAR activation by TCPOBOP. • These effects are not mediated by the nuclear receptor LXR. • CAR activation resulted in hepatic lipid accumulation. • Pnpla3 expression is regulated by CAR in mouse liver and

  12. Activation of the Constitutive Androstane Receptor induces hepatic lipogenesis and regulates Pnpla3 gene expression in a LXR-independent way

    International Nuclear Information System (INIS)

    Marmugi, Alice; Lukowicz, Céline; Lasserre, Frederic; Montagner, Alexandra; Polizzi, Arnaud; Ducheix, Simon; Goron, Adeline; Gamet-Payrastre, Laurence; Gerbal-Chaloin, Sabine; Pascussi, Jean Marc; Moldes, Marthe; Pineau, Thierry; Guillou, Hervé; Mselli-Lakhal, Laila

    2016-01-01

    The Constitutive Androstane Receptor (CAR, NR1I3) has been newly described as a regulator of energy metabolism. A relevant number of studies using animal models of obesity suggest that CAR activation could be beneficial on the metabolic balance. However, this remains controversial and the underlying mechanisms are still unknown. This work aimed to investigate the effect of CAR activation on hepatic energy metabolism during physiological conditions, i.e. in mouse models not subjected to metabolic/nutritional stress. Gene expression profiling in the liver of CAR knockout and control mice on chow diet and treated with a CAR agonist highlighted CAR-mediated up-regulations of lipogenic genes, concomitant with neutral lipid accumulation. A strong CAR-mediated up-regulation of the patatin-like phospholipase domain-containing protein 3 (Pnpla3) was demonstrated. Pnpla3 is a gene whose polymorphism is associated with the pathogenesis of nonalcoholic fatty liver disease (NAFLD) development. This observation was confirmed in human hepatocytes treated with the antiepileptic drug and CAR activator, phenobarbital and in immortalized human hepatocytes treated with CITCO. Studying the molecular mechanisms controlling Pnpla3 gene expression, we demonstrated that CAR does not act by a direct regulation of Pnpla3 transcription or via the Liver X Receptor but may rather involve the transcription factor Carbohydrate Responsive Element-binding protein. These data provide new insights into the regulation by CAR of glycolytic and lipogenic genes and on pathogenesis of steatosis. This also raises the question concerning the impact of drugs and environmental contaminants in lipid-associated metabolic diseases. - Highlights: • Induction of hepatic glycolytic and lipogenic genes upon CAR activation by TCPOBOP. • These effects are not mediated by the nuclear receptor LXR. • CAR activation resulted in hepatic lipid accumulation. • Pnpla3 expression is regulated by CAR in mouse liver and

  13. Background and objectives of energy regulation

    International Nuclear Information System (INIS)

    Ailleret, F.

    2002-01-01

    The concept of sustainable development is now a common reference for governments and businesses, for institutions and associations of all kinds. Sustainable development is founded on three inseparable pillars: economic growth, respect for the natural environment and social progress. Energy is vital for economic growth, and though it may be harmful to the environment it is also a source of new solutions. Indeed, to achieve a decent quality of life, individuals and communities must have easy access to different energy forms, though this is regrettably not the case for one-third of humanity. Clearly, energy and sustainable development are closely linked and the organization of energy systems must take this essential relation into account. It is the duty of each state - or group of states, such as the European Union - to define its energy policy. Market forces alone are not sufficient to keep the system in balance, so effective regulation is vital. The theme of the 11th Forum concerns a crucial question and this meeting offers a welcome opportunity for debate at a time when market liberalisation is spreading through the energy sector on a world-wide scale. For gas and electricity especially, it is causing a tidal wave of change and rendering our old regulatory systems obsolete. Though this review of regulatory questions will serve to define practical measures for implementation in the short term, it should also give consideration to the key trends in energy growth, the provisions laid down in the Kyoto protocol and the dramatic inequalities across the world regarding access to energy. Likewise, it is important to identify the challenges, risks and constraints that must be taken into account to ensure that as our energy systems evolve, they contribute to progress in economic development, environmental protection and quality of life. (author)

  14. Innovation, Diffusion, and Regulation in Energy Technologies

    Science.gov (United States)

    Fetter, Theodore Robert

    The innovation and diffusion of new technologies is one of the central concerns of economics. New inventions or technological combinations do not spring fully formed into the world; as firms encounter and learn about new technologies they experiment, refine, and learn about them, improving productivity (and sometimes earning economic rents). Understanding the processes by which firms learn, and how these processes interact with regulations, is fundamental to understanding the emergence of new technologies, their contribution to growth, and the interaction of innovation and regulation. This dissertation addresses how firms learn and respond to regulations in the context of emerging technologies. Within this framework, I address several questions. When production inputs are socially controversial, do firms respond to disclosure laws by voluntarily constraining their inputs? Do these public disclosure laws facilitate knowledge transmission across firms, and if so, what are the implications for public welfare - for instance, do the gains from trade outweigh any effects of reduced incentives for innovation? I study these questions in the context of hydraulic fracturing, though the results offer insight for more general settings. Panning out to a much broader view, I also explore how energy-related technologies - in both generation and consumption - diffuse across national boundaries over time, and whether innovation and diffusion of energy-efficient technologies has led to more or less energy-efficient economic growth. In my first paper, I contribute to improved understanding of the conditions in which information-based regulations, which are increasingly common in multiple policy domains, decrease externalities such as environmental pollution. Specifically, I test whether information disclosure regulations applied to hydraulic fracturing chemicals caused firms to decrease their use of toxic inputs. Prior to these mandatory disclosure laws, some operators voluntarily

  15. Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

    Science.gov (United States)

    Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

    2017-10-01

    Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

  16. Regulation of Porcine Hepatic Cytochrome P450 — Implication for Boar Taint

    Directory of Open Access Journals (Sweden)

    Martin Krøyer Rasmussen

    2014-09-01

    Full Text Available Cytochrome P450 (CYP450 is the major family of enzymes involved in the metabolism of several xenobiotic and endogenous compounds. Among substrates for CYP450 is the tryptophan metabolite skatole (3-methylindole, one of the major contributors to the off-odour associated with boar-tainted meat. The accumulation of skatole in pigs is highly dependent on the hepatic clearance by CYP450s. In recent years, the porcine CYP450 has attracted attention both in relation to meat quality and as a potential model for human CYP450. The molecular regulation of CYP450 mRNA expression is controlled by several nuclear receptors and transcription factors that are targets for numerous endogenously and exogenously produced agonists and antagonists. Moreover, CYP450 expression and activity are affected by factors such as age, gender and feeding. The regulation of porcine CYP450 has been suggested to have more similarities with human CYP450 than other animal models, including rodents. This article reviews the available data on porcine hepatic CYP450s and its implications for boar taint.

  17. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

    Science.gov (United States)

    Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

    1994-11-15

    Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

  19. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.

    Science.gov (United States)

    Watashi, Koichi; Ishii, Naoto; Hijikata, Makoto; Inoue, Daisuke; Murata, Takayuki; Miyanari, Yusuke; Shimotohno, Kunitada

    2005-07-01

    Viruses depend on host-derived factors for their efficient genome replication. Here, we demonstrate that a cellular peptidyl-prolyl cis-trans isomerase (PPIase), cyclophilin B (CyPB), is critical for the efficient replication of the hepatitis C virus (HCV) genome. CyPB interacted with the HCV RNA polymerase NS5B to directly stimulate its RNA binding activity. Both the RNA interference (RNAi)-mediated reduction of endogenous CyPB expression and the induced loss of NS5B binding to CyPB decreased the levels of HCV replication. Thus, CyPB functions as a stimulatory regulator of NS5B in HCV replication machinery. This regulation mechanism for viral replication identifies CyPB as a target for antiviral therapeutic strategies.

  20. Effect of trans-chalcone on hepatic IL-8 through the regulation of miR-451 in male rats

    Directory of Open Access Journals (Sweden)

    Karimi-Sales Elham

    2018-01-01

    Full Text Available Objective. Trans-chalcone is a chalcone with hepatoprotective and anti-inflammatory effects. However, the mechanism of these positive effects, especially on miR-451 as an inflammatory regulator, is poorly understood. In this regard, this microRNA (miRNA acts by inhibition of hepatic interleukin-8 (IL-8 production in the liver which is one of the main proinflammatory cytokines. Th is study for the first time examined the effect of trans-chalcone on miR-451/IL-8 pathway. Methods. In present study, 21 male rats were randomly divided into 3 groups (n=7 per each group: control which received solvent (NS, groups 2 (N2T and 3 (N6T, which received transchalcone for 2 and 6 weeks, respectively. Hepatic level of miR-451 was measured by qRT-PCR. Serum levels of alanine aminotransferase (ALT and aspartate aminotransferase (AST as well as hepatic level of IL-8 protein were measured. Results. Trans-chalcone decreased hepatic level of IL-8 protein and serum level of ALT aft er 2 weeks of treatment without significant change in hepatic miR-451. Moreover, it increased hepatic level of miR-451 and reduced hepatic IL-8 as well as AST and ALT aft er 6 weeks. Conclusion. Based on the results of present study, miR-451/IL-8 pathway is a possible mechanism for hepatoprotective action of trans-chalcone in long-term.

  1. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

    Science.gov (United States)

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-03-11

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

  2. Regulation of energy homeostasis via GPR120

    Directory of Open Access Journals (Sweden)

    Atsuhiko eIchimura

    2014-07-01

    Full Text Available Free fatty acids (FFAs are fundamental units of key nutrients. FFAs exert various biological functions, depending on the chain length and degree of desaturation. Recent studies have shown that several FFAs act as ligands of G-protein-coupled receptors (GPCRs, activate intracellular signaling and exert physiological functions via these GPCRs. GPR120 (also known as free fatty acid receptor 4, FFAR4 is activated by unsaturated medium- to long-chain FFAs and has a critical role in various physiological homeostasis mechanisms such as incretin hormone secretion, food preference, anti-inflammation and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat in white adipose tissue and regulates the whole body energy homeostasis in both humans and rodents. Genetic study in human identified the loss-of-functional mutation of GPR120 associated with obesity and insulin resistance. In addition, dysfunction of GPR120 has been linked as a novel risk factor for diet-induced obesity. This review aims to provide evidence from the recent development in physiological function of GPR120 and discusses its functional roles in regulation of energy homeostasis and its potential as drug targets.

  3. MicroRNA-451 Negatively Regulates Hepatic Glucose Production and Glucose Homeostasis by Targeting Glycerol Kinase-Mediated Gluconeogenesis.

    Science.gov (United States)

    Zhuo, Shu; Yang, Mengmei; Zhao, Yanan; Chen, Xiaofang; Zhang, Feifei; Li, Na; Yao, Pengle; Zhu, Tengfei; Mei, Hong; Wang, Shanshan; Li, Yu; Chen, Shiting; Le, Yingying

    2016-11-01

    MicroRNAs (miRNAs) are a new class of regulatory molecules implicated in type 2 diabetes, which is characterized by insulin resistance and hepatic glucose overproduction. We show that miRNA-451 (miR-451) is elevated in the liver tissues of dietary and genetic mouse models of diabetes. Through an adenovirus-mediated gain- and loss-of-function study, we found that miR-451 negatively regulates hepatic gluconeogenesis and blood glucose levels in normal mice and identified glycerol kinase (Gyk) as a direct target of miR-451. We demonstrate that miR-451 and Gyk regulate hepatic glucose production, the glycerol gluconeogenesis axis, and the AKT-FOXO1-PEPCK/G6Pase pathway in an opposite manner; Gyk could reverse the effect of miR-451 on hepatic gluconeogenesis and AKT-FOXO1-PEPCK/G6Pase pathway. Moreover, overexpression of miR-451 or knockdown of Gyk in diabetic mice significantly inhibited hepatic gluconeogenesis, alleviated hyperglycemia, and improved glucose tolerance. Further studies showed that miR-451 is upregulated by glucose and insulin in hepatocytes; the elevation of hepatic miR-451 in diabetic mice may contribute to inhibiting Gyk expression. This study provides the first evidence that miR-451 and Gyk regulate the AKT-FOXO1-PEPCK/G6Pase pathway and play critical roles in hepatic gluconeogenesis and glucose homeostasis and identifies miR-451 and Gyk as potential therapeutic targets against hyperglycemia in diabetes. © 2016 by the American Diabetes Association.

  4. Loss of regulator of G protein signaling 5 exacerbates obesity, hepatic steatosis, inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Wei Deng

    Full Text Available BACKGROUND: The effect of regulator of G protein signaling 5 (RGS5 on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC or a high-fat diet (HF. METHODOLOGY/PRINCIPAL FINDINGS: Male, 8-week-old RGS5 knockout (KO and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance.

  5. The role of regulation in Europe's energy markets

    International Nuclear Information System (INIS)

    Jones, Ch.

    2005-01-01

    In this paper, the author emphasizes the two main issues of the role of a regulation authority in the de-regulated European internal energy markets: regulation and competition and regulation and security of supply. He explains the manner in which the European Commission will organize the preparation of new or revised guidelines under the regulation. (J.S.)

  6. A review of building energy regulation and policy for energy conservation in developing countries

    International Nuclear Information System (INIS)

    Iwaro, Joseph; Mwasha, Abraham

    2010-01-01

    The rapid growth of energy use, worldwide, hfs raised concerns over problems of energy supply and exhaustion of energy resources. Most of the developed countries are implementing building energy regulations such as energy standards, codes etc., to reduce building energy consumption. The position of developing countries with respect to energy regulations implementation and enforcement is either poorly documented or not documented at all. In addition, there is a lack of consistent data, which makes it difficult to understand the underlying changes that affect energy regulation implementation in developing countries. In that respect, this paper investigates the progress of building energy regulations in developing countries and its implication for energy conservation and efficiency. The present status of building energy regulations in 60 developing countries around the world was analysed through a survey of building energy regulations using online survey. The study revealed the present progress made on building energy regulations in relation to implementation, development and compliance; at the same time the study recommends possible solutions to the barriers facing building energy regulation implementation in the developing world. - Research Highlights: →Progress and implications of energy regulations in developing countries. →Investigation assessed the progress made on energy regulations using online survey. →Energy regulation activities is progressively increasing in developing countries. →The study identified 25 developing countries without energy regulatory standards. →The study shows relationship between energy regulation and energy consumption.

  7. Organization and regulation of energy markets in the European Union

    International Nuclear Information System (INIS)

    Vasconcelos, J.

    2002-01-01

    The energy regulation policy and the organization of power matters in the European Union as well as the energy markets are discussed in this Keynote Paper. The Council of European Energy Regulators is introduced. The goal of the European Union regarding energy generation and consumption in the future are analyzed. (R.P.)

  8. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism

    DEFF Research Database (Denmark)

    Caesar, Robert; Nygren, Heli; Orešič, Matej

    2016-01-01

    The gut microbiota influences many aspects of host metabolism. We have previously shown that the presence of a gut microbiota remodels lipid composition. Here we investigated how interaction between gut microbiota and dietary lipids regulates lipid composition in the liver and plasma, and gene...... of most lipid classes differed between mice fed lard and fish oil. However, the gut microbiota also affected lipid composition. The gut microbiota increased hepatic levels of cholesterol and cholesteryl esters in mice fed lard, but not in mice fed fish oil. Serum levels of cholesterol and cholesteryl...... esters were not affected by the gut microbiota. Genes encoding enzymes involved in cholesterol biosynthesis were downregulated by the gut microbiota in mice fed lard and were expressed at a low level in mice fed fish oil independent of microbial status. In summary, we show that gut microbiota...

  9. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  10. Stearoyl coenzyme A desaturase 1 is associated with hepatitis C virus replication complex and regulates viral replication

    DEFF Research Database (Denmark)

    Nguyen, LN; Lim, YS; Pham, Long

    2014-01-01

    The hepatitis C virus (HCV) life cycle is tightly regulated by lipid metabolism of host cells. In order to identify host factors involved in HCV propagation, we have recently screened a small interfering RNA (siRNA) library targeting host genes that control lipid metabolism and lipid droplet...

  11. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.

    Science.gov (United States)

    Verrier, Eloi R; Colpitts, Che C; Bach, Charlotte; Heydmann, Laura; Zona, Laetitia; Xiao, Fei; Thumann, Christine; Crouchet, Emilie; Gaudin, Raphaël; Sureau, Camille; Cosset, François-Loïc; McKeating, Jane A; Pessaux, Patrick; Hoshida, Yujin; Schuster, Catherine; Zeisel, Mirjam B; Baumert, Thomas F

    2016-10-25

    Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  12. Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

    Directory of Open Access Journals (Sweden)

    Eloi R. Verrier

    2016-10-01

    Full Text Available Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs, including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies.

  13. Proceedings of the 8. Brazilian congress on energy: energy policy, regulation and sustainable development. v. 1: energy, environment and energy sector regulation

    International Nuclear Information System (INIS)

    1999-01-01

    The theme energy policy, regulation and sustainable development chosen for the 8. Brazilian congress on energy to be held in Rio de Janeiro from 30 November of 1999 to 02 December of 1999, specifically means the contribution of energy to a satisfactory quality of life for everyone. Within such a context, the congress technical programme theme has been structured around six different divisions: energy, environment and development; energy sector regulation; energy policy and planning; technology innovation; energy conservation; and renewable energy sources and rural areas energy supply

  14. Ethanol negatively regulates hepatic differentiation of hESC by inhibition of the MAPK/ERK signaling pathway in vitro.

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available Alcohol insult triggers complex events in the liver, promoting fibrogenic/inflammatory signals and in more advanced cases, aberrant matrix deposition. It is well accepted that the regenerative capacity of the adult liver is impaired during alcohol injury. The liver progenitor/stem cells have been shown to play an important role in liver regeneration -in response to various chronic injuries; however, the effects of alcohol on stem cell differentiation in the liver are not well understood.We employed hepatic progenitor cells derived from hESCs to study the impact of ethanol on hepatocyte differentiation by exposure of these progenitor cells to ethanol during hepatocyte differentiation.We found that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitor cells in a dose-dependent manner. There was also a moderate cell cycle arrest at G1/S checkpoint in the ethanol treated cells, which is associated with a reduced level of cyclin D1 in these cells. Ethanol treatment specifically inhibited the activation of the ERK but not JNK nor the p38 MAP signaling pathway. At the same time, the WNT signaling pathway was also reduced in the cells exposed to ethanol. Upon evaluating the effects of the inhibitors of these two signaling pathways, we determined that the Erk inhibitor replicated the effects of ethanol on the hepatocyte differentiation and attenuated the WNT/β-catenin signaling, however, inhibitors of WNT only partially replicated the effects of ethanol on the hepatocyte differentiation.Our results demonstrated that ethanol negatively regulated hepatic differentiation of hESC-derived hepatic progenitors through inhibiting the MAPK/ERK signaling pathway, and subsequently attenuating the WNT signaling pathway. Thus, our finding provides a novel insight into the mechanism by which alcohol regulates cell fate selection of hESC-derived hepatic progenitor cells, and the identified pathways may provide therapeutic targets

  15. Regulation of hepatic level of fatty-acid-binding protein by hormones and clofibric acid in the rat.

    Science.gov (United States)

    Nakagawa, S; Kawashima, Y; Hirose, A; Kozuka, H

    1994-01-01

    Regulation of the hepatic level of fatty-acid-binding protein (FABP) by hormones and p-chlorophenoxyisobutyric acid (clofibric acid) was studied. The hepatic level of FABP, measured as the oleic acid-binding capacity of the cytosolic FABP fraction, was decreased in streptozotocin-diabetic rats. The level of FABP was markedly increased in adrenalectomized rats, and the elevation was prevented by the administration of dexamethasone. Hypothyroidism decreased the level of FABP and hyperthyroidism increased it. A high correlation between the incorporation of [14C]oleic acid in vivo into hepatic triacylglycerol and the level of FABP was found for normal, diabetic and adrenalectomized rats. The level of FABP was increased by administration of clofibric acid to rats in any altered hormonal states, as was microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase, a peroxisome-proliferator-responsive parameter. These results suggest that the hepatic level of FABP is under regulation by multiple hormones and that clofibric acid induces FABP and 1-acyl-GPC acyltransferase by a mechanism which may be distinct from that by which hormones regulate the level of FABP. PMID:8110197

  16. The epigenetic regulation of stem cell factors in hepatic stellate cells.

    Science.gov (United States)

    Reister, Sven; Kordes, Claus; Sawitza, Iris; Häussinger, Dieter

    2011-10-01

    The epigenetic regulation by DNA methylation is an important mechanism to control the expression of stem cell factors as demonstrated in tumor cells. It was recently shown that hepatic stellate cells (HSC) express stem/progenitor cell factors and have a differentiation potential. The aim of this work was to investigate if the expression of stem cell markers is regulated by DNA methylation during activation of rat HSC. It was found that CD133, Notch1, and Notch3 are regulated via DNA methylation in HSC, whereas Nestin shows no DNA methylation in HSC and other undifferentiated cells such as embryonic stem cells and umbilical cord blood stem cells from rats. In contrast to this, DNA methylation controls Nestin expression in differentiated cells like hepatocytes and the hepatoma cell line H4IIE. Demethylation by 5-Aza-2-deoxycytidine was sufficient to induce Nestin in H4IIE cells. In quiescent stellate cells and embryonic stem cells, the Nestin expression was suppressed by histone H3 methylation at lysine 9, which is another epigenetic mechanism. Apart from the known induction of Nestin in cultured HSC, this intermediate filament protein was also induced after partial hepatectomy, indicating activation of HSC during liver regeneration. Taken together, this study demonstrates for the first time that the expression of stem cell-associated factors such as CD133, Notch1, and Notch3 is controlled by DNA methylation in HSC. The regulation of Nestin by DNA methylation seems to be restricted to differentiated cells, whereas undifferentiated cells use different epigenetic mechanisms such as histone H3 methylation to control Nestin expression.

  17. Curcumin inhibits hepatitis B virus infection by down-regulating cccDNA-bound histone acetylation.

    Science.gov (United States)

    Wei, Zhi-Qiang; Zhang, Yong-Hong; Ke, Chang-Zheng; Chen, Hong-Xia; Ren, Pan; He, Yu-Lin; Hu, Pei; Ma, De-Qiang; Luo, Jie; Meng, Zhong-Ji

    2017-09-14

    To investigate the potential effect of curcumin on hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and the underlying mechanism. A HepG2.2.15 cell line stably transfected with HBV was treated with curcumin, and HBV surface antigen (HBsAg) and e antigen (HBeAg) expression levels were assessed by ELISA. Intracellular HBV DNA replication intermediates and cccDNA were detected by Southern blot and real-time PCR, respectively. The acetylation levels of histones H3 and H4 were measured by Western blot. H3/H4-bound cccDNA was detected by chromatin immunoprecipitation (ChIP) assays. The deacetylase inhibitors trichostatin A and sodium butyrate were used to study the mechanism of action for curcumin. Additionally, short interfering RNAs (siRNAs) targeting HBV were tested along with curcumin. Curcumin treatment led to time- and dose-dependent reductions in HBsAg and HBeAg expression and significant reductions in intracellular HBV DNA replication intermediates and HBV cccDNA. After treatment with 20 μmol/L curcumin for 2 d, HBsAg and cccDNA levels in HepG2.2.15 cells were reduced by up to 57.7% ( P curcumin, accompanied by reductions in H3- and H4-bound cccDNA. Furthermore, the deacetylase inhibitors trichostatin A and sodium butyrate could block the effects of curcumin. Additionally, transfection of siRNAs targeting HBV enhanced the inhibitory effects of curcumin. Curcumin inhibits HBV gene replication via down-regulation of cccDNA-bound histone acetylation and has the potential to be developed as a cccDNA-targeting antiviral agent for hepatitis B.

  18. Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

    Directory of Open Access Journals (Sweden)

    Nicolai J. Wewer Albrechtsen

    2017-11-01

    Full Text Available Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61 appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in vivo. We conclude that glucagon variants, such as PG 1-61, may contribute to glucose regulation by stimulating hepatic glucose production and insulin secretion.

  19. Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

    Science.gov (United States)

    Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

    2004-07-01

    Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to

  20. Sildenafil protects against bile duct ligation induced hepatic fibrosis in rats: Potential role for silent information regulator 1 (SIRT1).

    Science.gov (United States)

    Abd El Motteleb, Dalia M; Ibrahim, Islam A A E-H; Elshazly, Shimaa M

    2017-11-15

    Hepatic fibrosis is a potential health problem that may end with life-threatening cirrhosis and primary liver cancer. Recent studies point out to the protective effects of silent information regulator1 (SIRT1), against different models of organs fibrosis. This work aimed to investigate the possible protective effect of sildenafil (SIRT1 activator) against hepatic fibrosis induced by bile duct ligation (BDL). Firstly, three different doses of sildenafil (5, 10, 20mg/kg/day) were investigated; to detect the most protective one against BDL induced liver dysfunction and hepatic fibrosis. The most protective dose is then used; to study its effect on BDL induced SIRT1 downregulation, imbalance of oxidant/antioxidant status, increased inflammatory cytokines and fibrosis. Sildenafil (20mg/kg/day) was the most protective one, it caused upregulation of SIRT1, reduction of hepatic malondialdehyde (MDA) content, increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenease (HO)-1, reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Hepatic content of tumor necrosis factor-α (TNF-α) and nuclear factor κB (NFκB) expression & content displayed significant reductions with sildenafil treatment, Furthermore, sildenafil caused marked reductions of transforming growth factor (TGF)-β content, expression of plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), α-smooth muscle actin (α-SMA), fibronectin, collagen I (α1) and hydroxyproline content. However, sildenafil protective effects were significantly reduced by co-administration of EX527 (SIRT1 inhibitor). Our work showed, for the first time that, sildenafil has promising protective effects against BDL induced liver dysfunction and hepatic fibrosis. These effects may be, in part, mediated by up regulation of SIRT1. Copyright © 2017. Published by Elsevier Inc.

  1. DYRK1A Is a Regulator of S-Phase Entry in Hepatic Progenitor Cells.

    Science.gov (United States)

    Kruitwagen, Hedwig S; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda J; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

    2018-01-15

    Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage, HPC proliferation is triggered by external activation mechanisms from their niche. Although several important proproliferative mechanisms have been described, it is not known which key intracellular regulators govern the switch between HPC quiescence and active cell cycle. We performed a high-throughput kinome small interfering RNA (siRNA) screen in HepaRG cells, a HPC-like cell line, and evaluated the effect on proliferation with a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. One hit increased the percentage of EdU-positive cells after knockdown: dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A). Although upon DYRK1A silencing, the percentage of EdU- and phosphorylated histone H3 (pH3)-positive cells was increased, and total cell numbers were not increased, possibly through a subsequent delay in cell cycle progression. This phenotype was confirmed with chemical inhibition of DYRK1A using harmine and with primary HPCs cultured as liver organoids. DYRK1A inhibition impaired Dimerization Partner, RB-like, E2F, and multivulva class B (DREAM) complex formation in HPCs and abolished its transcriptional repression on cell cycle progression. To further analyze DYRK1A function in HPC proliferation, liver organoid cultures were established from mBACtgDyrk1A mice, which harbor one extra copy of the murine Dyrk1a gene (Dyrk+++). Dyrk+++ organoids had both a reduced percentage of EdU-positive cells and reduced proliferation compared with wild-type organoids. This study provides evidence for an essential role of DYRK1A as balanced regulator of S-phase entry in HPCs. An exact gene dosage is crucial, as both DYRK1A deficiency and overexpression affect HPC cell cycle progression.

  2. Endocytosis of collagen by hepatic stellate cells regulates extracellular matrix dynamics.

    Science.gov (United States)

    Bi, Yan; Mukhopadhyay, Dhriti; Drinane, Mary; Ji, Baoan; Li, Xing; Cao, Sheng; Shah, Vijay H

    2014-10-01

    Hepatic stellate cells (HSCs) generate matrix, which in turn may also regulate HSCs function during liver fibrosis. We hypothesized that HSCs may endocytose matrix proteins to sense and respond to changes in microenvironment. Primary human HSCs, LX2, or mouse embryonic fibroblasts (MEFs) [wild-type; c-abl(-/-); or Yes, Src, and Fyn knockout mice (YSF(-/-))] were incubated with fluorescent-labeled collagen or gelatin. Fluorescence-activated cell sorting analysis and confocal microscopy were used for measuring cellular internalization of matrix proteins. Targeted PCR array and quantitative real-time PCR were used to evaluate gene expression changes. HSCs and LX2 cells endocytose collagens in a concentration- and time-dependent manner. Endocytosed collagen colocalized with Dextran 10K, a marker of macropinocytosis, and 5-ethylisopropyl amiloride, an inhibitor of macropinocytosis, reduced collagen internalization by 46%. Cytochalasin D and ML7 blocked collagen internalization by 47% and 45%, respectively, indicating that actin and myosin are critical for collagen endocytosis. Wortmannin and AKT inhibitor blocked collagen internalization by 70% and 89%, respectively, indicating that matrix macropinocytosis requires phosphoinositide-3-kinase (PI3K)/AKT signaling. Overexpression of dominant-negative dynamin-2 K44A blocked matrix internalization by 77%, indicating a role for dynamin-2 in matrix macropinocytosis. Whereas c-abl(-/-) MEF showed impaired matrix endocytosis, YSF(-/-) MEF surprisingly showed increased matrix endocytosis. It was also associated with complex gene regulations that related with matrix dynamics, including increased matrix metalloproteinase 9 (MMP-9) mRNA levels and zymographic activity. HSCs endocytose matrix proteins through macropinocytosis that requires a signaling network composed of PI3K/AKT, dynamin-2, and c-abl. Interaction with extracellular matrix regulates matrix dynamics through modulating multiple gene expressions including MMP-9

  3. Image quality comparison between single energy and dual energy CT protocols for hepatic imaging

    International Nuclear Information System (INIS)

    Yao, Yuan; Pelc, Norbert J.; Ng, Joshua M.; Megibow, Alec J.

    2016-01-01

    Purpose: Multi-detector computed tomography (MDCT) enables volumetric scans in a single breath hold and is clinically useful for hepatic imaging. For simple tasks, conventional single energy (SE) computed tomography (CT) images acquired at the optimal tube potential are known to have better quality than dual energy (DE) blended images. However, liver imaging is complex and often requires imaging of both structures containing iodinated contrast media, where atomic number differences are the primary contrast mechanism, and other structures, where density differences are the primary contrast mechanism. Hence it is conceivable that the broad spectrum used in a dual energy acquisition may be an advantage. In this work we are interested in comparing these two imaging strategies at equal-dose and more complex settings. Methods: We developed numerical anthropomorphic phantoms to mimic realistic clinical CT scans for medium size and large size patients. MDCT images based on the defined phantoms were simulated using various SE and DE protocols at pre- and post-contrast stages. For SE CT, images from 60 kVp through 140 with 10 kVp steps were considered; for DE CT, both 80/140 and 100/140 kVp scans were simulated and linearly blended at the optimal weights. To make a fair comparison, the mAs of each scan was adjusted to match the reference radiation dose (120 kVp, 200 mAs for medium size patients and 140 kVp, 400 mAs for large size patients). Contrast-to-noise ratio (CNR) of liver against other soft tissues was used to evaluate and compare the SE and DE protocols, and multiple pre- and post-contrasted liver-tissue pairs were used to define a composite CNR. To help validate the simulation results, we conducted a small clinical study. Eighty-five 120 kVp images and 81 blended 80/140 kVp images were collected and compared through both quantitative image quality analysis and an observer study. Results: In the simulation study, we found that the CNR of pre-contrast SE image mostly

  4. Exercise and the regulation of energy intake

    NARCIS (Netherlands)

    Scheurink, AJW; Ammar, AA; Benthem, B; van Dijk, G; Sodersten, PAT; Södersten, Per A.T.

    Energy balance is the resultant of ingested calories and energy expenditure and is generally maintained within narrow limits over prolonged periods. Exercise leads to an increase in energy expenditure which is, in the long-term, counteracted by increased energy intake. Evidence for this comes from a

  5. Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

    Directory of Open Access Journals (Sweden)

    Michael Niepmann

    2018-03-01

    Full Text Available Hepatitis C virus (HCV preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES in the 5′ untranslated region (5′ UTR, while also downstream elements like the cis-replication element (CRE in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122 binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in

  6. Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.

    Science.gov (United States)

    Niepmann, Michael; Shalamova, Lyudmila A; Gerresheim, Gesche K; Rossbach, Oliver

    2018-01-01

    Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation. The cis -elements controlling replication of the viral RNA genome are located mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis -elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3' UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis -elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis -element in question acts on HCV

  7. Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

    Science.gov (United States)

    Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

    2012-01-01

    Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by quantitative real-time PCR, reporter assay, and immunoblot analysis. In addition, saponin potentiated IFN-α-induced anti-HCV activity. Moreover, saponin exerted antiviral activity even in IFN-α resistant mutant HCVcc-infected cells. To investigate how cellular genes were regulated by saponin, we performed microarray analysis using HCVcc-infected cells. We demonstrated that suppressor of cytokine signaling 2 (SOCS2) protein level was distinctively increased by saponin, which in turn resulted in inhibition of HCV replication. We further showed that silencing of SOCS2 resurrected HCV replication and overexpression of SOCS2 suppressed HCV replication. These data imply that saponin inhibits HCV replication via SOCS2 signaling pathway. These findings suggest that saponin may be a potent therapeutic agent for HCV patients. PMID:22745742

  8. In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferators†

    Science.gov (United States)

    Guidotti, Luca G.; Eggers, Carrie M.; Raney, Anneke K.; Chi, Susan Y.; Peters, Jeffrey M.; Gonzalez, Frank J.; McLachlan, Alan

    1999-01-01

    The role of the peroxisome proliferator-activated receptor α (PPARα) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARα. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPARα but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice. PMID:10559356

  9. The metabolic sensors FXRα, PGC-1α, and SIRT1 cooperatively regulate hepatitis B virus transcription.

    Science.gov (United States)

    Curtil, Claire; Enache, Liviu S; Radreau, Pauline; Dron, Anne-Gaëlle; Scholtès, Caroline; Deloire, Alexandre; Roche, Didier; Lotteau, Vincent; André, Patrice; Ramière, Christophe

    2014-03-01

    Hepatitis B virus (HBV) genome transcription is highly dependent on liver-enriched, metabolic nuclear receptors (NRs). Among others, NR farnesoid X receptor α (FXRα) enhances HBV core promoter activity and pregenomic RNA synthesis. Interestingly, two food-withdrawal-induced FXRα modulators, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and deacetylase SIRT1, have been found to be associated with HBV genomes ex vivo. Whereas PGC-1α induction was shown to increase HBV replication, the effect of SIRT1 on HBV transcription remains unknown. Here, we showed that, in hepatocarcinoma-derived Huh-7 cells, combined activation of FXRα by GW4064 and SIRT1 by activator 3 increased HBV core promoter-controlled luciferase expression by 25-fold, compared with a 10-fold increase with GW4064 alone. Using cell lines differentially expressing FXRα in overexpression and silencing experiments, we demonstrated that SIRT1 activated the core promoter in an FXRα- and PGC-1α-dependent manner. Maximal activation (>150-fold) was observed in FXRα- and PGC-1α-overexpressing Huh-7 cells treated with FXRα and SIRT1 activators. Similarly, in cells transfected with full-length HBV genomes, maximal induction (3.5-fold) of core promoter-controlled synthesis of 3.5-kb RNA was observed in the same conditions of transfection and treatments. Thus, we identified a subnetwork of metabolic factors regulating HBV replication, strengthening the hypothesis that transcription of HBV and metabolic genes is similarly controlled.

  10. Tim-3/galectin-9 regulate the homeostasis of hepatic NKT cells in a murine model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Tang, Zhao-Hui; Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan; Li, Zhiping

    2013-02-15

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti-IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl(2)MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3(+) NKT cells are in an activated state, and Gal-9 directly induces Tim-3(+) NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3-expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9-signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD.

  11. Tim-3/Galectin-9 Regulate the Homeostasis of Hepatic NKT Cells in a Murine Model of Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Liang, Shuwen; Potter, James; Jiang, Xuan; Mao, Hai-Quan

    2013-01-01

    T cell Ig and mucin domain (Tim)-3 is well known to interact with its natural ligand, Galectin-9 (Gal-9), to regulate T cell function. However, little is known about the function of Tim-3/Gal-9 signaling in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) mediated by hepatic NKT cells that also express Tim-3. In the current study, we define the role and the mechanism of Tim-3/Gal-9 signaling in hepatic NKT cell regulation in a mouse model of diet-induced NAFLD. Adult male wild-type or CD1d knockout C57BL/6 mice were fed a high-fat diet to induce steatosis. Some of the mice also received one or a combination of Gal-9, anti–IL-15R/IL-15 mAb, rIL-15, α-galactosylceramide, and multilamellar liposomes containing Cl2MDP. The expression of Tim-3 and various markers reflecting cell proliferation, activation, cytokine production, and apoptosis was analyzed. Liver histology, steatosis grade, and hepatic triglyceride content were also evaluated. In the liver, Tim-3+ NKT cells are in an activated state, and Gal-9 directly induces Tim-3+ NKT cell apoptosis and contributes to the depletion of NKT cells in diet-induced steatosis. However, Gal-9 also interacts with Tim-3–expressing Kupffer cells to induce secretion of IL-15, thus promoting NKT cell proliferation. Exogenous administration of Gal-9 significantly ameliorates diet-induced steatosis by modulating hepatic NKT cell function. In summary, the Tim-3/Gal-9–signaling pathway plays a critical role in the homeostasis of hepatic NKT cells through activation-induced apoptosis and secondary proliferation and, thus, contributes to the pathogenesis of NAFLD. PMID:23296703

  12. Competition within the energy sector and State regulation

    International Nuclear Information System (INIS)

    Larsen, A.; Jess Olsen, O.

    1995-10-01

    It is presumed that energy markets will be liberalized. Questions discussed are how the Danish electricity and gas sectors are to be re-regulated in order to ensure that this goal is reached in the most satisfactory manner (cheaper energy supply under competitive conditions) and whether there will be a conflict between the goal of liberalization and the environmental goals of clean technology and energy conservation. It is suggested that a compulsory splitting up of the two regional power associations in Denmark should not be necessary. Transmission and distribution must continue to be regulated as these are natural monopolies not compatible with competition. District heating will still be a monopoly and its prices must be closely regulated to prevent soaring. The opening up of the European gas market to competition will threaten Danish energy utilities. The increasing compulsory use of natural gas in cogeneration plants to politically determined high prices is not sustainable under competitive conditions. Energy saving activities should not be affected. Energy surcharges are attractive measures on a liberalized market. The regulation of competition ought to be incorporated explicitly as a restriction in the Ministry of Energy's energy policy regulation. Energy utilities could be excluded from participation in price setting. International regulation of competition will demand a clarification of the separation of regulatory competence between the member states and the European Commission. It will also be necessary to adjust the Danish regulation of the electricity sector to the future Scandinavian system. (AB) 77 refs

  13. Approaches to state regulation of the energy sector

    International Nuclear Information System (INIS)

    Shervashidze, N.; Stojchev, D.

    1995-01-01

    Theory and practice of economical regulation by repaying coefficient and by partial co-ordinated expenses are discussed. The example of England, Ireland, Wales and US are pointed out as showing the features of both approaches being quite interesting for Bulgarian energy sector, facing the introduction of modern economical regulation. The specific character of Bulgarian energy sector is described and some conclusions are drawn concerning appropriate regulating methods. 6 refs. (orig.)

  14. Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis.

    Science.gov (United States)

    Nin, Veronica; Chini, Claudia C S; Escande, Carlos; Capellini, Verena; Chini, Eduardo N

    2014-02-28

    Liver gluconeogenesis is essential to provide energy to glycolytic tissues during fasting periods. However, aberrant up-regulation of this metabolic pathway contributes to the progression of glucose intolerance in individuals with diabetes. Phosphoenolpyruvate carboxykinase (PEPCK) expression plays a critical role in the modulation of gluconeogenesis. Several pathways contribute to the regulation of PEPCK, including the nuclear receptor Rev-erbα and the histone deacetylase SIRT1. Deleted in breast cancer 1 (DBC1) is a nuclear protein that binds to and regulates both Rev-erbα and SIRT1 and, therefore, is a candidate to participate in the regulation of PEPCK. In this work, we provide evidence that DBC1 regulates glucose metabolism and the expression of PEPCK. We show that DBC1 levels decrease early in the fasting state. Also, DBC1 KO mice display higher gluconeogenesis in a normal and a high-fat diet. DBC1 absence leads to an increase in PEPCK mRNA and protein expression. Conversely, overexpression of DBC1 results in a decrease in PEPCK mRNA and protein levels. DBC1 regulates the levels of Rev-erbα, and manipulation of Rev-erbα activity or levels prevents the effect of DBC1 on PEPCK. In addition, Rev-erbα levels decrease in the first hours of fasting. Finally, knockdown of the deacetylase SIRT1 eliminates the effect of DBC1 knockdown on Rev-erbα levels and PEPCK expression, suggesting that the mechanism of PEPCK regulation is, at least in part, dependent on the activity of this enzyme. Our results point to DBC1 as a novel regulator of gluconeogenesis.

  15. Annual report 2011 the Norwegian energy regulator

    Energy Technology Data Exchange (ETDEWEB)

    Soeiland, Arne; Lund, Per Tore

    2012-07-01

    The report provides an overview of the current regulation of the electricity and district heating markets in Norway, and explains relevant market developments. An overview of legislative amendments, research work and international participation is also presented in the report (Author)

  16. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy ( ...

  17. Energy in transition. Between regulation and market

    International Nuclear Information System (INIS)

    Horzetzky, Guenther

    2016-01-01

    Actually, the energy industry is affected in a changing market environment. The expansion of the renewables led to a share of about 30 % of the German electricity production and is always rising. The renewables energy levy has reached a level of 6.35 Euro Cents per kWh, which is actually a high level. Investments in new power plants are stopped due to low market electricity prices. The market pressure on the utilities is high and their business models have to be scrutinised. The NRW state government supports the magic political triangle of a secure, affordable and environmentally friendly energy supply. Instead of further interventions we have to develop our existing energy system cautiously. Anything else would not meet the requirements for invests in the energy supply and the magic triangle of energy politics.

  18. Classification of low energy houses in Danish Building Regulations

    DEFF Research Database (Denmark)

    Rose, Jørgen; Svendsen, Svend

    2005-01-01

    The new Danish Building Regulations (Building Regulations, 2005) introduces the total energy consumption, i.e. energy use for heating, ventilation, cooling and domestic hot water, for buildings as a measure for the energy efficiency of new buildings, i.e. moving away from the former U-value demands....... In addition to the minimum requirements for new buildings, the new Building Regulations also specify requirements for characterizing a building as either low energy building class 1 or low energy building class 2. This paper describes a type-house that is presently being built in Denmark. The type......-house easily meets the requirements for being categorized as a low energy building class 1, and the paper investigates how much U-values can be increased if the type-house were to fulfil the requirements for a low energy building class 2 or a building that just fulfils the minimum demands....

  19. Proposed general amendments to the atomic energy control regulations

    International Nuclear Information System (INIS)

    1986-01-01

    Canada's Atomic Energy Control Act defines the powers and responsibilities of the Atomic Energy Control Board (AECB). Among these is to make regulations to control the development, application and use of atomic energy. In these proposed general amendments to the Atomic Energy Control Regulations substantial changes are proposed in the designation of the authority of AECB staff, exemptions from licensing, international safeguards, duties of licensees and atomic radiation workers, security of information, and provision for hearings. The scope of the control of atomic energy has been redefined as relating to matters of health, safety, security, international safeguards, and the protection of the environment

  20. Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

    Science.gov (United States)

    Gray, Lawrence R; Sultana, Mst Rasheda; Rauckhorst, Adam J; Oonthonpan, Lalita; Tompkins, Sean C; Sharma, Arpit; Fu, Xiaorong; Miao, Ren; Pewa, Alvin D; Brown, Kathryn S; Lane, Erin E; Dohlman, Ashley; Zepeda-Orozco, Diana; Xie, Jianxin; Rutter, Jared; Norris, Andrew W; Cox, James E; Burgess, Shawn C; Potthoff, Matthew J; Taylor, Eric B

    2015-10-06

    Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Hepatic expression of proteasome subunit alpha type-6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin-like modifier, a proviral host gene in hepatitis C virus infection.

    Science.gov (United States)

    Broering, R; Trippler, M; Werner, M; Real, C I; Megger, D A; Bracht, T; Schweinsberg, V; Sitek, B; Eisenacher, M; Meyer, H E; Baba, H A; Weber, F; Hoffmann, A-C; Gerken, G; Schlaak, J F

    2016-05-01

    The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infection. Transcriptomic and proteomic analyses were performed using liver samples of HCV-infected (n = 54) and uninfected (n = 10) or HBV-infected controls (n = 23). Primary human hepatocytes (PHH) were treated with Toll-like receptor ligands, interferons and kinase inhibitors. Expression of ISG15 and proteasome subunit alpha type-6 (PSMA6) was suppressed in subgenomic HCV replicon cell lines using specific siRNAs. Comparison of hepatic expression patterns revealed significantly increased signals for ISG15, IFIT1, HNRNPK and PSMA6 on the protein level as well as ISG15, IFIT1 and PSMA6 on the mRNA level in HCV-infected patients. In contrast to interferon-stimulated genes, PSMA6 expression occurred independent of HCV load and genotype. In PHH, the expression of ISG15 and PSMA6 was distinctly induced by poly(I:C), depending on IRF3 activation or PI3K/AKT signalling, respectively. Suppression of PSMA6 in HCV replicon cells led to significant induction of ISG15 expression, thus combined knock-down of both genes abrogated the antiviral effect induced by the separate suppression of ISG15. These data indicate that hepatic expression of PSMA6, which is upregulated during viral hepatitis, likely depends on TLR3 activation. PSMA6 affects the expression of immunoregulatory ISG15, a proviral factor in the pathogenesis of HCV infection. Therefore, the proteasome might be involved in the enigmatic interaction between ISG15 and HCV. © 2016 John Wiley & Sons Ltd.

  2. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters

    Science.gov (United States)

    Wu, Minhao; Dong, Bin; Cao, Aiqin; Li, Hai; Liu, Jingwen

    2015-01-01

    Background PCSK9 has emerged as a key regulator of serum LDL-C metabolism by promoting the degradation of hepatic LDL receptor (LDLR). In this study, we investigated the effect of fasting on serum PCSK9, LDL-C, and hepatic LDLR expression in hamsters and further delineated the molecular pathways involved in fasting-induced repression of PCSK9 transcription. Results Fasting had insignificant effects on serum total cholesterol and HDL-C levels, but reduced LDL-C, triglyceride and insulin levels. The decrease in serum LDL-C was accompanied by marked reductions of hepatic PCSK9 mRNA and serum PCSK9 protein levels with concomitant increases of hepatic LDLR protein amounts. Fasting produced a profound impact on SREBP1 expression and its transactivating activity, while having modest effects on mRNA expressions of SREBP2 target genes in hamster liver. Although PPARα mRNA levels in hamster liver were elevated by fasting, ligand-induced activation of PPARα with WY14643 compound in hamster primary hepatocytes did not affect PCSK9 mRNA or protein expressions. Further investigation on HNF1α, a critical transactivator of PCSK9, revealed that fasting did not alter its mRNA expression, however, the protein abundance of HNF1α in nuclear extracts of hamster liver was markedly reduced by prolonged fasting. Conclusion Fasting lowered serum LDL-C in hamsters by increasing hepatic LDLR protein amounts via reductions of serum PCSK9 levels. Importantly, our results suggest that attenuation of SREBP1 transactivating activity owing to decreased insulin levels during fasting is primarily responsible for compromised PCSK9 gene transcription, which was further suppressed after prolonged fasting by a reduction of nuclear HNF1α protein abundance. PMID:22954675

  3. A novel role for adiponectin in regulating the immune responses in chronic hepatitis C virus infection.

    Science.gov (United States)

    Palmer, Clovis; Hampartzoumian, Taline; Lloyd, Andrew; Zekry, Amany

    2008-08-01

    Adipose tissue releases pro-inflammatory and anti-inflammatory mediators, including adiponectin, which elicit a broad range of metabolic and immunological effects. The study aim was to determine in subjects infected with chronic hepatitis C virus (HCV) the effects of total adiponectin and its high-molecular-weight (HMW) and low-molecular-weight isoforms on HCV-specific immune responses. Serum levels of total adiponectin and its isoforms were determined by immunoassay. The ex vivo effect of adiponectin on the HCV-specific T-cell response was examined by interferon gamma (IFN-gamma) enzyme-linked immunosorbent spot and enzyme-linked immunosorbent assay cytokine assays. The role of the mitogen-activated protein kinase (MAPK) signaling pathway in mediating the adiponectin effect on T cells was also evaluated. We found that serum levels of total and HMW adiponectin were significantly decreased in subjects with chronic HCV and increased body mass index (BMI) compared with HCV-infected lean subjects. The presence of an anti-HCV specific immune response was strongly associated with lower BMI (P = 0.004) and higher serum total (P = 0.01) and HMW (P = 0.02) adiponectin. In ex vivo assays, total adiponectin and the HMW adiponectin isoform enhanced HCV-specific IFN-gamma production (P = 0.02 and 0.03, respectively). Adiponectin-R1 receptors were expressed on T cells and monocytes. In depletion experiments, the IFN-gamma response to adiponectin was entirely dependent on the simultaneous presence of both CD4 and CD8 T cells, and to a lesser extent, natural killer cells. Selective inhibition of p38MAPK activity by SB203580 abrogated the IFN-gamma response to adiponectin, whereas extracellular signal-regulated kinase 1/2 inhibition by PD98059 did not affect the response. In chronic HCV, a reciprocal association exists between BMI, adiponectin, and the anti-HCV immune responses, emphasizing the important role played by adiposity in regulating the immune response in HCV infection.

  4. Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia

    Directory of Open Access Journals (Sweden)

    Fassil Shiferaw

    2016-08-01

    Full Text Available Abstract Background Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. Methods This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees’ responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful

  5. Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia.

    Science.gov (United States)

    Shiferaw, Fassil; Letebo, Mekitew; Bane, Abate

    2016-08-11

    Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees' responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful categories. The World Health Organization (WHO) global

  6. miR-217 regulates ethanol-induced hepatic inflammation by disrupting sirtuin 1-lipin-1 signaling.

    Science.gov (United States)

    Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O; You, Min

    2015-05-01

    Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and in primary Kupffer cells. In macrophages, ethanol substantially exacerbated LPS-mediated induction of miR-217 and production of proinflammatory cytokines compared with LPS or ethanol alone. Consistently, ethanol administration to mice led to increases in miR-217 abundance and increased production of inflammatory cytokines in isolated primary Kupffer cells exposed to the combination of ethanol and LPS. miR-217 promoted combined ethanol and LPS-mediated inhibition of sirtuin 1 expression and activity in macrophages. Moreover, miR-217-mediated sirtuin 1 inhibition was accompanied by increased activities of two vital inflammatory regulators, NF-κB and the nuclear factor of activated T cells c4. Finally, adenovirus-mediated overexpression of miR-217 led to steatosis and inflammation in mice. These findings suggest that miR-217 is a pivotal regulator involved in ethanol-induced hepatic inflammation. Strategies to inhibit hepatic miR-217 could be a viable approach in attenuating alcoholic hepatitis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of α-Cell Mass

    Directory of Open Access Journals (Sweden)

    Mark J. Solloway

    2015-07-01

    Full Text Available Understanding the regulation of islet cell mass has important implications for the discovery of regenerative therapies for diabetes. The liver plays a central role in metabolism and the regulation of endocrine cell number, but liver-derived factors that regulate α-cell and β-cell mass remain unidentified. We propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent control of hepatic amino acid metabolism regulates α-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced α-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent α-cell replication ex vivo and enabled conversion of α-cells into β-like cells in vivo. Serum amino acids and α-cell proliferation were increased in neonatal mice but fell throughout postnatal development in a glucagon-dependent manner. These data reveal that amino acids act as sensors of glucagon signaling and can function as growth factors that increase α-cell proliferation.

  8. Building regulations in energy efficiency: Compliance in England and Wales

    International Nuclear Information System (INIS)

    Pan Wei; Garmston, Helen

    2012-01-01

    There is an international pragmatic shift towards the use of building energy regulations, standards and codes to reduce building energy consumption. The UK Government revised Building Regulations in 2002, 2006 and 2010, towards more stringent energy efficiency standards and ultimately the target of ‘zero carbon’ new homes from 2016. This paper aims to: reveal levels of compliance with energy Building Regulations of new-build dwellings in England and Wales; explore underlying issues; and identify possible solutions. In total 376 new-build dwellings were investigated. The compliance revealed was poor, at a level of 35%; accompanied by 43% ‘grey compliance’ and 21% ‘grey non-compliance’ (due to insufficient evidence of achieving required carbon emissions reductions). It is a serious concern when building control approves so many dwellings when insufficient evidence of compliance has been received. Underlying issues were centred on: incorrect compilation and/or insufficient submission of carbon emissions calculations by builders/developers; inappropriate timings of such submissions; and a paucity of proper checks by building control. Exploring these issues reveals a complex system of factors influencing energy regulations compliance, which involves a wide range of stakeholders. The findings should inform the formulation and implementation of energy efficiency building regulations and policy in the future. - Highlights: ► The compliance with energy Building Regulations (England and Wales) was poor. ► The problematic implementation of energy Building Regulations is a serious concern. ► Identified issues suggest a lack of knowledge of builders and building control. ► There is a complex system of factors influencing energy regulations compliance. ► A systems approach is needed to improve compliance, while training is crucial.

  9. Evaluating the Value of Flexibility in Energy Regulation Markets

    DEFF Research Database (Denmark)

    Neupane, Bijay; Pedersen, Torben Bach; Thiesson, Bo

    2015-01-01

    In this paper, we perform an econometric analysis on the benefits of introducing flexibility in the Danish/Nordic regulating power market. The paper investigates the relationships between market power prices and regulation volumes, in order to quantify the effects of flexibility on regulating power...... prices. Further, we analyze the benefit for various types of flexibility and market objectives, to detect the type of energy flexibility that maximizes the benefits. Results show that if 3.87% of total demand is flexible, market can reduce the regulation cost by 49% and the regulation volume by 29.4%....

  10. Overfeeding Dairy Cattle During Late-Pregnancy Alters Hepatic PPARα-Regulated Pathways Including Hepatokines: Impact on Metabolism and Peripheral Insulin Sensitivity

    Science.gov (United States)

    Khan, M Jawad; Jacometo, Carolina B; Graugnard, Daniel E; Corrêa, Marcio N; Schmitt, Eduardo; Cardoso, Felipe; Loor, Juan J

    2014-01-01

    Hepatic metabolic gene networks were studied in dairy cattle fed control (CON, 1.34 Mcal/kg) or higher energy (overfed (OVE), 1.62 Mcal/kg) diets during the last 45 days of pregnancy. A total of 57 target genes encompassing PPARα-targets/co-regulators, hepatokines, growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis, lipogenesis, and lipoprotein metabolism were evaluated on −14, 7, 14, and 30 days around parturition. OVE versus CON cows were in more negative energy balance (NEB) postpartum and had greater serum non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and liver triacylglycerol (TAG) concentrations. Milk synthesis rate did not differ. Liver from OVE cows responded to postpartal NEB by up-regulating expression of PPARα-targets in the fatty acid oxidation and ketogenesis pathways, along with gluconeogenic genes. Hepatokines (fibroblast growth factor 21 (FGF21), angiopoietin-like 4 (ANGPTL4)) and apolipoprotein A-V (APOA5) were up-regulated postpartum to a greater extent in OVE than CON. OVE led to greater blood insulin prepartum, lower NEFA:insulin, and greater lipogenic gene expression suggesting insulin sensitivity was not impaired. A lack of change in APOB, MTTP, and PNPLA3 coupled with upregulation of PLIN2 postpartum in cows fed OVE contributed to TAG accumulation. Postpartal responses in NEFA and FGF21 with OVE support a role of this hepatokine in diminishing adipose insulin sensitivity. PMID:24737933

  11. Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yap, Chui Sun; Sinha, Rohit Anthony [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore); Ota, Sho; Katsuki, Masahito [Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Yen, Paul Michael, E-mail: paul.yen@duke-nus.edu.sg [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore)

    2013-11-01

    Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

  12. Energy Regulation Commission. Activity report. 1 July - 31 December 2008

    International Nuclear Information System (INIS)

    2009-01-01

    After a description of the scope of activities, organisation and operation of the CRE (Commission de Regulation de l'Energie, Energy regulation commission) and of the CorDIS (Comite de reglement des differents et des sanctions de la CRE, CRE's Committee for settlements of controversies and sanctions), this report outlines the importance of the grid manager independence and of the regulation reinforcement for the building up of a domestic energy market. It discusses the role of the regulation authority in the interconnection of European grids, their operation security and supply security, but also in pricing and in investments. It highlights the relationship between the reduction of carbon emission, energy demand management, strengthening of electric grids, financial incentives, and advanced metering systems. It describes how the CRE ensures a good operation of electricity and natural gas markets

  13. Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

    Directory of Open Access Journals (Sweden)

    Haji Akbar

    Full Text Available In rodents, fibroblast growth factor 21 (FGF21 has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON or receiving 50 g/d of L-carnitine (C50 from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100 resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM or lower-energy (CON; 1.34 Mcal/kg DM diet and received 0 (OVE:N, CON:N or 200 μg of LPS (OVE:Y, CON:Y into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits

  14. Alterations in Hepatic FGF21, Co-Regulated Genes, and Upstream Metabolic Genes in Response to Nutrition, Ketosis and Inflammation in Peripartal Holstein Cows.

    Science.gov (United States)

    Akbar, Haji; Batistel, Fernanda; Drackley, James K; Loor, Juan J

    2015-01-01

    In rodents, fibroblast growth factor 21 (FGF21) has emerged as a key metabolic regulator produced by liver. To gather preliminary data on the potential importance of FGF1, co-regulated genes, and upstream metabolic genes, we examined the hepatic mRNA expression in response to nutrition and inflammation in dairy cows. In experiment 1, induction of ketosis through feed restriction on d 5 postpartum upregulated FGF21, its co-receptor KLB, and PPARA but only elicited a numerical increase in serum FGF21 concentration. In experiment 2, cows in control (CON) or receiving 50 g/d of L-carnitine (C50) from -14 through 21 d had increased FGF21, PPARA, and NFIL3 on d 10 compared with d 2 postpartum. In contrast, compared with CON and C50, 100 g/d L-carnitine (C100) resulted in lower FGF21, KLB, ANGPTL4, and ARNTL expression on d 10. In experiment 3, cows were fed during the dry period either a higher-energy (OVE; 1.62 Mcal/kg DM) or lower-energy (CON; 1.34 Mcal/kg DM) diet and received 0 (OVE:N, CON:N) or 200 μg of LPS (OVE:Y, CON:Y) into the mammary gland at d 7 postpartum. For FGF21 mRNA expression in CON, the LPS challenge (CON:Y) prevented a decrease in expression between d 7 and 14 postpartum such that cows in CON:N had a 4-fold lower expression on d 14 compared with d 7. The inflammatory stimulus induced by LPS in CON:Y resulted in upregulation of PPARA on d 14 to a similar level as cows in OVE:N. In OVE:Y, expression of PPARA was lower than CON:N on d 7 and remained unchanged on d 14. On d 7, LPS led to a 4-fold greater serum FGF21 only in OVE but not in CON cows. In fact, OVE:Y reached the same serum FGF21 concentration as CON:N, suggesting a carryover effect of dietary energy level on signaling mechanisms within liver. Overall, results indicate that nutrition, ketosis, and inflammation during the peripartal period can alter hepatic FGF21, co-regulated genes, and upstream metabolic genes to various extents. The functional outcome of these changes merits further study

  15. Public opinion poll on safety and regulations of nuclear energy

    Energy Technology Data Exchange (ETDEWEB)

    Park, M. I.; Park, B. I.; Lee, S. M. [Gallup Korea, Seoul (Korea, Republic of)

    2004-02-15

    The purpose of this poll is not only to research understanding on safety and regulations of nuclear energy and to compare the result by time series followed 2003 to 2002 years, also to establish the public relations strategies and to offer information for developing long-term policies. The contents of the study are on the general perception, safety, management of nuclear power station, regulations and surroundings about nuclear energy.

  16. Exosome RNA Released by Hepatocytes Regulates Innate Immune Responses to Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Takahisa Kouwaki

    2016-08-01

    Full Text Available The innate immune system is essential for controlling viral infection. Hepatitis B virus (HBV persistently infects human hepatocytes and causes hepatocellular carcinoma. However, the innate immune response to HBV infection in vivo remains unclear. Using a tree shrew animal model, we showed that HBV infection induced hepatic interferon (IFN-γ expression during early infection. Our in vitro study demonstrated that hepatic NK cells produced IFN-γ in response to HBV only in the presence of hepatic F4/80+ cells. Moreover, extracellular vesicles released from HBV-infected hepatocytes contained viral nucleic acids and induced NKG2D ligand expression in macrophages by stimulating MyD88, TICAM-1, and MAVS-dependent pathways. In addition, depletion of exosomes from extracellular vesicles markedly reduced NKG2D ligand expression, suggesting the importance of exosomes for NK cell activation. In contrast, infection of hepatocytes with HBV increased immunoregulatory microRNA levels in extracellular vesicles and exosomes, which were transferred to macrophages, thereby suppressing IL-12p35 mRNA expression in macrophages to counteract the host innate immune response. IFN-γ increased the hepatic expression of DDX60 and augmented the DDX60-dependent degradation of cytoplasmic HBV RNA. Our results elucidated the crucial role of exosomes in antiviral innate immune response against HBV.

  17. Exposure to a northern contaminant mixture (NCM alters hepatic energy and lipid metabolism exacerbating hepatic steatosis in obese JCR rats.

    Directory of Open Access Journals (Sweden)

    Ryan J Mailloux

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to 10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with

  18. EU Energy Market and Regulation enter a new Framework: Energy Union

    International Nuclear Information System (INIS)

    Sencar, M.

    2015-01-01

    Energy Union provides a new framework for market and regulation. This contribution discusses its main elements (dimensions), in particular energy market functioning. Energy Union adds some new focal points to its development, e.g. research and innovation, in addition to sustainability. Energy Union also aims at improving customers position on the market, and paves the way for efficiency enhancements in regulation and market monitoring at European level. Three aspects of potential future improvements are discussed how the existing Agency for the Cooperation of Energy Regulators may further contribute to the efficient market functioning and implementation of planned infrastructure investment. (author).

  19. Dietary fatty acids regulate hepatic low density lipoprotein (LDL) transport by altering LDL receptor protein and mRNA levels.

    Science.gov (United States)

    Horton, J D; Cuthbert, J A; Spady, D K

    1993-01-01

    The concentration of LDL in plasma is strongly influenced by the amount and the type of lipid in the diet. Recent studies in the hamster have shown that dietary fatty acids differentially affect circulating LDL levels primarily by altering receptor-dependent LDL uptake in the liver. To investigate the mechanistic basis of this effect, rates of receptor-dependent LDL transport in the liver were correlated with LDL receptor protein and mRNA levels in hamsters fed safflower oil or coconut oil and varying amounts of cholesterol. Hepatic LDL receptor activity was significantly lower in animals fed coconut oil than in animals fed safflower oil at all levels of cholesterol intake (26, 53, and 61% lower at cholesterol intakes of 0, 0.06, and 0.12%, respectively). These fatty acid-induced changes in hepatic LDL receptor activity were accompanied by parallel changes in hepatic LDL receptor protein and mRNA levels, suggesting that dietary fatty acids regulate the LDL receptor pathway largely at the mRNA level. Images PMID:8349814

  20. TRIF Differentially Regulates Hepatic Steatosis and Inflammation/Fibrosis in MiceSummary

    Directory of Open Access Journals (Sweden)

    Ling Yang

    2017-05-01

    Full Text Available Background & Aims: Toll-like receptor 4 (TLR4 signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF. TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steatosis and inflammation/fibrosis. Methods: A choline-deficient amino acid defined (CDAA diet was used for the mouse NASH model. On this diet, the mice develop hepatic steatosis, inflammation, and fibrosis. TLR4 wild-type and TLR4-/- bone marrow chimeric mice and TRIF-/- mice were fed CDAA or a control diet for 22 weeks. Hepatic steatosis, inflammation, and fibrosis were examined. Results: In the CDAA diet–induced NASH, the mice with wild-type bone marrow had higher alanine aminotransferase and hepatic tumor necrosis factor levels than the mice with TLR4-/- bone marrow. The nonalcoholic fatty liver disease activity score showed that both wild-type and TLR4-/- bone marrow chimeras had reduced hepatic steatosis, and that both types of chimeras had similar levels of inflammation and hepatocyte ballooning to whole-body wild-type mice. Notably, wild-type recipients showed more liver fibrosis than TLR4-/- recipients. Although TRIF-/- mice showed reduced hepatic steatosis, these mice showed more liver injury, inflammation, and fibrosis than wild-type mice. TRIF-/- stellate cells and hepatocytes produced more C-X-C motif chemokine ligand 1 (CXCL1 and C-C motif chemokine ligand than wild-type cells in response to lipopolysaccharide. Consistently, TRIF-/- mice showed increased CXCL1 and CCL3 expression along with neutrophil and macrophage infiltration, which promotes liver inflammation and injury. Conclusions: In TLR4-mediated NASH, different liver cells have distinct roles in hepatic steatosis, inflammation, and fibrosis. TRIF promotes hepatic

  1. Hepatic deficiency of the pioneer transcription factor FoxA restricts hepatitis B virus biosynthesis by the developmental regulation of viral DNA methylation.

    Directory of Open Access Journals (Sweden)

    Vanessa C McFadden

    2017-02-01

    Full Text Available The FoxA family of pioneer transcription factors regulates hepatitis B virus (HBV transcription, and hence viral replication. Hepatocyte-specific FoxA-deficiency in the HBV transgenic mouse model of chronic infection prevents the transcription of the viral DNA genome as a result of the failure of the developmentally controlled conversion of 5-methylcytosine residues to cytosine during postnatal hepatic maturation. These observations suggest that pioneer transcription factors such as FoxA, which mark genes for expression at subsequent developmental steps in the cellular differentiation program, mediate their effects by reversing the DNA methylation status of their target genes to permit their ensuing expression when the appropriate tissue-specific transcription factor combinations arise during development. Furthermore, as the FoxA-deficient HBV transgenic mice are viable, the specific developmental timing, abundance and isoform type of pioneer factor expression must permit all essential liver gene expression to occur at a level sufficient to support adequate liver function. This implies that pioneer transcription factors can recognize and mark their target genes in distinct developmental manners dependent upon, at least in part, the concentration and affinity of FoxA for its binding sites within enhancer and promoter regulatory sequence elements. This selective marking of cellular genes for expression by the FoxA pioneer factor compared to HBV may offer the opportunity for the specific silencing of HBV gene expression and hence the resolution of chronic HBV infections which are responsible for approximately one million deaths worldwide annually due to liver cirrhosis and hepatocellular carcinoma.

  2. Stable Human Hepatoma Cell Lines for Efficient Regulated Expression of Nucleoside/Nucleotide Analog Resistant and Vaccine Escape Hepatitis B Virus Variants and Woolly Monkey Hepatitis B Virus.

    Directory of Open Access Journals (Sweden)

    Xin Cheng

    Full Text Available Hepatitis B virus (HBV causes acute and chronic hepatitis B (CHB. Due to its error-prone replication via reverse transcription, HBV can rapidly evolve variants that escape vaccination and/or become resistant to CHB treatment with nucleoside/nucleotide analogs (NAs. This is particularly problematic for the first generation NAs lamivudine and adefovir. Though now superseded by more potent NAs, both are still widely used. Furthermore, resistance against the older NAs can contribute to cross-resistance against more advanced NAs. For lack of feasible HBV infection systems, the biology of such variants is not well understood. From the recent discovery of Na+-taurocholate cotransporting polypeptide (NTCP as an HBV receptor new in vitro infection systems are emerging, yet access to the required large amounts of virions, in particular variants, remains a limiting factor. Stably HBV producing cell lines address both issues by allowing to study intracellular viral replication and as a permanent source of defined virions. Accordingly, we generated a panel of new tetracycline regulated TetOFF HepG2 hepatoma cell lines which produce six lamivudine and adefovir resistance-associated and two vaccine escape variants of HBV as well as the model virus woolly monkey HBV (WMHBV. The cell line-borne viruses reproduced the expected NA resistance profiles and all were equally sensitive against a non-NA drug. The new cell lines should be valuable to investigate under standardized conditions HBV resistance and cross-resistance. With titers of secreted virions reaching >3 x 10(7 viral genome equivalents per ml they should also facilitate exploitation of the new in vitro infection systems.

  3. Security of supply and regulation of energy networks

    International Nuclear Information System (INIS)

    Jamasb, Tooraj; Pollitt, Michael

    2008-01-01

    In recent years, the security of energy supplies has re-emerged as a central issue in the energy policy arena in the UK and elsewhere. This re-emergence takes place against a backdrop of increased liberalisation of the energy markets, so that security of supply needs to be revisited within this context. Security of supply is multifaceted, but is often discussed in terms of physical availability of energy sources and their commodity price risk. This paper discusses the relationship between security of supply and network regulation - that is, how the energy networks, and appropriate regulation of them, can contribute to security of supply in liberalised energy sectors. Energy networks are predominantly natural monopolies and as a result are generally subject to regulatory oversight. We discuss a range of issues and trends that pose challenges and opportunities to network regulation and which call for new and innovative measures. The paper identifies a number of areas where network regulation can play a significant role in increasing the security of supply of future energy systems. (author)

  4. Regulation proposal for voluntary energy efficiency labelling of commercial buildings

    International Nuclear Information System (INIS)

    Lamberts, Roberto; Goulart, Solange; Carlo, Joyce; Westphal, Fernando

    2006-01-01

    Despite of Brazil not being between the major world energy consumers, the consumption of electricity has significantly increased in the late years. The National Energy Balance of 2005, published by the Brazilian Ministry of Energy, showed an increasing of the participation of electricity in the final energy consumption of 15.7% in 2002 to 16.2% in 2004. Initially, a brief review of the initiatives taken by Brazilian Government aiming to limit and control the energy consumption in buildings is presented. Then, the regulation proposal containing the technical requirements to classify the energy efficiency level of buildings is shown. The purpose of this voluntary regulation is to provide conditions to certify the energy efficiency level of Brazilian buildings (commercial and public). It specifies the methods for energy efficiency rating of buildings and includes requirements to attend energy conservation measures in three main issues: lighting system; air conditioning system and envelope. The regulation applies to large buildings (minimum total area of 500 m 2 or when the energy demand is greater than or equal to 2,3 kV, including: Conditioned buildings; Partially conditioned buildings and Naturally ventilated buildings. (author)

  5. The Europeanization of regulation of the energy sector

    International Nuclear Information System (INIS)

    Lavrijsen, S.A.C.M.; Nauta, T.

    2010-01-01

    The main question of this article is how the ongoing Europeanization of regulation relates to the restrictive manner in which the Dutch legislator interprets the principle of legality with respect to the qualification of the independent regulating authorities. To answer this question, research focuses first of all on which demands are imposed by European law on the constitutional position and qualification of the national regulating authorities that implement the energy directives. Anticipating the consequences of the third generation of energy directives for the position of the national authorities, attention is subsequently paid to the question whether any tension exists between European requirements for the regulation of the energy sector and the manner in which the national legislator interprets the principle of legality. [nl

  6. Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression.

    Science.gov (United States)

    Eraky, Salma M; El-Mesery, Mohamed; El-Karef, Amro; Eissa, Laila A; El-Gayar, Amal M

    2018-05-01

    Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  7. Energy policy conference on the regulation of energy industries; Conference de politique energetique sur la regulation des industries energetiques

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-11-01

    This document is the report of the conference meeting jointly organized by the French general plan commission and the general direction of energy and raw materials on the regulation of energy industries: 1 - the changes in the regulation of public utilities in competition: harmonization, respect of impartiality and social cohesion, organization of a loyal competition, specialized regulation and regulation of competition, open debates; 2 - towards an homogenous model of regulatory authority?: the US model (collegial and hybrid organizations), the UK model (individual and independent), missions of regulation and institutional 'meccano', theory and practice, draft classification of the institutional approaches of IEA countries (role of ministries and regulatory agencies), independent regulatory authorities or not, significant differences in converging models, dominant types of regulation in the different sectors, situation of the French energy regulatory system (institutional plan, regulation processes, relations of the regulation authority with the government), reasons of the differences between different countries, expected evolution of the regulation systems in the coming years. (J.S.)

  8. Energy policy conference on the regulation of energy industries; Conference de politique energetique sur la regulation des industries energetiques

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-11-01

    This document is the report of the conference meeting jointly organized by the French general plan commission and the general direction of energy and raw materials on the regulation of energy industries: 1 - the changes in the regulation of public utilities in competition: harmonization, respect of impartiality and social cohesion, organization of a loyal competition, specialized regulation and regulation of competition, open debates; 2 - towards an homogenous model of regulatory authority?: the US model (collegial and hybrid organizations), the UK model (individual and independent), missions of regulation and institutional 'meccano', theory and practice, draft classification of the institutional approaches of IEA countries (role of ministries and regulatory agencies), independent regulatory authorities or not, significant differences in converging models, dominant types of regulation in the different sectors, situation of the French energy regulatory system (institutional plan, regulation processes, relations of the regulation authority with the government), reasons of the differences between different countries, expected evolution of the regulation systems in the coming years. (J.S.)

  9. Novel Molecules Regulating Energy Homeostasis: Physiology and Regulation by Macronutrient Intake and Weight Loss

    Directory of Open Access Journals (Sweden)

    Anna Gavrieli

    2016-09-01

    Full Text Available Excess energy intake, without a compensatory increase of energy expenditure, leads to obesity. Several molecules are involved in energy homeostasis regulation and new ones are being discovered constantly. Appetite regulating hormones such as ghrelin, peptide tyrosine-tyrosine and amylin or incretins such as the gastric inhibitory polypeptide have been studied extensively while other molecules such as fibroblast growth factor 21, chemerin, irisin, secreted frizzle-related protein-4, total bile acids, and heme oxygenase-1 have been linked to energy homeostasis regulation more recently and the specific role of each one of them has not been fully elucidated. This mini review focuses on the above mentioned molecules and discusses them in relation to their regulation by the macronutrient composition of the diet as well as diet-induced weight loss.

  10. Hepatic Aryl hydrocarbon Receptor Nuclear Translocator (ARNT regulates metabolism in mice.

    Directory of Open Access Journals (Sweden)

    Christopher H Scott

    Full Text Available Aryl hydrocarbon Receptor Nuclear Translocator (ARNT and its partners hypoxia-inducible factors (HIF-1α and HIF-2α are candidate factors for the well-known link between the liver, metabolic dysfunction and elevation in circulating lipids and glucose. Methods: Hepatocyte-specific ARNT-null (LARNT, HIF-1α-null (LHIF1α and HIF-2α-null (LHIF2α mice were created.LARNT mice had increased fasting glucose, impaired glucose tolerance, increased glucose production, raised post-prandial serum triglycerides (TG and markedly lower hepatic ATP versus littermate controls. There was increased expression of G6Pase, Chrebp, Fas and Scd-1 mRNAs in LARNT animals. Surprisingly, LHIF1α and LHIF2α mice exhibited no alterations in any metabolic parameter assessed.These results provide convincing evidence that reduced hepatic ARNT can contribute to inappropriate hepatic glucose production and post-prandial dyslipidaemia. Hepatic ARNT may be a novel therapeutic target for improving post-prandial hypertriglyceridemia and glucose homeostasis.

  11. DYRK1A is a regulator of S phase entry in hepatic progenitor cells

    NARCIS (Netherlands)

    Kruitwagen, Hedwig Suzanne; Westendorp, Bart; Viebahn, Cornelia S; Post, Krista; van Wolferen, Monique E; Oosterhoff, Loes A; Egan, David A; Delabar, Jean-Maurice; Toussaint, Mathilda Jm; Schotanus, Baukje A; de Bruin, Alain; Rothuizen, Jan; Penning, Louis C; Spee, Bart

    Hepatic progenitor cells (HPCs) are adult liver stem cells that act as second line of defense in liver regeneration. They are normally quiescent, but in case of severe liver damage HPC proliferation is triggered by external activation mechanisms from their niche. Although several important

  12. (-) Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high fat diet

    Science.gov (United States)

    (-)-Epicatechin (EC) is a natural flavanol monomer found in cocoa, green tea and a variety of other plant foods. Recent studies have shown that EC and foods rich in EC exerted vascular protective effects. In this study, effects of EC on blood lipids and hepatic steatosis, and the underlying mechani...

  13. PPARα Is Required for PPARδ Action in Regulation of Body Weight and Hepatic Steatosis in Mice

    Directory of Open Access Journals (Sweden)

    Wojciech G. Garbacz

    2015-01-01

    Full Text Available Peroxisome proliferator activated receptors alpha (PPARα and delta (PPARδ belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.

  14. PGC-1α in the exercise training-mediated regulation of hepatic UPR in mice

    DEFF Research Database (Denmark)

    Maag Kristensen, Caroline

    not be elucidated, because exercise training only had minor effects in the control mice. Study II demonstrated that aging mice had elevated hepatic triglyceride content, a tendency for increased BiP protein, decreased PERK protein content as well as increased IRE1α and cleaved ATF6 protein level in the liver...

  15. Compliance with building energy regulations for new-build dwellings

    International Nuclear Information System (INIS)

    Pan, Wei; Garmston, Helen

    2012-01-01

    Despite increasingly stringent building energy regulations worldwide, non-compliance exists in practice. This paper examines the profile of compliance with building energy regulations for new-build dwellings. In total 404 new-build dwellings completed in the UK from 2006 to 2009 were investigated. Only a third of these dwellings were evidenced as being compliant with Building Regulations Part L (England and Wales). Such low compliance casts a serious concern over the achievability of the UK Government's target for all new-build homes to be ‘zero carbon’ from 2016. Clearly evidenced was a lack of knowledge of Part L and its compliance requirements among the supply and building control sides of new-build dwellings. The results also indicate that the compliance profile was influenced by factors including Standard Assessment Procedure (UK Government's methodology for energy efficiency) calculation submissions, learning and experience of builders and building controls with Part L, use of Part L1A checklist, the introduction of energy performance certificate (EPC), build method, dwelling type, and project size. Better compliance was associated with flats over houses and timber frame over masonry. The use of EPC and Part L1A checklist should be encouraged. Key to addressing the lack of compliance with building energy regulations is training. -- Highlights: ► There exists a lack of compliance, worldwide, with building energy regulations. ► The implementation of England and Wales building energy regulations is problematic. ► Training, learning and experience of builders and building control are critical. ► Energy performance certificate and Part L 2006 checklist helped achieve compliance. ► Flats achieved better compliance over houses; and timber frame over masonry.

  16. Hepatitis C virus core protein regulates p300/CBP co-activation function. Possible role in the regulation of NF-AT1 transcriptional activity

    International Nuclear Information System (INIS)

    Gomez-Gonzalo, Marta; Benedicto, Ignacio; Carretero, Marta; Lara-Pezzi, Enrique; Maldonado-Rodriguez, Alejandra; Moreno-Otero, Ricardo; Lai, Michael M.C.; Lopez-Cabrera, Manuel

    2004-01-01

    Hepatitis C virus (HCV) core is a viral structural protein; it also participates in some cellular processes, including transcriptional regulation. However, the mechanisms of core-mediated transcriptional regulation remain poorly understood. Oncogenic virus proteins often target p300/CBP, a known co-activator of a wide variety of transcription factors, to regulate the expression of cellular and viral genes. Here we demonstrate, for the first time, that HCV core protein interacts with p300/CBP and enhances both its acetyl-transferase and transcriptional activities. In addition, we demonstrate that nuclear core protein activates the NH 2 -terminal transcription activation domain (TAD) of NF-AT1 in a p300/CBP-dependent manner. We propose a model in which core protein regulates the co-activation function of p300/CBP and activates NF-AT1, and probably other p300/CBP-regulated transcription factors, by a novel mechanism involving the regulation of the acetylation state of histones and/or components of the transcriptional machinery

  17. The role of PTEN in regulation of hepatic macrophages activation and function in progression and reversal of liver fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yahui; Tian, Yuanyao; Xia, Jialu; Wu, Xiaoqin; Yang, Yang; Li, Xiaofeng; Huang, Cheng; Meng, Xiaoming; Ma, Taotao; Li, Jun, E-mail: lj@ahmu.edu.cn

    2017-02-15

    Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl{sub 4}-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl{sub 4}-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantly decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis. - Highlights: • CCl{sub 4} treatment triggered a mixed M1/M2 macrophage phenotype in fibrosis. • Lower expression of PTEN in murine M2 macrophages in vivo and vitro. • PTEN modulates M2 macrophages activation via PI3K/Akt/STAT6 signaling. • Provide a new cellular target modulate macrophage mediated hepatic fibrosis.

  18. Commission of energy regulation. 2004 activity report; Commission de regulation de l'energie. Rapport d'activite 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  19. Natural Regulation of Energy Flow in a Green Quantum Photocell.

    Science.gov (United States)

    Arp, Trevor B; Barlas, Yafis; Aji, Vivek; Gabor, Nathaniel M

    2016-12-14

    Manipulating the flow of energy in nanoscale and molecular photonic devices is of both fundamental interest and central importance for applications in light energy harvesting optoelectronics. Under erratic solar irradiance conditions, unregulated power fluctuations in a light-harvesting photocell lead to inefficient energy storage in conventional solar cells and potentially fatal oxidative damage in photosynthesis. Here, we compare the theoretical minimum energy fluctuations in nanoscale quantum heat engine photocells that incorporate one or two photon-absorbing channels and show that fluctuations are naturally suppressed in the two-channel photocell. This intrinsic suppression acts as a passive regulation mechanism that enables the efficient conversion of varying incident solar power into a steady output for absorption over a broad range of the solar spectrum on Earth. Remarkably, absorption in the green portion of the spectrum provides no inherent regulatory benefit, indicating that green light should be rejected in a photocell whose primary role is the regulation of energy flow.

  20. The Dual Role of Nrf2 in Nonalcoholic Fatty Liver Disease: Regulation of Antioxidant Defenses and Hepatic Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Sílvia S. Chambel

    2015-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a progressive liver disease with ever-growing incidence in the industrialized world. It starts with the simple accumulation of lipids in the hepatocyte and can progress to the more severe nonalcoholic steatohepatitis (NASH, which is associated with inflammation, fibrosis, and cirrhosis. There is increasing awareness that reactive oxygen species and electrophiles are implicated in the pathogenesis of NASH. Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2 is a positive regulator of the expression of a battery of genes involved in the protection against oxidative/electrophilic stress. In rodents, Nrf2 is also known to participate in hepatic fatty acid metabolism, as a negative regulator of genes that promote hepatosteatosis. We review relevant evidence in the literature that these two mechanisms may contribute to the protective role of Nrf2 in the development of hepatic steatosis and in the progression to steatohepatitis, particularly in young animals. We propose that age may be a key to explain contradictory findings in the literature. In summary, Nrf2 mediates the crosstalk between lipid metabolism and antioxidant defense mechanisms in experimental models of NAFLD, and the nutritional or pharmacological induction of Nrf2 represents a promising potential new strategy for its prevention and treatment.

  1. Scavenger receptor class B member 1 protein: hepatic regulation and its effects on lipids, reverse cholesterol transport, and atherosclerosis

    Directory of Open Access Journals (Sweden)

    Kent AP

    2011-04-01

    Full Text Available Anthony P Kent, Ioannis M StylianouDepartment of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Scavenger receptor class B member 1 (SR-BI, also known as SCARB1 is the primary receptor for the selective uptake of cholesterol from high-density lipoprotein (HDL. SR-BI is present in several key tissues; however, its presence and function in the liver is deemed the most relevant for protection against atherosclerosis. Cholesterol is transferred from HDL via SR-BI to the liver, which ultimately results in the excretion of cholesterol via bile and feces in what is known as the reverse cholesterol transport pathway. Much of our knowledge of SR-BI hepatic function and regulation is derived from mouse models and in vitro characterization. Multiple independent regulatory mechanisms of SR-BI have been discovered that operate at the transcriptional and post-transcriptional levels. In this review we summarize the critical discoveries relating to hepatic SR-BI cholesterol metabolism, atherosclerosis, and regulation of SR-BI, as well as alternative functions that may indirectly affect atherosclerosis.Keywords: SR-BI, SCARB1, lipids, atherosclerosis, CAD, mouse models

  2. Environmental regulation and the export dynamics of energy technologies

    International Nuclear Information System (INIS)

    Costantini, Valeria; Crespi, Francesco

    2008-01-01

    The pollution haven hypothesis affirms that an open market regime will encourage the flow of low-technology polluting industries towards developing countries because of potential comparative advantages related to low environmental standards. In contrast, the hypothesis suggested by Porter and van der Linde claims that innovating firms operate in a dynamic competitive situation which allows global diffusion of environmental-friendly technologies. Environmental regulation may represent a relevant mechanism through which technological change is induced. In this way, countries that are subject to more stringent environmental regulations may become net exporters of environmental technologies. This paper provides new evidence on the evolution of export flows of environmental technologies across different countries for the energy sector. Advanced economies, particularly the European Union, have increasingly focused on the role of energy policies as tools for sustaining the development path. The Kyoto Protocol commitments, together with growing import dependence on energy products, have brought attention to the analysis of innovation processes in this specific sector. The analysis uses a gravity model in order to test the determinants and the transmission channels through which environmental technologies for renewable energies and energy efficiency are exported to advanced and developing countries. Our results are consistent with the Porter and van der Linde hypothesis where environmental regulation represents a significant source of comparative advantages. What strongly emerges is that the stringency of environmental regulation supplemented by the strength of the National Innovation System is a crucial driver of export performance in the field of energy technologies. (author)

  3. CRTC2 Is a Coactivator of GR and Couples GR and CREB in the Regulation of Hepatic Gluconeogenesis.

    Science.gov (United States)

    Hill, Micah J; Suzuki, Shigeru; Segars, James H; Kino, Tomoshige

    2016-01-01

    Glucocorticoid hormones play essential roles in the regulation of gluconeogenesis in the liver, an adaptive response that is required for the maintenance of circulating glucose levels during fasting. Glucocorticoids do this by cooperating with glucagon, which is secreted from pancreatic islets to activate the cAMP-signaling pathway in hepatocytes. The cAMP-response element-binding protein (CREB)-regulated transcription coactivator 2 (CRTC2) is a coactivator known to be specific to CREB and plays a central role in the glucagon-mediated activation of gluconeogenesis in the early phase of fasting. We show here that CRTC2 also functions as a coactivator for the glucocorticoid receptor (GR). CRTC2 strongly enhances GR-induced transcriptional activity of glucocorticoid-responsive genes. CRTC2 physically interacts with the ligand-binding domain of the GR through a region spanning amino acids 561-693. Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB. CRTC2 is required for the maintenance of blood glucose levels during fasting in mice by enhancing the GR transcriptional activity on both the G6p and phosphoenolpyruvate carboxykinase (Pepck) genes. Finally, CRTC2 modulates the transcriptional activity of the progesterone receptor, indicating that it may influence the transcriptional activity of other steroid/nuclear receptors. Taken together, these results reveal that CRTC2 plays an essential role in the regulation of hepatic gluconeogenesis through coordinated regulation of the glucocorticoid/GR- and glucagon/CREB-signaling pathways on the key genes G6P and PEPCK.

  4. The commission of energy regulation: statute, missions and authority

    International Nuclear Information System (INIS)

    Laffaille, D.; Bossoutrot, Ch.

    2008-01-01

    The commission of energy regulation (CRE), which has superseded the commission of electricity regulation, was created by the law no. 2000-108 from February 10, 2000, relative to the modernization and development of the French electric utility. This article presents the situation of CRE's statute, missions and authority seven years after its creation. The statute of CRE warrants its independence, autonomy and impartiality. Its operation means consist in budgetary and personnel resources. Its main mission is the control of the conditions of use of gas and electricity networks and the respect of competition rules: free and transparent access to networks and infrastructures, control of the good operation and development of networks and facilities, regulation of markets, strengthening of the public utility mission. Its authority concerns the management of networks, the book-keeping control of energy operators, the settlement of disputes, the attribution of sanctions, the monitoring of energy markets operation etc. (J.S.)

  5. Moving from self-regulation to external regulation of Department of Energy facilities

    International Nuclear Information System (INIS)

    Wishau, R.J.; Dawson, J.; Lee, D.W.

    1999-01-01

    This paper discusses the initiative to transfer the regulation of Department of Energy (DOE) nuclear facilities to the US Nuclear Regulatory Commission (NRC). The paper gives an overview of some of the major technical, policy and legal issues that accompany this initiative. The paper focuses on specific issues and how they may be affected by external regulation of occupational radiation protection at DOE facilities. Differences between the NRC and the DOE approach to regulating nuclear safety are compared and contrasted. Some projected impacts from this transition are examined. Finally, recommendations are provided that may enhance the transition, increasing the likelihood of successful external NRC regulation

  6. Proceedings of the 11th forum: Croatian Energy Day: Regulation problems relating to energy service markets

    International Nuclear Information System (INIS)

    2002-01-01

    The main goals of the majority of processes and developments relating to energy sectors of today present the enhancement of energy sector efficiency, ensuring of stable financial sources and safe return of the means invested through practice of activities at the market of energy and energy services, i.e. public services or monopoly. This is to be achieved by means of energy sector restructuring and liberalisation, pluralism of ownership and transparency of the organisational and management scheme. Thereby, an important role and significance for the realisation of these aims, for the development and energy market functioning on the national level, as well as for the achievement of reciprocity and complementarity of national markets with regional and multi-national energy markets, is held by models and forms of energy activity regulation. In a limited sense, the regulation itself should constitute an adequate stimulating framework for free energy flows, transparent and non- discriminating conditions for the utilisation of transmission and transportation systems and networks, protection of supplier choice rights, pluralism of ownership and ownership rights, protection of energy and energy services' quality, environmental protection, protection of purchasers and consumers and protection of energy subjects. For all these reasons, aspects and problems appertaining to energy sector and energy activities' regulation have been chosen as the theme and contents of the 11th Forum. Various countries have undertaken and implemented or are in the process of implementation of different models and contents referring to energy sector and energy activity regulation. Experience and legislative practice are quoted as the main criteria. The aim of this Forum is to set forth and clarify experiences and solutions connected to the regulation of energy activities in numerous European countries or in the world

  7. Saponin Inhibits Hepatitis C Virus Propagation by Up-regulating Suppressor of Cytokine Signaling 2

    OpenAIRE

    Lee, Jihye; Lim, Seri; Kang, Sang-Min; Min, Saehong; Son, Kidong; Lee, Han Sol; Park, Eun Mee; Ngo, Huong T. T.; Tran, Huong T. L.; Lim, Yun-Sook; Hwang, Soon B.

    2012-01-01

    Saponins are a group of naturally occurring plant glycosides which possess a wide range of pharmacological properties, including anti-tumorigenic and antiviral activities. To investigate whether saponin has anti-hepatitis C virus (HCV) activity, we examined the effect of saponin on HCV replication. HCV replication was efficiently inhibited at a concentration of 10 µg/ml of saponin in cell culture grown HCV (HCVcc)-infected cells. Inhibitory effect of saponin on HCV replication was verified by...

  8. Final report of the Steering Group Regulating Energy Levies

    International Nuclear Information System (INIS)

    Wolfson, D.J.; Frijns, J.M.G.; Opschoor, J.B.; Rissik, S.A.; Stevens, L.G.M.

    1992-02-01

    The aim is to determine to what extent regulating energy levies can generate energy savings, and to gain insight into the economic impacts of energy levies. Special attention is paid to the consequences for the competitive position and the development of economic and industrial activities, employment, distribution of incomes and purchasing power. An indication is given to what extent policy tools for regulating energy levies meet the criteria for efficiency, effectivity and legitimacy. Three hypothetic measures to map the energy saving effects and economic side-effects are discussed for two tax-levels: 50% and 100%. Variant A is a fixed levy on all the primary energy carriers, implemented on an OECD-level, equally based on the carbon content and the energy content. Variant B is the same as variant A, but only implemented in the Netherlands. Variant C is a fixed levy on the energy consumption of small energy consumers in the Netherlands, which variant spares and protects the energy-intensive industry. In the chapters 5, 6 and 7 the results of preliminary studies on price elasticities and energy consumption in the road traffic sector, households, and housing construction are discussed, as well as energy conservation in the rental sector and the Dutch production economies, and the competitive impacts of energy levies on industry and business in the Netherlands. In chapter 8 and 9 possibilities to reimburse the revenues to the government, the businesses or industries, and the households, are mentioned and considered. Attention is paid to the financial consequences and the impacts on spending power. In chapter (10) the economic effects of the levy variants, as calculated by the Centraal Plan Bureau (CPB, Dutch government institute for economic planning), are described. Variant A will result in substantial negative economic effects: loss of income and a limited growth of employment, caused by transfer of part of the energy-intensive industry to outside the OECD

  9. Hepatitis C virus core protein induces dysfunction of liver sinusoidal endothelial cell by down-regulation of silent information regulator 1.

    Science.gov (United States)

    Sun, Li-Jie; Yu, Jian-Wu; Shi, Yu-Guang; Zhang, Xiao-Yu; Shu, Meng-Ni; Chen, Mo-Yang

    2018-05-01

    Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV) infection. Some evidence has suggested the potential role of silent information regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate the effect of HCV core protein on expression of SIRT1 of liver sinusoidal endothelial cell (LSEC) and function of LSEC. LSECs were co-cultured with HepG2 cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were used as controls. After co-culture, the activity and expression levels of mRNA and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit, real time-PCR (RT-PCR), Western blot, respectively. The levels of adiponectin receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by Western blot. Cluster of differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was performed by flow cytometry. The level of reactive oxygen species (ROS) was assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric oxide (NO), and endothelin-1 (ET-1) levels in the co-culture supernatant were measured. The co-culture supernatant was then used to cultivate LX-2 cells. The levels of α-smooth muscle actin (ASMA) and transforming growth factor-β1 (TGF-β1) protein in LX-2 cells were measured by Western blot. Compared with LSEC co-cultured with HepG2 cells group, in LSEC co-cultured with HepG2-core cells group, the activity and expression level of mRNA and protein of SIRT1 reduced; the level of adiponectin reduced and the expression level of AdipoR2 protein decreased; ROS levels increased; the expression level of eNOS, VEGF protein decreased; and the expression level of CD14 decreased; the expression level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET-1 and MDA levels increased; the levels of ASMA and TGF-β1 protein in LX-2 cells increased. SIRT1 activator improved the above-mentioned changes

  10. The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

    International Nuclear Information System (INIS)

    Kim, M.J.C.

    1988-01-01

    The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T 4 levels and T 4 treatment increased serum T 3 levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T 4 , the transition temperature disappeared due to a decoupling of succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T 4 treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca ++ Mg ++ ATPase and Mg ++ ATPase. T 4 treatment had potentiated this effect. T 4 increased the malate-aspartate shuttle and α-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-[ 14 C-U]/[6- 3 H]-glucose and gluconeogeneis from L-[ 14 C-U]-alanine was examined. Dietary fat or T 4 did not affect the glucose mass. T 4 increased the irreversible fractional glucose turnover rate

  11. Hepatitis C

    Science.gov (United States)

    ... Workshops Follow Us Home Health Information Liver Disease Hepatitis (Viral) Hepatitis C Related Topics English English Español Section Navigation Hepatitis (Viral) What Is Viral Hepatitis? Hepatitis A Hepatitis B ...

  12. The Hepatitis B Virus (HBV) HBx Protein Activates AKT To Simultaneously Regulate HBV Replication and Hepatocyte Survival

    Science.gov (United States)

    Rawat, Siddhartha

    2014-01-01

    ABSTRACT Chronic infection with hepatitis B virus (HBV) is a risk factor for developing liver diseases such as hepatocellular carcinoma (HCC). HBx is a multifunctional protein encoded by the HBV genome; HBx stimulates HBV replication and is thought to play an important role in the development of HBV-associated HCC. HBx can activate the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in some cell lines; however, whether HBx regulates PI3K/AKT signaling in normal hepatocytes has not been evaluated. In studies described here, we assessed HBx activation of PI3K/AKT signaling in an ex vivo model of cultured primary hepatocytes and determined how this HBx activity affects HBV replication. We report that HBx activates AKT in primary hepatocytes and that the activation of AKT decreases HBV replication and HBV mRNA and core protein levels. We show that the transcription factor hepatocyte nuclear factor 4α (HNF4α) is a target of HBx-regulated AKT, and we link HNF4α to HBx-regulated AKT modulation of HBV transcription and replication. Although we and others have shown that HBx stimulates and is likely required for HBV replication, we now report that HBx also activates signals that can diminish the overall level of HBV replication. While this may seem counterintuitive, we show that an important effect of HBx activation of AKT is inhibition of apoptosis. Consequently, our studies suggest that HBx balances HBV replication and cell survival by stimulating signaling pathways that enhance hepatocyte survival at the expense of higher levels of HBV replication. IMPORTANCE Chronic hepatitis B virus (HBV) infection is a common cause of the development of liver cancer. Regulation of cell signaling pathways by the HBV HBx protein is thought to influence the development of HBV-associated liver cancer. HBx stimulates, and may be essential for, HBV replication. We show that HBx activates AKT in hepatocytes to reduce HBV replication. While this seems contradictory to an

  13. Natural Regulation of Energy Flow in a Green Quantum Photocell

    OpenAIRE

    Arp, Trevor B.; Barlas, Yafis; Aji, Vivek; Gabor, Nathaniel M.

    2015-01-01

    Manipulating the flow of energy in nanoscale and molecular photonic devices is of both fundamental interest and central importance for applications in light harvesting optoelectronics. Under erratic solar irradiance conditions, unregulated power fluctuations in a light harvesting photocell lead to inefficient energy storage in conventional solar cells and potentially fatal oxidative damage in photosynthesis. Here, we show that regulation against these fluctuations arises naturally within a tw...

  14. Cigarette smoking and brain regulation of energy homeostasis

    OpenAIRE

    Hui eChen; Hui eChen; Sonia eSaad; Shaun eSandow; Paul eBertrand

    2012-01-01

    Cigarette smoking is an addictive behaviour, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causin...

  15. Cigarette Smoking and Brain Regulation of Energy Homeostasis

    OpenAIRE

    Chen, Hui; Saad, Sonia; Sandow, Shaun L.; Bertrand, Paul P.

    2012-01-01

    Cigarette smoking is an addictive behavior, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing...

  16. Commission for Energy regulation (CRE) - Activity report june 2008

    International Nuclear Information System (INIS)

    2008-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  17. Regulation of hepatic peroxisome proliferator-activated receptor alpha expression but not adiponectin by dietary protein in finishing pigs.

    Science.gov (United States)

    Weber, T E; Kerr, B J; Spurlock, M E

    2008-10-01

    Soy protein regulates adiponectin and peroxisome proliferator-activated receptor alpha (PPARalpha) in some species, but the effect of dietary soy protein on adiponectin and PPARalpha in the pig has not been studied. Therefore, the objective of this study was to determine whether soya bean meal reduction or replacement influences serum adiponectin, adiponectin mRNA, serum metabolites and the expression of PPARalpha and other genes involved in lipid deposition. Thirty-three pigs (11 pigs per treatment) were subjected to one of three dietary treatments: (i) reduced crude protein (CP) diet containing soya bean meal (RCP-Soy), (ii) high CP diet containing soya bean meal (HCP-Soy) or (iii) high CP diet with corn gluten meal replacing soya bean meal (HCP-CGM) for 35 days. Dietary treatment had no effect on overall growth performance, feed intake or measures of body composition. There was no effect of dietary treatment on serum adiponectin or leptin. Dietary treatment did not affect the abundance of the mRNAs for adiponectin, PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthase in adipose tissue. The mRNA expression of PPARalpha, PPARgamma2, lipoprotein lipase or fatty acid synthetase in loin muscle was not affected by dietary treatment. In liver tissue, the relative abundance of PPARalpha mRNA was greater (p Soy diets when compared to pigs fed RCP-Soy or HCP-CGM diets. Hepatic mRNA expression of acyl-CoA oxidase or fatty acid synthase was not affected by dietary treatment. Western blot analysis indicated that hepatic PPARalpha protein levels were decreased (p Soy diets when compared to pigs fed the HCP-Soy diets. These data suggest that increasing the soy protein content of swine diets increases hepatic expression of PPARalpha without associated changes in body composition.

  18. Commission for Energy regulation (CRE) - Activity report June 2007

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  19. Commission for Energy regulation (CRE) - Activity report June 2007

    International Nuclear Information System (INIS)

    2007-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets, Natural gas

  20. Commission for Energy regulation (CRE) - Activity report June 2004

    International Nuclear Information System (INIS)

    2004-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2004 activity report of CRE. Content: A - Opening of the gas and electricity markets for professional customers on 1 July 2004; B - Regulation of the gas market: Gas markets and players (The European environment, The French gas market); Regulation of the gas market (Implementing regulation, Works planned for the coming year; C - Regulation of the electricity market: The electricity markets and players (The European electricity markets, The French electricity market, Monitoring the electricity market); Regulation of the French electricity market (Access to public grid, Cross-border exchanges, Un-bundled accounting principles); The public electricity service in the regulated market (Content of the public service, Public service charges, Electricity production public service financing, Electricity sales tariffs) D - The working of CRE: How CRE exercises its jurisdiction, Tools; E - Appendices: Glossary, Units and conversions, Council of European Energy Regulators, Index of tables and figures

  1. Commission for Energy regulation (CRE) - Activity report June 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2004 activity report of CRE. Content: A - Opening of the gas and electricity markets for professional customers on 1 July 2004; B - Regulation of the gas market: Gas markets and players (The European environment, The French gas market); Regulation of the gas market (Implementing regulation, Works planned for the coming year; C - Regulation of the electricity market: The electricity markets and players (The European electricity markets, The French electricity market, Monitoring the electricity market); Regulation of the French electricity market (Access to public grid, Cross-border exchanges, Un-bundled accounting principles); The public electricity service in the regulated market (Content of the public service, Public service charges, Electricity production public service financing, Electricity sales tariffs) D - The working of CRE: How CRE exercises its jurisdiction, Tools; E - Appendices: Glossary, Units and conversions, Council of European Energy Regulators, Index of tables and figures.

  2. Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice.

    Science.gov (United States)

    Xiao, Chun; Wu, Qingping; Zhang, Jumei; Xie, Yizhen; Cai, Wen; Tan, Jianbin

    2017-01-20

    Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin. Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These

  3. Present problems with atomic energy laws and regulations. 2. ed.

    International Nuclear Information System (INIS)

    Bluemel, W.

    1993-01-01

    The report includes two speeches held by the author on the 3rd Japanese-German Atomic Law Symposion in Tokio on 5-7 Oct. 1992. The titles are: 1) Recent developments in the German Laws and regulations ruling atomic energy; 2) Legal aspects of stopping and eliminating nuclear plants in Germany. Both speeches were translated into Japanese. (HP) [de

  4. PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Pei-Jie; Cai, Shuang-Peng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun, E-mail: lj@ahmu.edu.cn

    2016-02-01

    Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-β1 (TGF-β1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-β1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target. - Highlights: • The expression of PTP1B in the fibrotic livers and recovery livers • The expression of PTP1B in activated and inactivated HSCs • Blockade of PTP1B inhibited the TGF-β1-induced proliferation and activation of HSCs. • Over-expression of PTP1B abolished the inactivation of HSCs induced by MDI.

  5. PTP1B confers liver fibrosis by regulating the activation of hepatic stellate cells

    International Nuclear Information System (INIS)

    Chen, Pei-Jie; Cai, Shuang-Peng; Yang, Yang; Li, Wan-Xia; Huang, Cheng; Meng, Xiao-Ming; Li, Jun

    2016-01-01

    Liver fibrosis is a reversible wound-healing response to chronic hepatic injuries. Activation of hepatic stellate cells (HSCs) plays a pivotal role in the development of hepatic fibrosis. The currently accepted mechanism for the resolution of liver fibrosis is the apoptosis and inactivation of activated HSCs. Protein tyrosine phosphatase 1B (PTP1B), a prototype of non-receptor protein tyrosine phosphatase, is proved to be a vital modulator in cardiac fibrogenesis. However, the precise role of PTP1B on liver fibrosis and HSC activation is still unclear. Our study showed that the expression of PTP1B was elevated in fibrotic liver but reduced after spontaneous recovery. Moreover, stimulation of HSC-T6 cells with transforming growth factor-β1 (TGF-β1) resulted in a dose/time-dependent increase of PTP1B mRNA and protein. Co-incubation of HSC-T6 cells with PTP1B-siRNA inhibited the cell proliferation and activation induced by TGF-β1. Additionally, both mRNA and protein of PTP1B were dramatically decreased in inactivated HSCs after treated with adipogenic differentiation mixture (MDI). Over-expression of PTP1B hindered the inactivation of HSC-T6 cells induced by MDI. These observations revealed a regulatory role of PTP1B in liver fibrosis and implied PTP1B as a potential therapeutic target. - Highlights: • The expression of PTP1B in the fibrotic livers and recovery livers • The expression of PTP1B in activated and inactivated HSCs • Blockade of PTP1B inhibited the TGF-β1-induced proliferation and activation of HSCs. • Over-expression of PTP1B abolished the inactivation of HSCs induced by MDI.

  6. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

    Science.gov (United States)

    Jiao, Yang; Lu, Yan; Li, Xiao-ying

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia. PMID:25500875

  7. Actual energy consumption in dwellings. The effect of energy performance regulations and occupant behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Guerra Santin, O.

    2010-10-19

    Residential buildings have continuously improved in energy efficiency, partly as a consequence of the introduction of energy regulations in many countries. Although better thermal properties and systems efficiency have lowered energy consumption for space heating in recent decades, substantial differences in energy consumption in similar dwellings are still being observed. These differences in consumption are thought to be caused by differences in occupancy patterns, by quality of construction and by rebound effects. This research addresses the effect of energy performance regulations and occupant behavior on energy consumption for space and water heating in dwellings built after the introduction of the energy performance regulations in the Netherlands. The results of this research show that improving the energy efficiency of buildings alone is not enough to decrease that energy consumption. The large differences found in the use of dwellings indicate that, especially in energy efficient houses, occupant behavior provides an opportunity for further reductions in the energy consumption for space heating which could boost the efforts to conserve energy worldwide.

  8. Economic growth and energy regulation in the environmental Kuznets curve.

    Science.gov (United States)

    Lorente, Daniel Balsalobre; Álvarez-Herranz, Agustín

    2016-08-01

    This study establishes the existence of a pattern of behavior, between economic growth and environmental degradation, consistent with the environmental Kuznets curve (EKC) hypothesis for 17 Organization for Economic Cooperation and Development (OECD) countries between 1990 and 2012. Based on this EKC pattern, it shows that energy regulation measures help reduce per capita greenhouse gas (GHG) emissions. To validate this hypothesis, we also add the explanatory variables: renewable energy promotion, energy innovation processes, and the suppression effect of income level on the contribution of renewable energy sources to total energy consumption. It aims to be a tool for decision-making regarding energy policy. This paper provides a two-stage econometric analysis of instrumental variables with the aim of correcting the existence of endogeneity in the variable GDP per capita, verifying that the instrumental variables used in this research are appropriate for our aim. To this end, it first makes a methodological contribution before incorporating additional variables associated with environmental air pollution into the EKC hypothesis and showing how they positively affect the explanation of the correction in the GHG emission levels. This study concludes that air pollution will not disappear on its own as economic growth increases. Therefore, it is necessary to promote energy regulation measures to reduce environmental pollution.

  9. Evolving Role of the Power Sector Regulator: A Clean Energy Regulators Initiative Report

    Energy Technology Data Exchange (ETDEWEB)

    Zinaman, O.; Miller, M.; Bazilian, M.

    2014-04-01

    This paper seeks to briefly characterize the evolving role of power sector regulation. Given current global dynamics, regulation of the power sector is undergoing dramatic changes. This transformation is being driven by various factors including technological advances and cost reductions in renewable energy, energy efficiency, and demand management; increasing air pollution and climate change concerns; and persistent pressure for ensuring sustainable economic development and increased access to energy services by the poor. These issues add to the already complex task of power sector regulation, of which the fundamental remit remains to objectively and transparently ensure least-cost service delivery at high quality. While no single regulatory task is trivial to undertake, it is the prioritization and harmonization of a multitude of objectives that exemplifies the essential challenge of power sector regulation. Evolving regulatory roles can be understood through the concept of existing objectives and an additional layer of emerging objectives. Following this categorization, we describe seven existing objectives of power sector regulators and nine emerging objectives, highlighting key challenges and outlining interdependencies. This essay serves as a preliminary installment in the Clean Energy Regulatory Initiative (CERI) series, and aims to lay the groundwork for subsequent reports and case studies that will explore these topics in more depth.

  10. Intelligent energy systems - Regulating the electricity grid using car batteries

    International Nuclear Information System (INIS)

    Horbaty, R.

    2009-01-01

    This article takes a look at how the electricity supply industry will, in the future, be able to substantially rely on decentrally organised sources of renewable energy. As such forms of power generation are, in part, difficult to plan, the increasing importance of regulating energy is being stressed. The use of the batteries of plug-in hybrid vehicles to provide such regulating power is discussed. So-called smart grids within the framework of a deregulated energy market are discussed and examples of possible configurations are noted. The intelligent control of apparatus and generation and storage facilities is discussed. Individual mobility with lower emissions is examined. New business areas now opening up for the electricity economy and vehicle manufacturers are discussed.

  11. Environmental Policies, Product Market Regulation and Innovation in Renewable Energy

    International Nuclear Information System (INIS)

    Nesta, Lionel; Vona, Francesco; Nicolli, Francesco

    2012-10-01

    We investigate the effectiveness of policies in favor of innovation in renew- able energy under different levels of competition. Using information regarding renewable energy policies, product market regulation and high-quality green patents for OECD countries since the late 1970's, we develop a pre-sample mean count-data econometric specification that also accounts for the endogeneity of policies. We find that renewable energy policies are significantly more effective in fostering green innovation in countries with deregulated energy markets. We also find that public support for renewable energy is crucial only in the generation of high-quality green patents, whereas competition enhances the generation of green patents irrespective of their quality. (authors)

  12. Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation

    International Nuclear Information System (INIS)

    Yan, Jun; Lu, Qian; Dong, Jiahong; Li, Xiaowu; Ma, Kuansheng; Cai, Lei

    2012-01-01

    To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx). The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied. Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001). HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression

  13. Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity.

    Science.gov (United States)

    Ozcan, Lale; Wong, Catherine C L; Li, Gang; Xu, Tao; Pajvani, Utpal; Park, Sung Kyu Robin; Wronska, Anetta; Chen, Bi-Xing; Marks, Andrew R; Fukamizu, Akiyoshi; Backs, Johannes; Singer, Harold A; Yates, John R; Accili, Domenico; Tabas, Ira

    2012-05-02

    Hepatic glucose production (HGP) is crucial for glucose homeostasis, but the underlying mechanisms have not been fully elucidated. Here, we show that a calcium-sensing enzyme, CaMKII, is activated in a calcium- and IP3R-dependent manner by cAMP and glucagon in primary hepatocytes and by glucagon and fasting in vivo. Genetic deficiency or inhibition of CaMKII blocks nuclear translocation of FoxO1 by affecting its phosphorylation, impairs fasting- and glucagon/cAMP-induced glycogenolysis and gluconeogenesis, and lowers blood glucose levels, while constitutively active CaMKII has the opposite effects. Importantly, the suppressive effect of CaMKII deficiency on glucose metabolism is abrogated by transduction with constitutively nuclear FoxO1, indicating that the effect of CaMKII deficiency requires nuclear exclusion of FoxO1. This same pathway is also involved in excessive HGP in the setting of obesity. These results reveal a calcium-mediated signaling pathway involved in FoxO1 nuclear localization and hepatic glucose homeostasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Compensatory Changes in Energy Balance Regulation over One Athletic Season.

    Science.gov (United States)

    Silva, Analiza M; Matias, Catarina N; Santos, Diana A; Thomas, Diana; Bosy-Westphal, Anja; MüLLER, Manfred J; Heymsfield, Steven B; Sardinha, LUíS B

    2017-06-01

    Mechanisms in energy balance (EB) regulation may include compensatory changes in energy intake (EI) and metabolic adaption (MA), but information is unavailable in athletes who often change EB components. We aim to investigate EB regulation compensatory mechanisms over one athletic season. Fifty-seven athletes (39 males/18 females; handball, volleyball, basketball, triathlon, and swimming) were evaluated from the beginning to the competitive phase of the season. Resting and total energy expenditure (REE and TEE, respectively) were assessed by indirect calorimetry and doubly labeled water, respectively, and physical activity energy expenditure was determined as TEE - 0.1(TEE) - REE. Fat mass (FM) and fat-free mass (FFM) were evaluated by dual-energy x-ray absorptiometry and changed body energy stores was determined by 1.0(ΔFFM/Δtime) + 9.5(ΔFM/Δtime). EI was derived as TEE + EB. REE was predicted from baseline FFM, FM, sex, and sports. %MA was calculated as 100(measured REE/predicted REE-1) and MA (kcal) as %MA/100 multiplied by baseline measured REE. Average EI minus average physical activity energy expenditure was computed as a proxy of average energy availability, assuming that a constant nonexercise EE occurred over the season. Body mass increased by 0.8 ± 2.5 kg (P energy availability (r = 0.356 and r = 0.0644, respectively). TEE increased over the season without relevant mean changes in weight, suggesting that EI compensation likely occurred. The thrifty or spendthrift phenotypes observed among sports and the demanding workloads these athletes are exposed to highlight the need for sport-specific energy requirements.

  15. Transcription of hepatitis B virus covalently closed circular DNA is regulated by CpG methylation during chronic infection.

    Directory of Open Access Journals (Sweden)

    Yongmei Zhang

    Full Text Available The persistence of hepatitis B virus (HBV infection is maintained by the nuclear viral covalently closed circular DNA (cccDNA, which serves as transcription template for viral mRNAs. Previous studies suggested that cccDNA contains methylation-prone CpG islands, and that the minichromosome structure of cccDNA is epigenetically regulated by DNA methylation. However, the regulatory effect of each CpG island methylation on cccDNA activity remains elusive. In the present study, we analyzed the distribution of CpG methylation within cccDNA in patient samples and investigated the impact of CpG island methylation on cccDNA-driven virus replication. Our study revealed the following observations: 1 Bisulfite sequencing of cccDNA from chronic hepatitis B patients indicated that CpG island I was seldom methylated, 2 CpG island II methylation was correlated to the low level of serum HBV DNA in patients, and in vitro methylation studies confirmed that CpG island II methylation markedly reduced cccDNA transcription and subsequent viral core DNA replication, 3 CpG island III methylation was associated with low serum HBsAg titers, and 4 Furthermore, we found that HBV genotype, HBeAg positivity, and patient age and liver fibrosis stage were also relevant to cccDNA CpG methylation status. Therefore, we clearly demonstrated that the status of cccDNA methylation is connected to the biological behavior of HBV. Taken together, our study provides a complete profile of CpG island methylation within HBV cccDNA and new insights for the function of CpG methylation in regulating HBV cccDNA transcription.

  16. Changes in expression of hepatic genes involved in energy metabolism during hibernation in captive, adult, female Japanese black bears (Ursus thibetanus japonicus).

    Science.gov (United States)

    Shimozuru, Michito; Kamine, Akari; Tsubota, Toshio

    2012-10-01

    Hibernating bears survive up to 6 months without feeding by utilizing stored body fat as fuel. To investigate how bears maintain energy homeostasis during hibernation, we analyzed changes in mRNA expression of hepatic genes involved in energy metabolism throughout the hibernation period in captive, adult, female Japanese black bears (Ursus thibetanus japonicus). Real-time PCR analysis revealed down-regulation of glycolysis- (e.g., glucokinase), amino acid catabolism- (e.g., alanine aminotransferase) and de novo lipogenesis-related genes (e.g., acetyl-CoA carboxylase 1), and up-regulation of gluconeogensis- (e.g., pyruvate carboxylase), β-oxidation- (i.e., uncoupling protein 2) and ketogenesis-related genes (i.e., 3-hydroxy-3-methylglutary-CoA synthase 2), during hibernation, compared to the active period (June). In addition, we found that glycolysis-related genes (i.e., glucokinase and pyruvate kinase) were more suppressed in the early phase of hibernation (January) compared to the late phase (March). One week after the commencement of feeding in April, expression levels of most genes returned to levels comparable to those seen in June, but β-oxidation-related genes were still up-regulated during this period. These results suggest that the modulation of gene expression is not static, but changes throughout the hibernation period. The transcriptional modulation during hibernation represents a unique physiological adaptation to prolonged fasting in bears. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Serum hyaluronic acid predicts protein-energy malnutrition in chronic hepatitis C.

    Science.gov (United States)

    Nishikawa, Hiroki; Enomoto, Hirayuki; Yoh, Kazunori; Iwata, Yoshinori; Hasegawa, Kunihiro; Nakano, Chikage; Takata, Ryo; Kishino, Kyohei; Shimono, Yoshihiro; Sakai, Yoshiyuki; Nishimura, Takashi; Aizawa, Nobuhiro; Ikeda, Naoto; Takashima, Tomoyuki; Ishii, Akio; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-06-01

    Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0-6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6-6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0-783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001).In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC.

  18. Does energy-price regulation benefit China's economy and environment? Evidence from energy-price distortions

    International Nuclear Information System (INIS)

    Ju, Keyi; Su, Bin; Zhou, Dequn; Wu, Junmin

    2017-01-01

    China's energy prices have long been regulated due to the critical role energy plays in economic growth and social development, which leads to energy-price distortion to some extent. To figure out whether energy-price regulations will benefit China's economy (measured by GDP growth) and environment (measured by carbon emissions), we conducted an in-depth simulation using path analysis, where five energy products (natural gas, gasoline, fuel oil, steam coal, and coking coal) are selected and three measurements (absolute, relative, and moving) of energy-price distortions are calculated. The results indicate that, with a series of energy pricing policies, the price distortion for a single type of energy has gradually transformed, while the energy pricing system in China is not fully market-oriented yet. Furthermore, China's economy benefits from relative and moving distortions, while the absolute distortions of energy prices have negative impacts on economic growth. Finally, with regard to the environment, carbon emissions call for fewer distortions. - Highlights: • Price distortion for a single type of energy has gradually transformed. • Energy pricing system in China is not yet fully market-oriented. • China's economy benefits from relative and moving distortions. • Absolute distortions of energy prices have negative effects on economic growth. • Carbon emissions call for less pricing distortions.

  19. SOR/88-144, Atomic Energy Control Regulations, amendment

    International Nuclear Information System (INIS)

    1988-01-01

    These amendments dated 25 February 1988 mainly concern naturally-occurring radioactive prescribed substances (namely, uranium, thorium, radium, etc.). Any naturally-occurring radioactive material in a mineral or other material which has not been related to an activity associated with the development, application or use of atomic energy, is exempted from the scope of the Regulations. The Regulations will therefore not apply to such radioactive substances present in building materials or in minerals commonly used in industrial activities which are not associated with the nuclear fuel cycle. This exemption does not apply to such material in connection with import control and preparation for transport. (NEA)

  20. Upper intestinal lipids regulate energy and glucose homeostasis.

    Science.gov (United States)

    Cheung, Grace W C; Kokorovic, Andrea; Lam, Tony K T

    2009-09-01

    Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced gut-brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal lipid-induced gut-brain-liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids.

  1. Metabolic regulation of neuronal plasticity by the energy sensor AMPK.

    Directory of Open Access Journals (Sweden)

    Wyatt B Potter

    Full Text Available Long Term Potentiation (LTP is a leading candidate mechanism for learning and memory and is also thought to play a role in the progression of seizures to intractable epilepsy. Maintenance of LTP requires RNA transcription, protein translation and signaling through the mammalian Target of Rapamycin (mTOR pathway. In peripheral tissue, the energy sensor AMP-activated Protein Kinase (AMPK negatively regulates the mTOR cascade upon glycolytic inhibition and cellular energy stress. We recently demonstrated that the glycolytic inhibitor 2-deoxy-D-glucose (2DG alters plasticity to retard epileptogenesis in the kindling model of epilepsy. Reduced kindling progression was associated with increased recruitment of the nuclear metabolic sensor CtBP to NRSF at the BDNF promoter. Given that energy metabolism controls mTOR through AMPK in peripheral tissue and the role of mTOR in LTP in neurons, we asked whether energy metabolism and AMPK control LTP. Using a combination of biochemical approaches and field-recordings in mouse hippocampal slices, we show that the master regulator of energy homeostasis, AMPK couples energy metabolism to LTP expression. Administration of the glycolytic inhibitor 2-deoxy-D-glucose (2DG or the mitochondrial toxin and anti-Type II Diabetes drug, metformin, or AMP mimetic AICAR results in activation of AMPK, repression of the mTOR pathway and prevents maintenance of Late-Phase LTP (L-LTP. Inhibition of AMPK by either compound-C or the ATP mimetic ara-A rescues the suppression of L-LTP by energy stress. We also show that enhanced LTP via AMPK inhibition requires mTOR signaling. These results directly link energy metabolism to plasticity in the mammalian brain and demonstrate that AMPK is a modulator of LTP. Our work opens up the possibility of using modulators of energy metabolism to control neuronal plasticity in diseases and conditions of aberrant plasticity such as epilepsy.

  2. Proceedings of the 8. Brazilian congress on energy: energy policy, regulation and sustainable development. v. 2: energy planning and policy, energy conservation and rational use

    International Nuclear Information System (INIS)

    1999-01-01

    The theme energy policy, regulation and sustainable development chosen for the 8. Brazilian congress on energy to be held in Rio de Janeiro from 30 November of 1999 to 02 December of 1999, specifically means the contribution of energy to a satisfactory quality of life for everyone. Within such a context, the congress technical programme theme has been structured around six different divisions: energy, environment and development; energy sector regulation; energy policy and planning; technology innovation; energy conservation; and renewable energy sources and rural areas energy supply

  3. Efficiency analysis of energy networks: An international survey of regulators

    International Nuclear Information System (INIS)

    Haney, Aoife Brophy; Pollitt, Michael G.

    2009-01-01

    Incentive regulation for networks has been an important part of the reform agenda in a number of countries. As part of this regulatory process, incentives are put in place to improve the cost efficiency of network companies by rewarding good performance relative to a pre-defined benchmark. The techniques used to establish benchmarks are central to the efficiency improvements that are ultimately achieved. Much experience has been gained internationally in the application of benchmarking techniques and we now have a solid understanding of the main indicators of best practice. What we are lacking is a more complete understanding of the factors that influence choice of methods by regulators. In this paper, we present the results of an international survey of energy regulators in 40 countries conducted electronically between June and October 2008. Regulators from European, Australasian and Latin American countries are represented in the survey. Our results show that benchmarking techniques are now widespread in the regulation of gas and electricity networks. Best practice, however, is limited to a small number of regulators. We conclude by summarising existing trends and offering some recommendations on overcoming barriers to best practice efficiency analysis.

  4. Optimal Scheduling of an Regional Integrated Energy System with Energy Storage Systems for Service Regulation

    Directory of Open Access Journals (Sweden)

    Hengrui Ma

    2018-01-01

    Full Text Available Ancillary services are critical to maintaining the safe and stable operation of power systems that contain a high penetration level of renewable energy resources. As a high-quality regulation resource, the regional integrated energy system (RIES with energy storage system (ESS can effectively adjust the non-negligible frequency offset caused by the renewable energy integration into the power system, and help solve the problem of power system frequency stability. In this paper, the optimization model aiming at regional integrated energy system as a participant in the regulation market based on pay-for-performance is established. Meanwhile YALMIP + CPLEX is used to simulate and analyze the total operating cost under different dispatch modes. This paper uses the actual operation model of the PJM regulation market to guide the optimal allocation of regulation resource in the regional integrated energy system, and provides a balance between the power trading revenue and regulation market revenue in order to achieve the maximum profit.

  5. Cadm2 regulates body weight and energy homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Xin Yan

    2018-02-01

    Full Text Available Objective: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI and multiple loci near Cell adhesion molecule2 (CADM2, which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain. Methods: We first analyzed Cadm2 expression in the brain of both human subjects and mouse models and subsequently characterized a loss-of-function mouse model of Cadm2 for alterations in glucose and energy homeostasis. Results: We show that the risk variant rs13078960 associates with increased CADM2 expression in the hypothalamus of human subjects. Increased Cadm2 expression in several brain regions of Lepob/ob mice was ameliorated after leptin treatment. Deletion of Cadm2 in obese mice (Cadm2/ob resulted in reduced adiposity, systemic glucose levels, and improved insulin sensitivity. Cadm2-deficient mice exhibited increased locomotor activity, energy expenditure rate, and core body temperature identifying Cadm2 as a potent regulator of systemic energy homeostasis. Conclusions: Together these data illustrate that reducing Cadm2 expression can reverse several traits associated with the metabolic syndrome including obesity, insulin resistance, and impaired glucose homeostasis. Keywords: Cadm2/SynCAM2, Energy homeostasis, Insulin sensitivity, Genome-wide association studies, Leptin signaling

  6. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign Liver Tumors Biliary Atresia Cirrhosis of the ... Disease Type 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of ...

  7. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns ... are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty Liver ...

  8. The regulation, the key for the development of renewable energies

    International Nuclear Information System (INIS)

    Saez de Miera, G.

    2007-01-01

    Regulation, rather than mere availability of resources-water, wind, sun-, is the key factor for an appropriate development of the renewable energies. A comparative analysis of the main regulatory support schemes feed-in-tariffs, green certificates and auctions is done in this paper, concluding that systems based on feed-in-tariff are more efficient and effective. Finally, we describe and analyze the regulatory arrangements in place to support wind energy in Spain, a well-known worldwide success, which is based on three basic foundations: predictability, stability and sufficiency. (Author)

  9. Intelligent Glazed Facades for Fulfilment of Future Energy Regulations

    DEFF Research Database (Denmark)

    Winther, Frederik Vildbrad; Heiselberg, Per; Jensen, Rasmus Lund

    2010-01-01

    This project aims at testing technologies for control of heat transfer, irradiation, mass transport and energy storage in order to investigate the potential of a intelligent dynamic glazed facade. Furthermore a development of algorithms for control of the technologies included in the facade......, for use in the design phase, is done. The methods used are initially based on thermal building calculations. This analysis shows that a dynamic adaptive facade is the only way in which future office buildings can fulfil the energy regulations. By designing the facade according to the usage...

  10. Effects of ovariectomy and exercise training intensity on energy substrate and hepatic lipid metabolism, and spontaneous physical activity in mice.

    Science.gov (United States)

    Tuazon, Marc A; Campbell, Sara C; Klein, Dylan J; Shapses, Sue A; Anacker, Keith R; Anthony, Tracy G; Uzumcu, Mehmet; Henderson, Gregory C

    2018-06-01

    Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Price regulation in the Spanish energy sectors: who benefits?

    International Nuclear Information System (INIS)

    Arocena, Pablo; Contin, Ignacio; Huerta, Emilio

    2002-01-01

    This paper analyses the distribution of benefits between firms and consumers due to the price regulation of the Spanish energy sectors (electricity, oil fuels and gas) during the decade 1987-1997. To that effect, we compare the actual evolution of energy prices with alternate benchmarks in order to assess the potential existence of a pro-industry or a pro-consumer bias in the pricing policies followed by the regulator. Our results show a pro-industry-biased regulatory context, where consumers benefited very little from price control. The successive price adjustments over time allowed the companies to keep all the productivity gains and cost reductions and to increase their profitability rates relative to those achieved in the manufacturing sector. (Author)

  12. Price regulation in the Spanish energy sectors: who benefits?

    Energy Technology Data Exchange (ETDEWEB)

    Arocena, Pablo; Contin, Ignacio; Huerta, Emilio [Departamento de Gestion de Empresas, Universidad Publica de Navarra, Campus de Arrosadia. 31006, Pamplona (Spain); [Canterbury Business School, University of Kent Canterbury (United Kingdom)

    2002-08-01

    This paper analyses the distribution of benefits between firms and consumers due to the price regulation of the Spanish energy sectors (electricity, oil fuels and gas) during the decade 1987-1997. To that effect, we compare the actual evolution of energy prices with alternate benchmarks in order to assess the potential existence of a pro-industry or a pro-consumer bias in the pricing policies followed by the regulator. Our results show a pro-industry-biased regulatory context, where consumers benefited very little from price control. The successive price adjustments over time allowed the companies to keep all the productivity gains and cost reductions and to increase their profitability rates relative to those achieved in the manufacturing sector. (Author)

  13. The effect of building regulations and energy conservation measures in domestic sector on national energy consumption

    International Nuclear Information System (INIS)

    Samo, S.R.; Akhund, M.A.; Brohi, K.M.

    2004-01-01

    In England, housing accounts for some 30% of total fuel consumption and a similar proportion of energy-related carbon dioxide (CO/sub 2/) emission. A study has been conducted to analyse the effect of the legislations and UK thermal building regulations on national energy consumption in housing. This research paper presents data on the percentage of dwelling stock, the energy consumption, energy cost and carbon dioxide (CO/sub 2/) emission in different types of dwellings, which comply different building regulations from 1965 to 1995. It was found that. 66% of the dwelling stock, which comply the building Regulations before 1965, consumes 73% of total energy used in housing. This dwelling stock is also responsible for 75% of carbon dioxide (CO/sub 2/) emission. Whereas currently only 4% of the dwelling stock complies the latest building regulations 1995 which consume 2 % of energy and produce a similar percentage of carbon dioxide (CO/sub 2/) emission in housing. Since the large portion of the dwelling stock is comprised of old dwellings, therefore the greatest potential for energy conservation measures can be found in improving these dwellings instead of constructing new dwellings. (author)

  14. The relative importance of kinetic mechanisms and variable enzyme abundances for the regulation of hepatic glucose metabolism--insights from mathematical modeling.

    Science.gov (United States)

    Bulik, Sascha; Holzhütter, Hermann-Georg; Berndt, Nikolaus

    2016-03-02

    Adaptation of the cellular metabolism to varying external conditions is brought about by regulated changes in the activity of enzymes and transporters. Hormone-dependent reversible enzyme phosphorylation and concentration changes of reactants and allosteric effectors are the major types of rapid kinetic enzyme regulation, whereas on longer time scales changes in protein abundance may also become operative. Here, we used a comprehensive mathematical model of the hepatic glucose metabolism of rat hepatocytes to decipher the relative importance of different regulatory modes and their mutual interdependencies in the hepatic control of plasma glucose homeostasis. Model simulations reveal significant differences in the capability of liver metabolism to counteract variations of plasma glucose in different physiological settings (starvation, ad libitum nutrient supply, diabetes). Changes in enzyme abundances adjust the metabolic output to the anticipated physiological demand but may turn into a regulatory disadvantage if sudden unexpected changes of the external conditions occur. Allosteric and hormonal control of enzyme activities allow the liver to assume a broad range of metabolic states and may even fully reverse flux changes resulting from changes of enzyme abundances alone. Metabolic control analysis reveals that control of the hepatic glucose metabolism is mainly exerted by enzymes alone, which are differently controlled by alterations in enzyme abundance, reversible phosphorylation, and allosteric effects. In hepatic glucose metabolism, regulation of enzyme activities by changes of reactants, allosteric effects, and reversible phosphorylation is equally important as changes in protein abundance of key regulatory enzymes.

  15. Commission for Energy regulation (CRE) - Activity report June 2005

    International Nuclear Information System (INIS)

    2005-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2005 activity report of CRE. Content: A - The opening of the markets in France and in Europe: The opening of the markets one year after 1 July 2004 (An especially important step, Electricity and gas: a common framework with structural differences, The coexistence of market prices and regulated tariffs); The European texts of 26 June 2003 (Texts to give new impetus, Texts to harmonize the role and powers of national regulators, Texts to guarantee the independence of system operators, Texts to ensure transparent and non-discriminatory access to networks, Texts providing for strengthening of interconnections); The outlook for 2007, a fully open market (1 July 2007: a date set by the directives, Priority given to informing and protecting consumers); B - Regulation of the natural gas market: The gas market in the European context (Europe's dependency on imports is increasing, Gas prices increased considerably across the whole of Europe in 2004, The European gas scene continues to be dominated by a small number of players, Gas infrastructures need to be developed in Europe, The new European

  16. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

    Science.gov (United States)

    Timper, Katharina; Brüning, Jens C.

    2017-01-01

    ABSTRACT The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. PMID:28592656

  17. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity.

    Science.gov (United States)

    Timper, Katharina; Brüning, Jens C

    2017-06-01

    The 'obesity epidemic' represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed. © 2017. Published by The Company of Biologists Ltd.

  18. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity

    Directory of Open Access Journals (Sweden)

    Katharina Timper

    2017-06-01

    Full Text Available The ‘obesity epidemic’ represents a major global socioeconomic burden that urgently calls for a better understanding of the underlying causes of increased weight gain and its associated metabolic comorbidities, such as type 2 diabetes mellitus and cardiovascular diseases. Improving our understanding of the cellular basis of obesity could set the stage for the development of new therapeutic strategies. The CNS plays a pivotal role in the regulation of energy and glucose homeostasis. Distinct neuronal cell populations, particularly within the arcuate nucleus of the hypothalamus, sense the nutrient status of the organism and integrate signals from peripheral hormones including pancreas-derived insulin and adipocyte-derived leptin to regulate calorie intake, glucose metabolism and energy expenditure. The arcuate neurons are tightly connected to other specialized neuronal subpopulations within the hypothalamus, but also to various extrahypothalamic brain regions, allowing a coordinated behavioral response. This At a Glance article gives an overview of the recent knowledge, mainly derived from rodent models, regarding the CNS-dependent regulation of energy and glucose homeostasis, and illustrates how dysregulation of the neuronal networks involved can lead to overnutrition and obesity. The potential impact of recent research findings in the field on therapeutic treatment strategies for human obesity is also discussed.

  19. Regulation of Danish energy markets with imperfect competition

    International Nuclear Information System (INIS)

    Goertz, M.; Hansen, J.V.

    1999-01-01

    In this paper we use a new CGE model of the Danish economy with the acronym ECOSMEC (Economic COuncil Simulation Model with Energy markets and Carbon taxation). The model is a hybrid of two existing static models developed by respectively the Secretariat of the Danish Economic Council and by the MobiDK project in the Ministry of Business and Industry. Distinct features of the ECOSMEC model are a rather disaggregated modelling of energy demand and supply, introduction of various market structures in the energy sector, and a consistent specification of different household types. The simulations presented in the paper have the following implications: First, a uniform CO 2 tax of approximately 300 DKK per ton CO 2 could reduce emissions by 20 per cent in a scenario with perfect competition in the energy sector. However, assuming different market structures in the energy sector influences the uniform CO 2 tax needed to reach a given emission target. In the paper we assume that the Danish energy sector is a natural monopoly regulated to comply with average cost pricing, but we also discuss alternative descriptions of imperfect competition. Second, the empirical arguments for differentiated CO 2 taxes motivated by imperfect energy markets are weak. This is in line with earlier international studies on environmental taxes and imperfect competition. Third, the Danish economy could benefit from a deregulation of the electricity and district heating sector with respect to welfare and economic activity. This result holds also if CO 2 emissions are kept constant. (au)

  20. Promoting nuclear energy: market price or regulated tariffs? - 5042

    International Nuclear Information System (INIS)

    Percebois, J.

    2015-01-01

    Because of its negative effects, the scheme for aiding renewable energies presently in force in Europe is likely to penalise investments in nuclear energy. The F.I.T. system is a costly mechanism and a source of perverse effects as a switching of the merit order curve on the spot electricity market (with sometimes negative prices). Restoring an equity and 'equal opportunity' for nuclear energy in Europe needs to implement a 'Contract for Differences' scheme for nuclear energy, like the model now gaining favour in the U.K. The contract for differences signed between EDF and the UK government means that if the wholesale price that EDF secures for Hinckley's power falls below the index-linked preset value, the difference will be covered by payments from the UK government. It appears that nuclear power has weakened in Europe by the system of guaranteed purchase prices for renewable energies. Moreover this system is costly. New fairer rules must be implemented in the market. Either the market is left on its own to send the signals to all investors (including renewable energies), or a minimum of regulation is introduced in order to limit the costly surges of under and over capacity. But in the latter case it is necessary to treat all the energy sources in an equal way and guarantee the nuclear industry that it will also recover its fixed costs over the long term)

  1. IL-8 signaling is up-regulated in alcoholic hepatitis and DDC fed mice with Mallory Denk Bodies (MDBs) present.

    Science.gov (United States)

    Liu, Hui; French, Barbara A; Nelson, Tyler J; Li, Jun; Tillman, Brittany; French, Samuel W

    2015-10-01

    Chemokines and their receptors are involved in oncogenesis and in tumor progression, invasion, and metastasis. Various chemokines also promote cell proliferation and resistance to apoptosis of stressed cells. The chemokine CXCL8, also known as interleukin-8 (IL-8), is a proinflammatory molecule that has functions within the tumor microenvironment. Deregulation of IL-8 signaling is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of IL-8 signaling by RNA sequencing (RNA-Seq) analyses. Real-time PCR analysis of CXCR2 further shows a 6-fold up-regulation in AH livers and a 26-fold up-regulation in the livers of DDC re-fed mice. IL-8 mRNA was also significantly up-regulated in AH livers and DDC re-fed mice livers. This indicates that CXCR2 and IL-8 may be crucial for liver MDB formation. MDB containing balloon hepatocytes in AH livers had increased intensity of staining of the cytoplasm for both CXCR2 and IL-8. Overexpression of IL-8 leads to an increase of the mitogen activated protein kinase (MAPK) cascade and exacerbates the inflammatory cycle. These observations constitute a demonstration of the altered regulation of IL-8 signaling in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by IL-8 signaling in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.

    Science.gov (United States)

    Kraft, G; Ortigues-Marty, I; Durand, D; Rémond, D; Jardé, T; Bequette, B; Savary-Auzeloux, I

    2011-04-01

    We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body

  3. AMP-Activated Protein Kinase (AMPK) Regulates Energy Metabolism through Modulating Thermogenesis in Adipose Tissue

    Science.gov (United States)

    Wu, Lingyan; Zhang, Lina; Li, Bohan; Jiang, Haowen; Duan, Yanan; Xie, Zhifu; Shuai, Lin; Li, Jia; Li, Jingya

    2018-01-01

    Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), which is specialized in dissipating energy through thermogenesis, potently counteracts obesity. White adipocytes can be converted to thermogenic “brown-like” cells (beige cells; WAT browning) under various stimuli, such as cold exposure. AMP-activated protein kinase (AMPK) is a crucial energy sensor that regulates energy metabolism in multiple tissues. However, the role of AMPK in adipose tissue function, especially in the WAT browning process, is not fully understood. To illuminate the effect of adipocyte AMPK on energy metabolism, we generated Adiponectin-Cre-driven adipose tissue-specific AMPK α1/α2 KO mice (AKO). These AKO mice were cold intolerant and their inguinal WAT displayed impaired mitochondrial integrity and biogenesis, and reduced expression of thermogenic markers upon cold exposure. High-fat-diet (HFD)-fed AKO mice exhibited increased adiposity and exacerbated hepatic steatosis and fibrosis and impaired glucose tolerance and insulin sensitivity. Meanwhile, energy expenditure and oxygen consumption were markedly decreased in the AKO mice both in basal conditions and after stimulation with a β3-adrenergic receptor agonist, CL 316,243. In contrast, we found that in HFD-fed obese mouse model, chronic AMPK activation by A-769662 protected against obesity and related metabolic dysfunction. A-769662 alleviated HFD-induced glucose intolerance and reduced body weight gain and WAT expansion. Notably, A-769662 increased energy expenditure and cold tolerance in HFD-fed mice. A-769662 treatment also induced the browning process in the inguinal fat depot of HFD-fed mice. Likewise, A-769662 enhanced thermogenesis in differentiated inguinal stromal vascular fraction (SVF) cells via AMPK signaling pathway. In summary, a lack of adipocyte AMPKα induced thermogenic impairment and obesity in response to cold and nutrient-overload, respectively

  4. Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

    Science.gov (United States)

    Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

    2001-01-01

    Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

  5. High-fructose corn syrup, energy intake, and appetite regulation.

    Science.gov (United States)

    Melanson, Kathleen J; Angelopoulos, Theodore J; Nguyen, Von; Zukley, Linda; Lowndes, Joshua; Rippe, James M

    2008-12-01

    High-fructose corn syrup (HFCS) has been implicated in excess weight gain through mechanisms seen in some acute feeding studies and by virtue of its abundance in the food supply during years of increasing obesity. Compared with pure glucose, fructose is thought to be associated with insufficient secretion of insulin and leptin and suppression of ghrelin. However, when HFCS is compared with sucrose, the more commonly consumed sweetener, such differences are not apparent, and appetite and energy intake do not differ in the short-term. Longer-term studies on connections between HFCS, potential mechanisms, and body weight have not been conducted. The main objective of this review was to examine collective data on associations between consumption of HFCS and energy balance, with particular focus on energy intake and its regulation.

  6. A Role for Mitochondrial Phosphoenolpyruvate Carboxykinase (PEPCK-M) in the Regulation of Hepatic Gluconeogenesis*

    Science.gov (United States)

    Stark, Romana; Guebre-Egziabher, Fitsum; Zhao, Xiaojian; Feriod, Colleen; Dong, Jianying; Alves, Tiago C.; Ioja, Simona; Pongratz, Rebecca L.; Bhanot, Sanjay; Roden, Michael; Cline, Gary W.; Shulman, Gerald I.; Kibbey, Richard G.

    2014-01-01

    Synthesis of phosphoenolpyruvate (PEP) from oxaloacetate is an absolute requirement for gluconeogenesis from mitochondrial substrates. Generally, this reaction has solely been attributed to the cytosolic isoform of PEPCK (PEPCK-C), although loss of the mitochondrial isoform (PEPCK-M) has never been assessed. Despite catalyzing the same reaction, to date the only significant role reported in mammals for the mitochondrial isoform is as a glucose sensor necessary for insulin secretion. We hypothesized that this nutrient-sensing mitochondrial GTP-dependent pathway contributes importantly to gluconeogenesis. PEPCK-M was acutely silenced in gluconeogenic tissues of rats using antisense oligonucleotides both in vivo and in isolated hepatocytes. Silencing PEPCK-M lowers plasma glucose, insulin, and triglycerides, reduces white adipose, and depletes hepatic glycogen, but raises lactate. There is a switch of gluconeogenic substrate preference to glycerol that quantitatively accounts for a third of glucose production. In contrast to the severe mitochondrial deficiency characteristic of PEPCK-C knock-out livers, hepatocytes from PEPCK-M-deficient livers maintained normal oxidative function. Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. Thus, PEPCK-M has a direct role in fasted and fed glucose homeostasis, and this mitochondrial GTP-dependent pathway should be reconsidered for its involvement in both normal and diabetic metabolism. PMID:24497630

  7. A role for mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) in the regulation of hepatic gluconeogenesis.

    Science.gov (United States)

    Stark, Romana; Guebre-Egziabher, Fitsum; Zhao, Xiaojian; Feriod, Colleen; Dong, Jianying; Alves, Tiago C; Ioja, Simona; Pongratz, Rebecca L; Bhanot, Sanjay; Roden, Michael; Cline, Gary W; Shulman, Gerald I; Kibbey, Richard G

    2014-03-14

    Synthesis of phosphoenolpyruvate (PEP) from oxaloacetate is an absolute requirement for gluconeogenesis from mitochondrial substrates. Generally, this reaction has solely been attributed to the cytosolic isoform of PEPCK (PEPCK-C), although loss of the mitochondrial isoform (PEPCK-M) has never been assessed. Despite catalyzing the same reaction, to date the only significant role reported in mammals for the mitochondrial isoform is as a glucose sensor necessary for insulin secretion. We hypothesized that this nutrient-sensing mitochondrial GTP-dependent pathway contributes importantly to gluconeogenesis. PEPCK-M was acutely silenced in gluconeogenic tissues of rats using antisense oligonucleotides both in vivo and in isolated hepatocytes. Silencing PEPCK-M lowers plasma glucose, insulin, and triglycerides, reduces white adipose, and depletes hepatic glycogen, but raises lactate. There is a switch of gluconeogenic substrate preference to glycerol that quantitatively accounts for a third of glucose production. In contrast to the severe mitochondrial deficiency characteristic of PEPCK-C knock-out livers, hepatocytes from PEPCK-M-deficient livers maintained normal oxidative function. Consistent with its predicted role, gluconeogenesis rates from hepatocytes lacking PEPCK-M are severely reduced for lactate, alanine, and glutamine, but not for pyruvate and glycerol. Thus, PEPCK-M has a direct role in fasted and fed glucose homeostasis, and this mitochondrial GTP-dependent pathway should be reconsidered for its involvement in both normal and diabetic metabolism.

  8. Immune and Metabolic Regulation Mechanism of Dangguiliuhuang Decoction against Insulin Resistance and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Hui Cao

    2017-07-01

    Full Text Available Dangguiliuhuang decoction (DGLHD is a traditional Chinese medicine (TCM formula, which mainly consists of angelica, radix rehmanniae, radix rehmanniae praeparata, scutellaria baicalensis, coptis chinensis, astragalus membranaceus, and golden cypress, and used for the treatment of diabetes and some autoimmune diseases. In this study, we explored the potential mechanism of DGLHD against insulin resistance and fatty liver in vivo and in vitro. Our data revealed that DGLHD normalized glucose and insulin level, increased the expression of adiponectin, diminished fat accumulation and lipogenesis, and promoted glucose uptake. Metabolomic analysis also demonstrated that DGLHD decreased isoleucine, adenosine, and cholesterol, increased glutamine levels in liver and visceral adipose tissue (VAT of ob/ob mice. Importantly, DGLHD promoted the shift of pro-inflammatory to anti-inflammatory cytokines, suppressed T lymphocytes proliferation, and enhanced regulatory T cells (Tregs differentiation. DGLHD also inhibited dendritic cells (DCs maturation, attenuated DCs-stimulated T cells proliferation and secretion of IL-12p70 cytokine from DCs, and promoted the interaction of DCs with Tregs. Further studies indicated that the changed PI3K/Akt signaling pathway and elevated PPAR-γ expression were not only observed with the ameliorated glucose and lipid metabolism in adipocytes and hepatocytes, but also exhibited in DCs and T cells by DGLHD. Collectively, our results suggest that DGLHD exerts anti-insulin resistant and antisteatotic effects by improving abnormal immune and metabolic homeostasis. And DGLHD may be a novel approach to the treatment of obesity-related insulin resistance and hepatic steatosis.

  9. Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

    Science.gov (United States)

    Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

    2007-10-01

    Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

  10. Didymin Alleviates Hepatic Fibrosis Through Inhibiting ERK and PI3K/Akt Pathways via Regulation of Raf Kinase Inhibitor Protein

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    Xing Lin

    2016-12-01

    Full Text Available Background: Didymin has been reported to have anti-cancer potential. However, the effect of didymin on liver fibrosis remains illdefined. Methods: Hepatic fibrosis was induced by CCl4 in rats. The effects of didymin on liver pathology and collagen accumulation were observed by hematoxylin-eosin and Masson's trichrome staining, respectively. Serum transaminases activities and collagen-related indicators levels were determined by commercially available kits. Moreover, the effects of didymin on hepatic stellate cell apoptosis and cell cycle were analyzed by flow cytometry. Mitochondrial membrane potential was detected by using rhodamine-123 dye. The expression of Raf kinase inhibitor protein (RKIP and the phosphorylation of the ERK/MAPK and PI3K/Akt pathways were assessed by Western blot. Results: Didymin significantly ameliorated chronic liver injury and collagen deposition. It strongly inhibited hepatic stellate cells proliferation, induced apoptosis and caused cell cycle arrest in G2/M phase. Moreover, didymin notably attenuated mitochondrial membrane potential, accompanied by release of cytochrome C. Didymin significantly inhibited the ERK/MAPK and PI3K/Akt pathways. The effects of didymin on the collagen accumulation in rats and on the biological behaviors of hepatic stellate cells were largely abolished by the specific RKIP inhibitor locostatin. Conclusion: Didymin alleviates hepatic fibrosis by inhibiting ERK/MAPK and PI3K/Akt pathways via regulation of RKIP expression.

  11. Regulation of the energy infrastructure. Load management. Part 1. Fiscal aspects of energy networks

    International Nuclear Information System (INIS)

    Smits, L.

    2008-01-01

    The Dutch energy system depends on the presence of a good infrastructure. For many decades little attention was paid to infrastructure, but due to the liberalization infrastructure is receiving renewed attention. The grids are now considered the backbone of the energy system and essential for security of supply. Moreover, future electricity plants may have to adhere to the 'zero emission' demands in the future and (nearly) empty oil and gas fields will be used for underground storage of substances such as CO2. This new series addresses the existing and new regulation for the energy infrastructure. This edition addresses a number of fiscal aspects of the energy infrastructure. [mk] [nl

  12. p300/CBP as a Key Nutritional Sensor for Hepatic Energy Homeostasis and Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Weilei Yao

    2018-01-01

    Full Text Available The overwhelming frequency of metabolic diseases such as obesity and diabetes are closely related to liver diseases, which might share common pathogenic signaling processes. These metabolic disorders in the presence of inflammatory response seem to be triggered by and to reside in the liver, which is the central metabolic organ that plays primary roles in regulating lipid and glucose homeostasis upon alterations of metabolic conditions. Recently, abundant emerging researches suggested that p300 and CREB binding protein (CBP are crucial regulators of energy homeostasis and liver fibrosis through both their acetyltransferase activities and transcriptional coactivators. Plenty of recent findings demonstrated the potential roles of p300/CBP in mammalian metabolic homeostasis in response to nutrients. This review is focused on the different targets and functions of p300/CBP in physiological and pathological processes, including lipogenesis, lipid export, gluconeogenesis, and liver fibrosis, also provided some nutrients as the regulator of p300/CBP for nutritional therapeutic approaches to treat liver diseases.

  13. The nuclear retinoid-related orphan receptor-α regulates adipose tissue glyceroneogenesis in addition to hepatic gluconeogenesis.

    Science.gov (United States)

    Kadiri, Sarah; Monnier, Chloé; Ganbold, Munkhzul; Ledent, Tatiana; Capeau, Jacqueline; Antoine, Bénédicte

    2015-07-15

    Circadian rhythms have an essential role in feeding behavior and metabolism. RORα is a nuclear receptor involved in the interface of the circadian system and metabolism. The adipocyte glyceroneogenesis pathway derives free fatty acids (FFA) liberated by lipolysis to reesterification into triglycerides, thus regulating FFA homeostasis and fat mass. Glyceroneogenesis shares with hepatic gluconeogenesis the key enzyme phosphoenolpyruvate carboxykinase c (PEPCKc), whose gene is a RORα target in the liver. RORα-deficient mice (staggerer, ROR(sg/sg)) have been shown to exhibit a lean phenotype and fasting hypoglycemia for unsolved reasons. In the present study, we investigated whether adipocyte glyceroneogenesis might also be a target pathway of RORα, and we further evaluated the role of RORα in hepatocyte gluconeogenesis. In vivo investigations comparing ROR(sg/sg) mice with their wild-type (WT) littermates under fasting conditions demonstrated that, in the absence of RORα, the release of FFA into the bloodstream was altered and the rise in glycemia in response to pyruvate reduced. The functional analysis of each pathway, performed in adipose tissue or liver explants, confirmed the impairment of adipocyte glyceroneogenesis and liver gluconeogenesis in the ROR(sg/sg) mice; these reductions of FFA reesterification or glucose production were associated with decreases in PEPCKc mRNA and protein levels. Treatment of explants with RORα agonist or antagonist enhanced or inhibited these pathways, respectively, in tissues isolated from WT but not ROR(sg/sg) mice. Our results indicated that both adipocyte glyceroneogenesis and hepatocyte gluconeogenesis were regulated by RORα. This study demonstrates the physiological function of RORα in regulating both glucose and FFA homeostasis. Copyright © 2015 the American Physiological Society.

  14. Evidence for dual control mechanism regulating hepatic glucose output in nondiabetic men

    International Nuclear Information System (INIS)

    Clore, J.N.; Glickman, P.S.; Helm, S.T.; Nestler, J.E.; Blackard, W.G.

    1991-01-01

    The authors previously reported a fall in hepatic glucose output (HGO) during sleep accompanied by reductions in glucose utilization (Rd) and free fatty acids (FFAs). This study was undertaken to determine the potential role of changes in Rd and FFA on HGO in nondiabetic men. To determine if the fall in HGO during sleep could be reversed by FFA elevation, seven nondiabetic men underwent [3-3H]glucose infusions from 2200 to 0800, with heparin (90 mU.kg-1.min-1) added at 0200. Glucose appearance (Ra) fell from 11.7 ± 1.1 at 2430 to 8.9 ± 0.8 mumol.kg-1.min-1 (P less than 0.05) at 0200. The fall in Ra was associated with decreases in FFA (0.57 ± 0.10 to 0.48 ± 0.07 mM) and glycerol (0.08 ± 0.01 to 0.06 ± 0.01 mM). Infusion of heparin significantly increased FFA and glycerol (1.09 ± 0.21 and 0.11 ± 0.01 mM, respectively, P less than 0.01) and resulted in a significant fall in plasma alanine, suggesting that gluconeogenesis had been increased. However, rates of glucose turnover were indistinguishable from overnight studies without heparin. In additional studies (n = 6), intralipid and heparin-induced FFA elevation (from 0.61 ± 0.07 to 0.95 ± 0.05 mM, P less than 0.01) stimulated gluconeogenesis ([U-14C]alanine to glucose) twofold (188 ± 22% increase compared to 114 ± 6% in saline control studies, P less than 0.01). However, despite increasing gluconeogenesis, overall HGO did not change (10.6 ± 0.5 vs. 10.7 ± 0.6 mumol.kg-1.min-1) during lipid infusion

  15. Maltase-glucoamylase: Mucosal regulator of prandial starch glucogenesis and complementary hepatic gluconeogenesis of mice

    Science.gov (United States)

    It was hypothesized that the slower rate of starch digestion by residual sucraseisomaltase (Si) maltase failed to fully regulate gluconeogenesis. In the present study the rate of gluconeogenesis was measured directly (J Appl Physiol 104: 944-951, 2008) and compared with exogenous glucose derived fro...

  16. Maltase-glucoamylase: Mucosal regulator of prandial starch glucogenesis and complimentary hepatic gluconeogenesis of mice

    Science.gov (United States)

    In previous studies we have shown that maltase-glucoamylase (Mgam) is required for efficient starch digestion and insulin response to starch feeding. It was hypothesized that the slower rate of starch digestion by residual sucrase-isomaltase (Si) maltase failed to regulate gluconeogenesis. Here, rat...

  17. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    Ni, Xunjun; Wang, Haiyan

    2016-01-01

    Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

  18. Obstructive sleep apnea and energy balance regulation: A systematic review.

    Science.gov (United States)

    Shechter, Ari

    2017-08-01

    Obesity and obstructive sleep apnea (OSA) have a reciprocal relationship. Sleep disruptions characteristic of OSA may promote behavioral, metabolic, and/or hormonal changes favoring weight gain and/or difficulty losing weight. The regulation of energy balance (EB), i.e., the relationship between energy intake (EI) and energy expenditure (EE), is complex and multi-factorial, involving food intake, hormonal regulation of hunger/satiety/appetite, and EE via metabolism and physical activity (PA). The current systematic review describes the literature on how OSA affects EB-related parameters. OSA is associated with a hormonal profile characterized by abnormally high leptin and ghrelin levels, which may encourage excess EI. Data on actual measures of food intake are lacking, and not sufficient to make conclusions. Resting metabolic rate appears elevated in OSA vs. Findings on PA are inconsistent, but may indicate a negative relationship with OSA severity that is modulated by daytime sleepiness and body weight. A speculative explanation for the positive EB in OSA is that the increased EE via metabolism induces an overcompensation in the drive for hunger/food intake, which is larger in magnitude than the rise in EI required to re-establish EB. Understanding how OSA affects EB-related parameters can help improve weight loss efforts in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Cigarette smoking and brain regulation of energy homeostasis

    Directory of Open Access Journals (Sweden)

    Hui eChen

    2012-07-01

    Full Text Available Cigarette smoking is an addictive behaviour, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases. Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing a negative energy state which is characterized by reduced energy intake and increased energy expenditure that are linked to low body weight. These findings have led to the public perception that smoking is associated with weight loss. However, its effects at reducing abdominal fat mass (a predisposing factor for glucose intolerance and insulin resistance are marginal, and its promotion of lean body mass loss in animal studies suggests a limited potential for treatment in obesity. Smoking during pregnancy puts pressure on the mother’s metabolic system and is a significant contributor to adverse pregnancy outcomes. Smoking is a predictor of future risk for respiratory dysfunction, social behavioral problems, cardiovascular disease, obesity and type-2 diabetes. Catch-up growth is normally observed in children exposed to intrauterine smoke, which has been linked to subsequent childhood obesity. Nicotine can have a profound impact on the developing fetal brain, via its ability to rapidly and fully pass the placenta. In animal studies this has been linked with abnormal hypothalamic gene expression of appetite regulators such as downregulation of NPY and POMC in the arcuate nucleus of the hypothalamus. Maternal smoking or nicotine replacement leads to unhealthy eating habits (such as junk food addiction and other behavioral disorders in the offspring.

  20. Cigarette smoking and brain regulation of energy homeostasis.

    Science.gov (United States)

    Chen, Hui; Saad, Sonia; Sandow, Shaun L; Bertrand, Paul P

    2012-01-01

    Cigarette smoking is an addictive behavior, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing a negative energy state which is characterized by reduced energy intake and increased energy expenditure that are linked to low body weight. These findings have led to the public perception that smoking is associated with weight loss. However, its effects at reducing abdominal fat mass (a predisposing factor for glucose intolerance and insulin resistance) are marginal, and its promotion of lean body mass loss in animal studies suggests a limited potential for treatment in obesity. Smoking during pregnancy puts pressure on the mother's metabolic system and is a significant contributor to adverse pregnancy outcomes. Smoking is a predictor of future risk for respiratory dysfunction, social behavioral problems, cardiovascular disease, obesity, and type-2 diabetes. Catch-up growth is normally observed in children exposed to intrauterine smoke, which has been linked to subsequent childhood obesity. Nicotine can have a profound impact on the developing fetal brain, via its ability to rapidly and fully pass the placenta. In animal studies this has been linked with abnormal hypothalamic gene expression of appetite regulators such as downregulation of NPY and POMC in the arcuate nucleus of the hypothalamus. Maternal smoking or nicotine replacement leads to unhealthy eating habits (such as junk food addiction) and other behavioral disorders in the offspring.

  1. COMPETITION AND REGULATION IN THE EU ENERGY MARKET

    Directory of Open Access Journals (Sweden)

    Cristina Havriş

    2009-12-01

    Full Text Available When prices are high and public service obligations are not properly fulfilled, consumers wonder if they obtain what they need from the market. In electricity and gas markets of the EU Member States, apart from the persistence of high, non-transparent regulated prices, a number of shortcomings have been identified by the European Commission, such as a less than optimal network use for energy transmission, a lack of coordination and cooperation across borders by transmission system operators and national authorities, and a lack of transparent and simple procedures for dealing with consumers’ complaints. These are the main elements of the infringement proceedings that the European Commission decided to launch on 25 June 2009 against 25 Member States for non–compliance with certain Community provisions in the Second Internal Energy Market Package, which entered into force on 1 July 2007. Quite emblematic is the fact that it occurred the same day as the adoption of the Third Internal Energy Market Package aiming to ensure a proper functioning of the EU energy market. We intend to analyse what has happened in the recent years at the EU level in order to liberalise and remove the significant remaining obstacles to competition in the energy market.

  2. Work Programme 2010. Nordic Energy Regulators (NordREG)

    Energy Technology Data Exchange (ETDEWEB)

    2010-02-15

    The Nordic regulators' cooperation through NordREG is based on a strong consensus and common understanding of the Nordic market. Through mutual efforts and contributions NordREG members identify areas of work that can create added value for the Nordic electricity market. NordREG works by exchanging information and views, mapping and analysing energy market issues and by delivering statements and reports for harmonisation and improvement. In this, the regulators aim at identifying areas where NordREG can take joint action to influence Nordic or European electricity market development. NordREGs key focus in 2010 is the work towards a common Nordic retail market and the emphasis is on promoting a legal and institutional framework that supports this goal

  3. CART in the Regulation of Appetite and Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Jackie eLau

    2014-10-01

    Full Text Available The cocaine- and amphetamine-regulated transcript (CART has been the subject of significant interest for over a decade. Work to decipher the detailed mechanism of CART function has been hampered by the lack of specific pharmacological tools like antagonists and the absence of a specific CART receptor(s. However, extensive research has been devoted to elucidate the role of the CART peptide and it is now evident that CART is a key neurotransmitter and hormone involved in the regulation of diverse biological processes, including food intake, maintenance of body weight, reward and addiction, stress response, psychostimulant effects and endocrine functions1,2. In this review, we focus on knowledge gained on CART’s role in controlling appetite and energy homeostasis, and also address certain species differences between rodents and humans.

  4. Delineating the regulation of energy homeostasis using hypothalamic cell models.

    Science.gov (United States)

    Wellhauser, Leigh; Gojska, Nicole M; Belsham, Denise D

    2015-01-01

    Attesting to its intimate peripheral connections, hypothalamic neurons integrate nutritional and hormonal cues to effectively manage energy homeostasis according to the overall status of the system. Extensive progress in the identification of essential transcriptional and post-translational mechanisms regulating the controlled expression and actions of hypothalamic neuropeptides has been identified through the use of animal and cell models. This review will introduce the basic techniques of hypothalamic investigation both in vivo and in vitro and will briefly highlight the key advantages and challenges of their use. Further emphasis will be place on the use of immortalized models of hypothalamic neurons for in vitro study of feeding regulation, with a particular focus on cell lines proving themselves most fruitful in deciphering fundamental basics of NPY/AgRP, Proglucagon, and POMC neuropeptide function. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Commission for Energy regulation (CRE) - Activity report june 2006

    International Nuclear Information System (INIS)

    2006-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2006 activity report of CRE. Content: A - Opening of the electricity and natural gas markets to household consumers on 1 July 2007: CRE at the service of eligible customers (Information for eligible customers, Improved knowledge of non-household customers); Monitoring of the non-discrimination, transparency and independence of system operators (Drafting and distribution of codes of good conduct for system operators, The necessary improvement of system operator independence); Preparing the practical methods of opening: GTE 2007 and GTG 2007 (The necessary simplification of relations between operators and customers, Achieving a greater level of consumer information and protection, The clearly defined stages of the 'customer pathway', Profiling and settlement mechanisms: turning experience feedback from 2004 to good account); Persisting uncertainties and hurdles (The need for a suitable regulatory and legislative platform, Hurdles to the opening of the household market); B - Regulation of the natural gas market: The gas market in the European context (Increasing weight of imports in gas

  6. Commission for Energy regulation (CRE) - Activity report june 2006

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2006 activity report of CRE. Content: A - Opening of the electricity and natural gas markets to household consumers on 1 July 2007: CRE at the service of eligible customers (Information for eligible customers, Improved knowledge of non-household customers); Monitoring of the non-discrimination, transparency and independence of system operators (Drafting and distribution of codes of good conduct for system operators, The necessary improvement of system operator independence); Preparing the practical methods of opening: GTE 2007 and GTG 2007 (The necessary simplification of relations between operators and customers, Achieving a greater level of consumer information and protection, The clearly defined stages of the 'customer pathway', Profiling and settlement mechanisms: turning experience feedback from 2004 to good account); Persisting uncertainties and hurdles (The need for a suitable regulatory and legislative platform, Hurdles to the opening of the household market); B - Regulation of the natural gas market: The gas market in the European context (Increasing weight of

  7. Modulation of hepatic inflammation and energy-sensing pathways in the rat liver by high-fructose diet and chronic stress.

    Science.gov (United States)

    Veličković, Nataša; Teofilović, Ana; Ilić, Dragana; Djordjevic, Ana; Vojnović Milutinović, Danijela; Petrović, Snježana; Preitner, Frederic; Tappy, Luc; Matić, Gordana

    2018-05-29

    High-fructose consumption and chronic stress are both associated with metabolic inflammation and insulin resistance. Recently, disturbed activity of energy sensor AMP-activated protein kinase (AMPK) was recognized as mediator between nutrient-induced stress and inflammation. Thus, we analyzed the effects of high-fructose diet, alone or in combination with chronic stress, on glucose homeostasis, inflammation and expression of energy sensing proteins in the rat liver. In male Wistar rats exposed to 9-week 20% fructose diet and/or 4-week chronic unpredictable stress we measured plasma and hepatic corticosterone level, indicators of glucose homeostasis and lipid metabolism, hepatic inflammation (pro- and anti-inflammatory cytokine levels, Toll-like receptor 4, NLRP3, activation of NFκB, JNK and ERK pathways) and levels of energy-sensing proteins AMPK, SIRT1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). High-fructose diet led to glucose intolerance, activation of NFκB and JNK pathways and increased intrahepatic IL-1β, TNFα and inhibitory phosphorylation of insulin receptor substrate 1 on Ser 307 . It also decreased phospho-AMPK/AMPK ratio and increased SIRT1 expression. Stress alone increased plasma and hepatic corticosterone but did not influence glucose tolerance, nor hepatic inflammatory or energy-sensing proteins. After the combined treatment, hepatic corticosterone was increased, glucose tolerance remained preserved, while hepatic inflammation was partially prevented despite decreased AMPK activity. High-fructose diet resulted in glucose intolerance, hepatic inflammation, decreased AMPK activity and reduced insulin sensitivity. Chronic stress alone did not exert such effects, but when applied together with high-fructose diet it could partially prevent fructose-induced inflammation, presumably due to increased hepatic glucocorticoids.

  8. Weekend ethanol consumption and high-sucrose diet: resveratrol effects on energy expenditure, substrate oxidation, lipid profile, oxidative stress and hepatic energy metabolism.

    Science.gov (United States)

    Rocha, Katiucha Karolina Honório Ribeiro; Souza, Gisele Aparecida; Seiva, Fábio Rodrigues Ferreira; Ebaid, Geovana Xavier; Novelli, Ethel Lourenzi Barbosa

    2011-01-01

    The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, 3,5,4'-trans-trihydroxystilbene) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle. Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week. After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats. The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

  9. Oil price volatility, financial regulation and energy policy

    International Nuclear Information System (INIS)

    Chevalier, J.M.

    2010-01-01

    In October of 2009, the French Ministry of Economy asked the author to chair a work group on oil price volatility. The report resulting from that work was submitted to the minister on February 9, 2010. Based on the report, this article focuses on three major elements: (i) the operation of the oil market, with interacting physical basics and financial basics (ii) financial market regulation, more specifically commodities-derived product markets and current work in that area and (iii) the lessons one can draw from that exercise in terms of energy policy. Significant projects have been initiated on global, European and national levels. (author)

  10. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading

    OpenAIRE

    Makui, Hortence; Soares, Ricardo J.; Jiang, Wenlei; Constante, Marco; Santos, Manuela M.

    2005-01-01

    Hereditary hemochromatosis (HH), an iron overload disease associated with mutations in the HFE gene, is characterized by increased intestinal iron absorption and consequent deposition of excess iron, primarily in the liver. Patients with HH and Hfe-deficient (Hfe−/−) mice manifest inappropriate expression of the iron absorption regulator hepcidin, a peptide hormone produced by the liver in response to iron loading. In this study, we investigated the contribution of Hfe expression in macrophag...

  11. Mice with an Oncogenic HRAS Mutation are Resistant to High-Fat Diet-Induced Obesity and Exhibit Impaired Hepatic Energy Homeostasis

    Directory of Open Access Journals (Sweden)

    Daiju Oba

    2018-01-01

    Full Text Available Costello syndrome is a “RASopathy” that is characterized by growth retardation, dysmorphic facial appearance, hypertrophic cardiomyopathy and tumor predisposition. >80% of patients with Costello syndrome harbor a heterozygous germline G12S mutation in HRAS. Altered metabolic regulation has been suspected because patients with Costello syndrome exhibit hypoketotic hypoglycemia and increased resting energy expenditure, and their growth is severely retarded. To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (HrasG12S/+ mice as a mouse model of Costello syndrome. On a high-fat diet, HrasG12S/+ mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under starvation conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.

  12. Energy Density, Energy Intake, and Body Weight Regulation in Adults12345

    Science.gov (United States)

    Karl, J. Philip; Roberts, Susan B.

    2014-01-01

    The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight. PMID:25398750

  13. Shale Gas, the Environment and Energy Security : A New Framework For Energy Regulation

    NARCIS (Netherlands)

    Fleming, Ruven

    2017-01-01

    `This pioneering and in-depth study into the regulation of shale gas extraction examines how changes in the constitutional set-ups of EU Member States over the last 25 years have substantially altered the legal leverage of environmental protection and energy security as state objectives. As well as

  14. PRMT5: A novel regulator of Hepatitis B virus replication and an arginine methylase of HBV core.

    Directory of Open Access Journals (Sweden)

    Barbora Lubyova

    Full Text Available In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II enzyme responsible for the majority of symmetric dimethylarginine formation in polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV replication through epigenetic repression of HBV DNA transcription and interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5 interacts with the HBV core (HBc protein and dimethylates arginine residues within the arginine-rich domain (ARD of the carboxyl-terminus. ARD consists of four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis of ARDs revealed that arginine methylation of HBc required the wild-type status of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple potential ubiquitination, methylation and phosphorylation sites, out of which lysine K7 and arginines R150 (within ARDI and R156 (outside ARDs were shown to be modified by ubiquitination and methylation, respectively. The HBc symmetric dimethylation appeared to be linked to serine phosphorylation and nuclear import of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm. Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei of transfected cells. In summary, we identified PRMT5 as a potent controller of HBc cell trafficking and function and described two novel types of HBc post-translational modifications (PTMs, arginine methylation and ubiquitination.

  15. Regulation of international energy markets: Economic effects of political actions

    Science.gov (United States)

    Shcherbakova, Anastasia V.

    Recent increases in volatility of energy prices have led many governments to reevaluate their regard of national energy reserves and reconsider future exploration, production, and consumption patterns. The flurry of activity that has been generated by such price volatility has included large-scale nationalizations of energy sectors, unilateral renegotiations of foreign energy development contracts, and expropriations of resources from foreign energy firms on one hand, and on the other hand more rapid energy sector liberalization, intensified search for and development of renewable fuels and technologies, and development of incentives for increased energy efficiency and conservation. The aim of this dissertation is to examine and quantify the extent of positive and negative effects that have resulted from some of these activities. The first chapter focuses on quantifying the effect that nationalistic sentiment has had on economic attractiveness of energy sectors during the decade prior to the recent global economic crisis, as measured by foreign direct investment (FDI) inflows. Empirical results demonstrate that both political and economic conditions play an important role in investors' decisions. A combination of investment friendliness, corruption levels, and democracy all help to explain the trends in energy-sector investment levels over time in my sample countries, although differences in the types of corruption existing in these nations do not. Investment levels, in turn, appear to influence future levels of oil production, underscoring the significance of good investment policies for future success of energy sectors. Chapter two considers the response of energy stock prices to severe regulatory actions. It employs an event study framework to examine causal effects of critical informational announcements (i.e. events of expropriation and nationalization) on daily returns and cumulative losses in firm value of energy corporations. Results show that a firm

  16. The Methionine Transamination Pathway Controls Hepatic Glucose Metabolism through Regulation of the GCN5 Acetyltransferase and the PGC-1α Transcriptional Coactivator*

    OpenAIRE

    Tavares, Clint D. J.; Sharabi, Kfir; Dominy, John E.; Lee, Yoonjin; Isasa, Marta; Orozco, Jose M.; Jedrychowski, Mark P.; Kamenecka, Theodore M.; Griffin, Patrick R.; Gygi, Steven P.; Puigserver, Pere

    2016-01-01

    Methionine is an essential sulfur amino acid that is engaged in key cellular functions such as protein synthesis and is a precursor for critical metabolites involved in maintaining cellular homeostasis. In mammals, in response to nutrient conditions, the liver plays a significant role in regulating methionine concentrations by altering its flux through the transmethylation, transsulfuration, and transamination metabolic pathways. A comprehensive understanding of how hepatic methionine metabol...

  17. Regulation of hepatic lipogenesis by the transcription complex Prep1-Pbx1

    OpenAIRE

    Cabaro, Serena

    2011-01-01

    Prep1 is an homeodomain transcription factor belonging to the TALE proteins, including also Pbx1, which plays an essential role in hematopoiesis, organogenesis and development. Prep1 forms transcriptionally active complexes with Pbx1 and regulates the activity of several genes. The Prep1 null mutation leads to embryonic death at a very early stage. Therefore, Prep1 hypomorphic (Prep1i/i) mice have been generated. Prep1 heterozygous (Prep1i/+) mice, which express only 55-57% of protein, have a...

  18. Sort1, encoded by the cardiovascular risk locus 1p13.3, is a regulator of hepatic lipoprotein export

    DEFF Research Database (Denmark)

    Kjølby, Mads Fuglsang; Andersen, Olav Michael; Breiderhoff, Tilman

    2010-01-01

    of lipoproteins from the liver and ameliorates hypercholesterolemia and atherosclerotic lesion formation in LDL receptor-deficient animals. In contrast, sortilin overexpression stimulates hepatic release of lipoproteins and increases plasma LDL levels. Our data have uncovered a regulatory pathway in hepatic...... lipoprotein export and suggest a molecular explanation for the cardiovascular risk being associated with 1p13.3. Udgivelsesdato: september 8...

  19. Hepatitis A virus cellular receptor 2 (HAVCR2) is decreased with viral infection and regulates pro-labour mediators OA.

    Science.gov (United States)

    Liong, Stella; Lim, Ratana; Barker, Gillian; Lappas, Martha

    2017-07-01

    Intrauterine infection caused by viral infection has been implicated to contribute to preterm birth. Hepatitis A virus cellular receptor 2 (HAVCR2) regulates inflammation in non-gestational tissues in response to viral infection. The aims of this study were to determine the effect of: (i) viral dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) on HAVCR2 expression; and (ii) HAVCR2 silencing by siRNA (siHAVCR2) in primary amnion and myometrial cells on poly(I:C)-induced inflammation. In human foetal membranes and myometrium, HAVCR2 mRNA and protein expression was decreased when exposed to poly(I:C). Treatment of primary amnion and myometrial cells with poly(I:C) significantly increased the expression and release of pro-inflammatory cytokines TNF, IL1A, IL1B and IL6; the expression of chemokines CXCL8 and CCL2; the expression and secretion of adhesion molecules ICAM1 and VCAM1; and PTGS2 and PTGFR mRNA expression and the release of prostaglandin PGF 2α . This increase was significantly augmented in cells transfected with siHAVCR2. Furthermore, mRNA expression of anti-inflammatory cytokines IL4 and IL10 was significantly decreased. Collectively, our data suggest that HAVCR2 regulates cytokines, chemokines, prostaglandins and cell adhesion molecules in the presence of viral infection. This suggests a potential for HAVCR2 activators as therapeutics for the management of preterm birth associated with viral infections. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Regulation of Liver Energy Balance by the Nuclear Receptors Farnesoid X Receptor and Peroxisome Proliferator Activated Receptor α.

    Science.gov (United States)

    Kim, Kang Ho; Moore, David D

    2017-01-01

    The liver undergoes major changes in substrate utilization and metabolic output over the daily feeding and fasting cycle. These changes occur acutely in response to hormones such as insulin and glucagon, with rapid changes in signaling pathways mediated by protein phosphorylation and other post-translational modifications. They are also reflected in chronic alterations in gene expression in response to nutrient-sensitive transcription factors. Among these, the nuclear receptors farnesoid X receptor (FXR) and peroxisome proliferator activated receptor α (PPARα) provide an intriguing, coordinated response to maintain energy balance in the liver. FXR is activated in the fed state by bile acids returning to the liver, while PPARα is activated in the fasted state in response to the free fatty acids produced by adipocyte lipolysis or possibly other signals. Key Messages: Previous studies indicate that FXR and PPARα have opposing effects on each other's primary targets in key metabolic pathways including gluconeogenesis. Our more recent work shows that these 2 nuclear receptors coordinately regulate autophagy: FXR suppresses this pathway of nutrient and energy recovery, while PPARα activates it. Another recent study indicates that FXR activates the complement and coagulation pathway, while earlier studies identify this as a negative target of PPARα. Since secretion is a very energy- and nutrient-intensive process for hepatocytes, it is possible that FXR licenses it in the nutrient-rich fed state, while PPARα represses it to spare resources in the fasted state. Energy balance is a potential connection linking FXR and PPARα regulation of autophagy and secretion, 2 seemingly unrelated aspects of hepatocyte function. FXR and PPARα act coordinately to promote energy balance and homeostasis in the liver by regulating autophagy and potentially protein secretion. It is quite likely that their impact extends to additional pathways relevant to hepatic energy balance, and

  1. Financial markets regulation in the energy sector. A few financial aspects of energy transactions

    International Nuclear Information System (INIS)

    Simonetti, S.

    2007-01-01

    In addition to energy legislation, financial markets legislation and regulation (FMR) are becoming increasingly important for the energy sector. Consequently, parties on the energy market not only have to deal with the energy and competition authorities (the Dte and NMa respectively), but may also face supervision by The Netherlands Authority for the Financial Markets (AFM). Energy transactions may trigger certain prohibitions and obligations under financial and securities law, the most relevant of which are discussed in this article. Both the recent changes as a result of the Financial Markets Supervision Act ('Wet op het financieel toezicht', Wft) entering into force as per 1 January 2007 and the anticipated future amendments following the implementation of the Markets in Financial Instruments Directive (MiFID) are examined [nl

  2. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body.

    Directory of Open Access Journals (Sweden)

    Christal A Worthen

    2014-03-01

    Full Text Available Fine tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron-sensor, transferrin receptor 2 (TfR2, is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH. With the loss of functional TfR2, the liver produces about two-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin in the bloodstream, and hepatocytes treated with transferrin respond with a two-fold increase in hepcidin expression through stimulation of the BMP-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein (HFE, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

  3. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ... A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice In Newborns Diseases of the Liver ...

  4. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  5. Hepatitis B

    Science.gov (United States)

    ... B Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... in their blood (sometimes referred to as the hepatitis B viral load) and an unusually high level of a ...

  6. Parental Influences on Children's Self-Regulation of Energy Intake: Insights from Developmental Literature on Emotion Regulation

    Directory of Open Access Journals (Sweden)

    Leslie A. Frankel

    2012-01-01

    Full Text Available The following article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to children's behavior, assistance in helping children self-regulate, and motivating children through rewards and punishments. Additionally, sources of variation in parental influences on regulation are examined, including parenting style, child temperament, and child-parent attachment security. Parallels in the nature of parents' role in socializing children's regulation of emotions and energy intake are examined. Implications for future research are discussed.

  7. Circulating Glucagon 1-61 Regulates Blood Glucose by Increasing Insulin Secretion and Hepatic Glucose Production

    DEFF Research Database (Denmark)

    Wewer Albrechtsen, Nicolai J.; Kuhre, Rune E.; Hornburg, Daniel

    2017-01-01

    that PG 1-61 dose-dependently increases levels of cAMP, through the glucagon receptor, and increases insulin secretion and protein levels of enzymes regulating glycogenolysis and gluconeogenesis. In rats, PG 1-61 increases blood glucose and plasma insulin and decreases plasma levels of amino acids in......Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among...... which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after. Studies in hepatocytes and in β cells demonstrated...

  8. Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis.

    Science.gov (United States)

    Kojima, Misaki; Masui, Toshimitsu; Nemoto, Kiyomitsu; Degawa, Masakuni

    2004-12-01

    Changes in the gene expressions of hepatic enzymes responsible for cholesterol homeostasis were examined during the process of lead nitrate (LN)-induced development of hypercholesterolemia in male rats. Total cholesterol levels in the liver and serum were significantly increased at 3-72 h and 12-72 h, respectively, after LN-treatment (100 micromol/kg, i.v.). Despite the development of hypercholesterolemia, the genes for hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) and other enzymes (FPPS, farnesyl diphosphate synthase; SQS, squalene synthase; CYP51, lanosterol 14alpha-demethylase) responsible for cholesterol biosynthesis were activated at 3-24 h and 12-18 h, respectively. On the other hand, the gene expression of cholesterol 7alpha-hydroxylase (CYP7A1), a catabolic enzyme of cholesterol, was remarkably suppressed at 3-72 h. The gene expression levels of cytokines interleukin-1beta (IL-1beta) and TNF-alpha, which activate the HMGR gene and suppress the CYP7A1 gene, were significantly increased at 1-3 h and 3-24 h, respectively. Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51. This is the first report demonstrating sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis in LN-treated male rats. The mechanisms for the altered-gene expressions of hepatic enzymes in LN-treated rats are discussed.

  9. Bee's honey attenuates non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-NLRP3 inflammasome pathway.

    Science.gov (United States)

    Xiao, Jia; Liu, Yingxia; Xing, Feiyue; Leung, Tung Ming; Liong, Emily C; Tipoe, George L

    2016-06-01

    We aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (NASH) animal and cell line steatosis models. NASH was induced in female Sprague-Dawley rat by 8-week feeding with a high-fat diet. During the experiment, 5 g/kg honey was intragastrically fed daily. Rat normal hepatocyte BRL-3A cell was treated with sodium palmitate (SP) to induce steatosis in the absence or presence of honey pre-treatment or specific siRNA/overexpress plasmid of thioredoxin-interacting protein (TXNIP) or antagonist/agonist of Nod-like receptor protein 3 (NLRP3). Honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. Honey also inhibited the overexpression of TXNIP and the activation of NLRP3 inflammasome. These effects were replicated in BRL-3A cell line which showed that the down-regulation of TXNIP or inhibition of NLRP3 contributed to the suppression of NLRP3 inflammasome activation, inflammation, and re-balanced lipid metabolism. In contrast, overexpression of TXNIP or agonism of NLRP3 exacerbated the cellular damage induced by SP. Suppression of the TXNIP-NLRP3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of NASH by honey. Targeting hepatic TXNIP-NLRP3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of NASH.

  10. Sugary Kefir Strain Lactobacillus mali APS1 Ameliorated Hepatic Steatosis by Regulation of SIRT-1/Nrf-2 and Gut Microbiota in Rats.

    Science.gov (United States)

    Chen, Yung-Tsung; Lin, Yu-Chun; Lin, Jin-Seng; Yang, Ning-Sun; Chen, Ming-Ju

    2018-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). Sprague Dawley rats were fed a control diet, a HFD with saline, and a HFD with APS1 intervention by gavage daily for 12 weeks. The results showed that APS1 significantly reduced body weight and body weight gain in HFD-fed rats. APS1 reduced hepatic lipid accumulation by regulating SIRT-1/PGC-1α/SREBP-1 expression. Moreover, APS1 increased hepatic antioxidant activity by modulating Nrf-2/HO-1 expression. Notably, APS1 manipulated the gut microbiota, resulting in increasing proportions of the phylum Bacteroidetes/Firmicutes and reducing the abundance of specific NAFLD-associated bacteria. These results suggested that APS1 ameliorated hepatic steatosis by modulating lipid metabolism and antioxidant activity via manipulating specific NAFLD-associated gut microbiota in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. PHP14 regulates hepatic stellate cells migration in liver fibrosis via mediating TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway.

    Science.gov (United States)

    Xu, Anjian; Li, Yanmeng; Zhao, Wenshan; Hou, Fei; Li, Xiaojin; Sun, Lan; Chen, Wei; Yang, Aiting; Wu, Shanna; Zhang, Bei; Yao, Jingyi; Wang, Huan; Huang, Jian

    2018-02-01

    Hepatic fibrosis is characterized by the activation of hepatic stellate cells (HSCs). Migration of the activated HSCs to the site of injury is one of the key characteristics during the wound healing process. We have previously demonstrated that 14 kDa phosphohistidine phosphatase (PHP14) is involved in migration and lamellipodia formation of HSCs. However, the role of PHP14 in liver fibrosis remains unknown. In this study, we first assessed PHP14 expression and distribution in liver fibrotic tissues using western blot, immunohistochemistry, and double immunofluorescence staining. Next, we investigated the role of PHP14 in liver fibrosis and, more specifically, the migration of HSCs by Transwell assay and 3D collagen matrices assay. Finally, we explored the possible molecular mechanisms of the effects of PHP14 on these processes. Our results show that the PHP14 expression is up-regulated in fibrotic liver and mainly in HSCs. Importantly, TGF-β1 can induce PHP14 expression in HSCs accompanied with the activation of HSCs. Consistent with the previous study, PHP14 promotes HSCs migration, especially, promotes 3D floating collagen matrices contraction but inhibits stressed-released matrices contraction. Mechanistically, the PI3Kγ/AKT/Rac1 pathway is involved in migration regulated by PHP14. Moreover, PHP14 specifically mediates the TGF-β1 signaling to PI3Kγ/AKT pathway and regulates HSC migration, and thus participates in liver fibrosis. Our study identified the role of PHP14 in liver fibrosis, particularly HSC migration, and suggested a novel mediator of transducting TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway. PHP14 is up-regulated in fibrotic liver and activated hepatic stellate cells. The expression of PHP14 is induced by TGF-β1. The migration of hepatic stellate cells is regulated by PHP14. PHP14 is a mediator of TGF-β1 signaling to PI3Kγ/AKT/Rac1 pathway in hepatic stellate cells.

  12. The effect of down-regulation of Smad3 by RNAi on hepatic stellate cells and a carbon tetrachloride-induced rat model of hepatic fibrosis

    Directory of Open Access Journals (Sweden)

    Z.R. Wang

    2011-02-01

    Full Text Available Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs. The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Colα1, Col3α1, Col4α1, respectively was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30 and the treated group (N = 20 were injected subcutaneously with 40% (v/v carbon tetrachloride (CCl4-olive oil (3 mL/kg, and the normal control group (N = 30 was injected with olive oil (3 mL/kg. In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 µg/kg into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS, and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid. The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05 and the serum indices were greatly improved (P < 0.01. These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.

  13. The CYP2E1 inhibitor DDC up-regulates MMP-1 expression in hepatic stellate cells via an ERK1/2- and Akt-dependent mechanism.

    Science.gov (United States)

    Liu, Tianhui; Wang, Ping; Cong, Min; Xu, Youqing; Jia, Jidong; You, Hong

    2013-06-05

    DDC (diethyldithiocarbamate) could block collagen synthesis in HSC (hepatic stellate cells) through the inhibition of ROS (reactive oxygen species) derived from hepatocyte CYP2E1 (cytochrome P450 2E1). However, the effect of DDC on MMP-1 (matrix metalloproteinase-1), which is the main collagen degrading matrix metalloproteinase, has not been reported. In co-culture experiments, we found that DDC significantly enhanced MMP-1 expression in human HSC (LX-2) that were cultured with hepatocyte C3A cells either expressing or not expressing CYP2E1. The levels of both proenzyme and active MMP-1 enzyme were up-regulated in LX-2 cells, accompanied by elevated enzyme activity of MMP-1 and decreased collagen I, in both LX-2 cells and the culture medium. H2O2 treatment abrogated DDC-induced MMP-1 up-regulation and collagen I decrease, while catalase treatment slightly up-regulated MMP-1 expression. These data suggested that the decrease in ROS by DDC was partially responsible for the MMP-1 up-regulation. ERK1/2 (extracellular signal-regulated kinase 1/2), Akt (protein kinase B) and p38 were significantly activated by DDC. The ERK1/2 inhibitor (U0126) and Akt inhibitor (T3830) abrogated the DDC-induced MMP-1 up-regulation. In addition, a p38 inhibitor (SB203580) improved MMP-1 up-regulation through the stimulation of ERK1/2. Our data indicate that DDC significantly up-regulates the expression of MMP-1 in LX-2 cells which results in greater MMP-1 enzyme activity and decreased collagen I. The enhancement of MMP-1 expression by DDC was associated with H2O2 inhibition and coordinated regulation by the ERK1/2 and Akt pathways. These data provide some new insights into treatment strategies for hepatic fibrosis.

  14. Regulation control and energy management scheme for wireless power transfer

    Science.gov (United States)

    Miller, John M.

    2015-12-29

    Power transfer rate at a charging facility can be maximized by employing a feedback scheme. The state of charge (SOC) and temperature of the regenerative energy storage system (RESS) pack of a vehicle is monitored to determine the load due to the RESS pack. An optimal frequency that cancels the imaginary component of the input impedance for the output signal from a grid converter is calculated from the load of the RESS pack, and a frequency offset f* is made to the nominal frequency f.sub.0 of the grid converter output based on the resonance frequency of a magnetically coupled circuit. The optimal frequency can maximize the efficiency of the power transfer. Further, an optimal grid converter duty ratio d* can be derived from the charge rate of the RESS pack. The grid converter duty ratio d* regulates wireless power transfer (WPT) power level.

  15. The European Energy Regulators Group. A panacea for good governance?

    International Nuclear Information System (INIS)

    Lavrijssen, S.A.C.M.

    2004-01-01

    This article analyses how the European Energy Regulators Group (ERGEG) may promote good governance in the EU. It is concluded that the ERGEG to some extent can stimulate national regulatory authorities into implementing European law more consistently, effectively and proportionally. Since the European Commission has a special responsibility as regards the functioning of the ERGEG, the future role of the ERGEG will depend on whether or not the Commission will leave it some autonomy to develop its advisory-, benchmarking- and coordinating role. Since the European legal framework does not include clear procedural good governance norms, there is a danger that the interests of the market parties are inadequately represented and protected at the European level. Although the ERGEG cannot take legally binding decisions, it is argued that its decisions or common standards may have legal effects. Therefore, it is of the utmost importance that the European legal framework regulates the right of access to ERGEG documents, the exchange and use of information within the ERGEG, the protection of confidential information, the right of participation and the involvement of the European Parliament [nl

  16. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  17. Control of Hepatic Gluconeogenesis by the Promyelocytic Leukemia Zinc Finger Protein

    Science.gov (United States)

    Chen, Siyu; Qian, Jinchun; Shi, Xiaoli; Gao, Tingting; Liang, Tingming

    2014-01-01

    The promyelocytic leukemia zinc finger (PLZF) protein is involved in major biological processes including energy metabolism, although its role remains unknown. In this study, we demonstrated that hepatic PLZF expression was induced in fasted or diabetic mice. PLZF promoted gluconeogenic gene expression and hepatic glucose output, leading to hyperglycemia. In contrast, hepatic PLZF knockdown improved glucose homeostasis in db/db mice. Mechanistically, peroxisome proliferator-activated receptor γ coactivator 1α and the glucocorticoid receptor synergistically activated PLZF expression. We conclude that PLZF is a critical regulator of hepatic gluconeogenesis. PLZF manipulation may benefit the treatment of metabolic diseases associated with gluconeogenesis. PMID:25333514

  18. Advances in ammonia metabolism and hepatic encephalopathy

    International Nuclear Information System (INIS)

    Soeters, P.B.; Wilson, J.H.P.; Meijer, A.J.; Holm, E.

    1988-01-01

    There are four main 'parts' within the book: the first is devoted to peripheral and hepatic ammonia metabolism, the urea cycle, acid base status and its regulation; part two addresses animal models in liver failure, GABA-ergic neurotransmission and its relevance in hepatic failure; a third part concerns neurochemistry including brain ammonia metabolism, serotonin metabolism and energy status, in vivo evaluated with modern techniques like infusion of compounds labeled with stable or radioactive isotopes and with NMR, while the last section provides a description of the determination of ammonia and the treatment of encephalopathy with established but also with experimental techniques. refs.; figs.; tabs

  19. TGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis*

    Science.gov (United States)

    Yadav, Hariom; Devalaraja, Samir; Chung, Stephanie T.; Rane, Sushil G.

    2017-01-01

    Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia and diabetes. Maintenance of glucose homeostasis is achieved via functional interactions among various organs: liver, skeletal muscle, adipose tissue, brain, and the endocrine pancreas. The liver is the primary site of endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D). Thus, elucidating the signaling pathways that regulate hepatic gluconeogenesis would allow better insight into the process of normal endogenous glucose production as well as how this process is impaired in T2D. Here we demonstrate that the TGF-β1/Smad3 signaling pathway promotes hepatic gluconeogenesis, both upon prolonged fasting and during T2D. In contrast, genetic and pharmacological inhibition of TGF-β1/Smad3 signals suppressed endogenous glucose production. TGF-β1 and Smad3 signals achieved this effect via the targeting of key regulators of hepatic gluconeogenesis, protein phosphatase 2A (PP2A), AMP-activated protein kinase (AMPK), and FoxO1 proteins. Specifically, TGF-β1 signaling suppressed the LKB1-AMPK axis, thereby facilitating the nuclear translocation of FoxO1 and activation of key gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. These findings underscore an important role of TGF-β1/Smad3 signaling in hepatic gluconeogenesis, both in normal physiology and in the pathophysiology of metabolic diseases such as diabetes, and are thus of significant medical relevance. PMID:28069811

  20. TGF-β1/Smad3 Pathway Targets PP2A-AMPK-FoxO1 Signaling to Regulate Hepatic Gluconeogenesis.

    Science.gov (United States)

    Yadav, Hariom; Devalaraja, Samir; Chung, Stephanie T; Rane, Sushil G

    2017-02-24

    Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia and diabetes. Maintenance of glucose homeostasis is achieved via functional interactions among various organs: liver, skeletal muscle, adipose tissue, brain, and the endocrine pancreas. The liver is the primary site of endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D). Thus, elucidating the signaling pathways that regulate hepatic gluconeogenesis would allow better insight into the process of normal endogenous glucose production as well as how this process is impaired in T2D. Here we demonstrate that the TGF-β1/Smad3 signaling pathway promotes hepatic gluconeogenesis, both upon prolonged fasting and during T2D. In contrast, genetic and pharmacological inhibition of TGF-β1/Smad3 signals suppressed endogenous glucose production. TGF-β1 and Smad3 signals achieved this effect via the targeting of key regulators of hepatic gluconeogenesis, protein phosphatase 2A (PP2A), AMP-activated protein kinase (AMPK), and FoxO1 proteins. Specifically, TGF-β1 signaling suppressed the LKB1-AMPK axis, thereby facilitating the nuclear translocation of FoxO1 and activation of key gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase. These findings underscore an important role of TGF-β1/Smad3 signaling in hepatic gluconeogenesis, both in normal physiology and in the pathophysiology of metabolic diseases such as diabetes, and are thus of significant medical relevance. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. The European Energy Regulators Group and the realization of the internal energy market

    International Nuclear Information System (INIS)

    Lavrijssen, S.A.C.M.

    2006-01-01

    The role of the European Energy Regulators Group (ERGEG) in the realization of the internal energy market is discussed. It is concluded that the ERGEG has already achieved significant results in dealing with several complex technical and legal problems that hamper market integration in the energy sector. However, it is a fundamental problem that the ERGEG is neither an EU institution nor a national institution, resulting in a lack of its democratic accountability and in the legal protection against the actions taken by the ERGEG. Therefore, the future success of the ERGEG will depend on the ability of the European legislator to find answers to the question how to ensure that the ERGEG fulfils its tasks in a legitimate way [nl

  2. A high protein diet during pregnancy affects hepatic gene expression of energy sensing pathways along ontogenesis in a porcine model.

    Directory of Open Access Journals (Sweden)

    Michael Oster

    Full Text Available In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP or an adequate protein diet (AP, 12% CP throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc and postnatal stages (1, 28, 188 dpn. Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages.

  3. Government regulation as an impetus for innovation: Evidence from energy performance regulation in the Dutch residential building sector

    International Nuclear Information System (INIS)

    Beerepoot, Milou; Beerepoot, Niels

    2007-01-01

    The recent implementation of energy performance policy as a way to tackle energy consumption in the building sector in Europe draws attention to the effect it has on the development and diffusion of energy-saving innovations. According to innovation system literature, government regulation through norms and standards is one of the factors stimulating innovation. This paper concentrates on the role of stricter government regulation as an incentive to innovation in the Dutch residential building sector. Innovation in this sector is predominantly a process of applying incremental modifications to comply with new and stricter government regulations and standards. Energy performance policy in its current shape will therefore not contribute to the diffusion of really new innovation in energy techniques for residential buildings in the Netherlands. If diffusion of really new innovation is an explicit aim of energy performance policy then the European wide introduction of this scheme needs reconsideration

  4. FoxO1 and HNF-4 are involved in regulation of hepatic glucokinase gene expression by resveratrol.

    Science.gov (United States)

    Ganjam, Goutham Kumar; Dimova, Elitsa Y; Unterman, Terry G; Kietzmann, Thomas

    2009-11-06

    Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol.

  5. FoxO1 and HNF-4 Are Involved in Regulation of Hepatic Glucokinase Gene Expression by Resveratrol*

    Science.gov (United States)

    Ganjam, Goutham Kumar; Dimova, Elitsa Y.; Unterman, Terry G.; Kietzmann, Thomas

    2009-01-01

    Resveratrol, a polyphenol derived from grapes, exerts important effects on glucose and lipid metabolism, yet detailed mechanisms mediating these effects remain unknown. The liver plays a central role in energy homeostasis, and glucokinase (GK) is a key enzyme involved in glucose utilization. Resveratrol activates SIRT1 (sirtuin 1), which promotes deacetylation of the forkhead transcription factor FoxO1. Previously, we reported that FoxO1 can suppress and that HNF-4 can stimulate GK expression in the liver. Here, we examined the role of FoxO1 and HNF-4 in mediating resveratrol effects on liver GK expression. Resveratrol suppressed hepatic GK expression in vivo and in isolated hepatocytes, and knocking down FoxO1 with shRNAs disrupted this effect. Reporter gene, gel shift, supershift assay, and chromatin immunoprecipitation studies show that FoxO1 binds to the GK promoter and that the interplay between FoxO1 and HNF-4 within the GK promoter is essential for mediating the effects of resveratrol. Resveratrol promotes deacetylation of FoxO1 and enhances its recruitment to the FoxO-binding element. Conversely, resveratrol suppresses recruitment of HNF-4 to its binding site, and knockdown of FoxO1 blocks this effect of resveratrol. Coprecipitation and chromatin immunoprecipitation studies show that resveratrol enhances interaction between FoxO1 and HNF-4, reduces binding of HNF-4 to its own site, and promotes its recruitment to the FoxO site in a FoxO1-dependent manner. These results provide the first evidence that resveratrol represses GK expression via FoxO1 and that the interaction between FoxO1 and HNF-4 contributes to these effects of resveratrol. PMID:19740748

  6. Challenges of atomic energy regulation in Indian context

    International Nuclear Information System (INIS)

    Bajaj, S.S.

    2010-01-01

    Over the years, India has mastered all the stages of the nuclear fuel cycle, which include mining, processing and fabrication of nuclear fuel; design, construction, and operation of nuclear power reactors and research reactors; reprocessing of spent fuel and management of radioactive wastes. Ionising radiation is also used widely in medical, industrial and research areas. Since its inception, Department of Atomic Energy (DAE) was enforcing radiological safety in the country through in-house or ad-hoc committees, till a dedicated regulatory body (AERB) was set up 25 years ago. Today India is operating 19 nuclear power plants with different vintages (2 BWRs and 17 PHWRs) and another 8 (1 PFBR, 5 PHWRs and 2 PWRs) are in various stages of construction. Recently there are new evolutionary reactors (AHWRs) for which design has been completed and are on the threshold for consideration for construction. To match the rapid growth in the need for power India is also about to take up construction of large evolutionary PWRs of foreign design. This variety in the Indian nuclear power programme has come up due to a systematic evaluation and optimisation of the resources and technology available within the country. Added to this is the growing use of radiation in non-power applications. As the safety supervision of this huge programme is the responsibility of AERB, it faces various challenges, like, - Strategies for regulating wide variety of nuclear and radiation facilities with wide dispersal; - Meeting present day expectations with regard to nuclear and radiation safety and nuclear security; - The safety and security of large number of radioactive sources spread over such a vast country and of the associated import/export guidance; - Ensuring safety of old plants by periodic reviews and by prescribing adequate safety upgradation and ageing management programme; -Adaptation of the regulatory system and of regulations to new and foreign design nuclear technologies and

  7. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... 1 (von Gierke) Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Intrahepatic Cholestasis of Pregnancy (ICP) Jaundice ... diseases. What are the common causes of cirrhosis? Hepatitis B & C Alcohol-related Liver Disease Non-alcoholic Fatty ...

  8. An energy-efficient, adiabatic electrode stimulator with inductive energy recycling and feedback current regulation.

    Science.gov (United States)

    Arfin, Scott K; Sarpeshkar, Rahul

    2012-02-01

    In this paper, we present a novel energy-efficient electrode stimulator. Our stimulator uses inductive storage and recycling of energy in a dynamic power supply. This supply drives an electrode in an adiabatic fashion such that energy consumption is minimized. It also utilizes a shunt current-sensor to monitor and regulate the current through the electrode via feedback, thus enabling flexible and safe stimulation. Since there are no explicit current sources or current limiters, wasteful energy dissipation across such elements is naturally avoided. The dynamic power supply allows efficient transfer of energy both to and from the electrode and is based on a DC-DC converter topology that we use in a bidirectional fashion in forward-buck or reverse-boost modes. In an exemplary electrode implementation intended for neural stimulation, we show how the stimulator combines the efficiency of voltage control and the safety and accuracy of current control in a single low-power integrated-circuit built in a standard .35 μm CMOS process. This stimulator achieves a 2x-3x reduction in energy consumption as compared to a conventional current-source-based stimulator operating from a fixed power supply. We perform a theoretical analysis of the energy efficiency that is in accord with experimental measurements. This theoretical analysis reveals that further improvements in energy efficiency may be achievable with better implementations in the future. Our electrode stimulator could be widely useful for neural, cardiac, retinal, cochlear, muscular and other biomedical implants where low power operation is important.

  9. Parental influences on children's self-regulation of energy intake: Insights from developmental literature on emotion regulation

    Science.gov (United States)

    This article examines the role of parents in the development of children's self-regulation of energy intake. Various paths of parental influence are offered based on the literature on parental influences on children's emotion self-regulation. The parental paths include modeling, responses to childre...

  10. Effects of short-term high-fat, high-energy diet on hepatic and myocardial triglyceride content in healthy men

    NARCIS (Netherlands)

    van der Meer, Rutger W.; Hammer, Sebastiaan; Lamb, Hildo J.; Frölich, Marijke; Diamant, Michaela; Rijzewijk, Luuk J.; de Roos, Albert; Romijn, Johannes A.; Smit, Johannes W. A.

    2008-01-01

    An association has been suggested between elevated plasma nonesterified fatty acid (NEFA) levels, myocardial triglyceride (TG) accumulation, and myocardial function. Our objective was to investigate the effects of an elevation of plasma NEFA by a high-fat, high-energy (HFHE) diet on hepatic and

  11. Autoimmune hepatitis.

    Science.gov (United States)

    Vergani, D; Mieli-Vergani, G

    2004-06-01

    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  12. The relationship between house size and life cycle energy demand: Implications for energy efficiency regulations for buildings

    International Nuclear Information System (INIS)

    Stephan, André; Crawford, Robert H.

    2016-01-01

    House size has significantly increased over the recent decades in many countries. Larger houses often have a higher life cycle energy demand due to their increased use of materials and larger area to heat, cool and light. Yet, most energy efficiency regulations for buildings fail to adequately include requirements for addressing the energy demand associated with house size. This study quantifies the effect of house size on life cycle energy demand in order to inform future regulations. It uses a parametric model of a typical detached house in Melbourne, Australia and varies its floor area from 100 to 392 m"2 for four different household sizes. Both initial and recurrent embodied energy requirements are quantified using input-output-based hybrid analysis and operational energy is calculated in primary energy terms over 50 years. Results show that the life cycle energy demand increases at a slower rate compared to house size. Expressing energy efficiency per m"2 therefore favours large houses while these require more energy. Also, embodied energy represents 26–50% across all variations. Building energy efficiency regulations should incorporate embodied energy, correct energy intensity thresholds for house size and use multiple functional units to measure efficiency. These measures may help achieve greater net energy reductions. - Highlights: • The life cycle energy demand (LCE) is calculated for 90 house sizes and 4 household sizes. • The LCE is sublinearly correlated with house size. • Larger houses appear to be more energy efficient per m"2 while they use more energy overall. • Embodied energy (EE) represents up to 52% of the LCE over 50 years. • Building energy efficiency regulations need to consider house size and EE.

  13. Hepatitis Vaccines

    OpenAIRE

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  14. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Donate Today Enroll in 123 What is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy or PSE, is a condition that causes temporary ...

  15. Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation

    DEFF Research Database (Denmark)

    Pham, Long; Ngo, HT; Lim, YS

    2012-01-01

    Background & Aims Hepatitis C virus (HCV) requires host cellular proteins for its own propagation. To identify the cellular factors necessary for HCV propagation, we have recently screened the small interfering RNA (siRNA) library targeting cell cycle genes using cell culture grown HCV (HCVcc...

  16. End users heat energy savings using thermostat regulation valves radiators, v. 16(64)

    International Nuclear Information System (INIS)

    Jakimovska, Emilija Misheva; Potsev, Eftim

    2008-01-01

    Billing the used heat energy offers the opportunity to motivate end users to use the heat energy rationally and to save the energy. Installing the thermostat valves on the radiators it is possible frequently to regulate the room temperature and to use the heat gains, obtaining comfortable climate in the apartments and saving the energy. Thermostat valves give the possibility to use the heat energy rationally and save the energy, and these way and users can regulate the heat energy consumption according to their own level of thermal comfort. (Author)

  17. End users heat energy savings using thermostat regulation valves radiators, v. 16(63)

    International Nuclear Information System (INIS)

    Jakimovska, Emilija Misheva; Potsev, Eftim

    2008-01-01

    Billing the used heat energy offers the opportunity to motivate end users to use the heat energy rationally and to save the energy. Installing the thermostat valves on the radiators it is possible frequently to regulate the room temperature and to use the heat gains, obtaining comfortable climate in the apartments and saving the energy. Thermostat valves give the possibility to use the heat energy rationally and save the energy, and these way and users can regulate the heat energy consumption according to their own level of thermal comfort. (Author)

  18. A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD.

    Directory of Open Access Journals (Sweden)

    William B Ashworth

    2016-09-01

    Full Text Available In non-alcoholic fatty liver disease (NAFLD, lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation

  19. A Computational Model of Hepatic Energy Metabolism: Understanding Zonated Damage and Steatosis in NAFLD

    Science.gov (United States)

    Ashworth, William B.; Bogle, I. David L.

    2016-01-01

    In non-alcoholic fatty liver disease (NAFLD), lipid build-up and the resulting damage is known to occur more severely in pericentral cells. Due to the complexity of studying individual regions of the sinusoid, the causes of this zone specificity and its implications on treatment are largely ignored. In this study, a computational model of liver glucose and lipid metabolism is presented which treats the sinusoid as the repeating unit of the liver rather than the single hepatocyte. This allows for inclusion of zonated enzyme expression by splitting the sinusoid into periportal to pericentral compartments. By simulating insulin resistance (IR) and high intake diets leading to the development of steatosis in the model, we identify key differences between periportal and pericentral cells accounting for higher susceptibility to pericentral steatosis. Secondly, variation between individuals is seen in both susceptibility to steatosis and in its development across the sinusoid. Around 25% of obese individuals do not show excess liver fat, whilst 16% of lean individuals develop NAFLD. Furthermore, whilst pericentral cells tend to show higher lipid levels, variation is seen in the predominant location of steatosis from pericentral to pan-sinusoidal or azonal. Sensitivity analysis was used to identify the processes which have the largest effect on both total hepatic triglyceride levels and on the sinusoidal location of steatosis. As is seen in vivo, steatosis occurs when simulating IR in the model, predominantly due to increased uptake, along with an increase in de novo lipogenesis. Additionally, concentrations of glucose intermediates including glycerol-3-phosphate increased when simulating IR due to inhibited glycogen synthesis. Several differences between zones contributed to a higher susceptibility to steatosis in pericentral cells in the model simulations. Firstly, the periportal zonation of both glycogen synthase and the oxidative phosphorylation enzymes meant that the

  20. Single-energy non-contrast hepatic steatosis criteria applied to virtual non-contrast images: is it still highly specific and positively predictive?

    Science.gov (United States)

    Haji-Momenian, S; Parkinson, W; Khati, N; Brindle, K; Earls, J; Zeman, R K

    2018-06-01

    To determine the sensitivity, specificity, and predictive values of single-energy non-contrast hepatic steatosis criteria on dual-energy virtual non-contrast (VNC) images. Forty-eight computed tomography (CT) examinations, which included single-energy non-contrast (TNC) and contrast-enhanced dual-energy CT angiography (CTA) of the abdomen, were enrolled. VNC images were reconstructed from the CTA. Region of interest (ROI) attenuations were measured in the right and left hepatic lobes, spleen, and aorta on TNC and VNC images. The right and left hepatic lobes were treated as separate samples. Steatosis was diagnosed based on TNC liver attenuation of ≤40 HU or liver attenuation index (LAI) of ≤-10 HU, which are extremely specific and predictive for moderate to severe steatosis. The sensitivity, specificity, and predictive values of VNC images for steatosis were calculated. VNC-TNC deviations were correlated with aortic enhancement and patient water equivalent diameter (PWED). Thirty-two liver ROIs met steatosis criteria based on TNC attenuation; VNC attenuation had sensitivity, specificity, and a positive predictive value of 66.7%, 100%, and 100%, respectively. Twenty-one liver ROIs met steatosis criteria based on TNC LAI. VNC LAI had sensitivity, specificity, and positive predictive values of 61.9%, 90.7%, and 65%, respectively. Hepatic and splenic VNC-TNC deviations did not correlate with one another (R 2 =0.08), aortic enhancement (R 2 predictive for moderate to severe steatosis on VNC reconstructions from the arterial phase. Hepatic attenuation performs better than LAI criteria. VNC deviations are independent of aortic enhancement and PWED. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  1. miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

    Science.gov (United States)

    Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

    2017-10-31

    A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

  2. Hypodense liver lesions in patients with hepatic steatosis: do we profit from dual-energy computed tomography?

    Energy Technology Data Exchange (ETDEWEB)

    Nattenmueller, Johanna; Hosch, Waldemar; Nguyen, Tri-Thien; Skornitzke, Stephan; Joeres, Andreas; Grenacher, Lars; Kauczor, Hans-Ulrich; Sommer, Christof M.; Stiller, Wolfram [University Hospital Heidelberg, Department of Diagnostic and Interventional Radiology (DIR), Heidelberg (Germany)

    2015-12-15

    To evaluate dual-energy CT (DECT) imaging of hypodense liver lesions in patients with hepatic steatosis, having a high incidence in the general population and among cancer patients receiving chemotherapy. One hundred and five patients with hepatic steatosis (liver parenchyma <40 HU) underwent contrast-enhanced DECT with reconstruction of pure iodine (PI), optimum contrast (OC), 80 kV{sub p}, and 120 kV{sub p}-equivalent data sets. Image noise (IN), lesion to liver signal to noise (SNR) and contrast to noise (CNR) ratios were quantitatively analysed; image quality was rated on a 5-point scale (1, excellent; 2, good; 3, fair; 4, poor; 5, non-diagnostic) by two independent reviewers. In 21 patients with hypodense liver lesions, IN was lowest in PI followed by 120 kV{sub p}-equivalent and OC, and highest in 80 kV{sub p}. SNR was highest in PI (1.30), followed by 120 kV{sub p}-equivalent (0.72) and 80 kV{sub p} (0.63), and lowest in OC (0.55). CNR was highest in 120 kV{sub p}-equivalent (4.95), followed by OC (4.55) and 80 kV{sub p} (4.14), and lowest in PI (3.63). The 120 kV{sub p}-equivalent series exhibited best overall qualitative image score (1.88), followed by OC (1.98), 80 kV{sub p} (3.00) and PI (3.67). In our study, the 120 kV{sub p}-equivalent series was best suited for visualization of hypodense lesions within steatotic liver parenchyma, while using DECT currently seems to offer no additional diagnostic advantage. (orig.)

  3. Improvement and rationalization of nuclear energy laws and regulations

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chum; Kim, Hak Man; Oh, Ho Chul [Chongju Univ., Cheongju (Korea, Republic of)

    2002-03-15

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.

  4. Improvement and rationalization of nuclear energy laws and regulations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mo Sung; Chung, Gum Chun; Kim, Hak Man; Oh, Ho Chul [Cheongju Univ., Cheongju (Korea, Republic of)

    2001-03-15

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea.

  5. Improvement and rationalization of nuclear energy laws and regulations

    International Nuclear Information System (INIS)

    Cho, Byung Sun; Lee, Mo Sung; Chung, Gum Chum; Kim, Hak Man; Oh, Ho Chul

    2002-03-01

    Since the present legal system on nuclear safety regulation has some problems that refer to contents of regulatory provisions, this mid-report has preformed research on the legal basic theory of nuclear safety regulation. And then secondly this report analyzed the problems of each provisions and suggested the revision drafts on the basis of analyzing problems and the undergoing theory of nuclear safety regulation. In order to interpret easily this report finally took the cases of judicial precedents on nuclear safety regulation in USA, Germany, Japan and Korea

  6. The role of chicken ovalbumin upstream promoter transcription factor II in the regulation of hepatic fatty acid oxidation and gluconeogenesis in newborn mice.

    Science.gov (United States)

    Planchais, Julien; Boutant, Marie; Fauveau, Véronique; Qing, Lou Dan; Sabra-Makke, Lina; Bossard, Pascale; Vasseur-Cognet, Mireille; Pégorier, Jean-Paul

    2015-05-15

    Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an orphan nuclear receptor involved in the control of numerous functions in various organs (organogenesis, differentiation, metabolic homeostasis, etc.). The aim of the present work was to characterize the regulation and contribution of COUP-TFII in the control of hepatic fatty acid and glucose metabolisms in newborn mice. Our data show that postnatal increase in COUP-TFII mRNA levels is enhanced by glucagon (via cAMP) and PPARα. To characterize COUP-TFII function in the liver of suckling mice, we used a functional (dominant negative form; COUP-TFII-DN) and a genetic (shRNA) approach. Adenoviral COUP-TFII-DN injection induces a profound hypoglycemia due to the inhibition of gluconeogenesis and fatty acid oxidation secondarily to reduced PEPCK, Gl-6-Pase, CPT I, and mHMG-CoA synthase gene expression. Using the crossover plot technique, we show that gluconeogenesis is inhibited at two different levels: 1) pyruvate carboxylation and 2) trioses phosphate synthesis. This could result from a decreased availability in fatty acid oxidation arising cofactors such as acetyl-CoA and reduced equivalents. Similar results are observed using the shRNA approach. Indeed, when fatty acid oxidation is rescued in response to Wy-14643-induced PPARα target genes (CPT I and mHMG-CoA synthase), blood glucose is normalized in COUP-TFII-DN mice. In conclusion, this work demonstrates that postnatal increase in hepatic COUP-TFII gene expression is involved in the regulation of liver fatty acid oxidation, which in turn sustains an active hepatic gluconeogenesis that is essential to maintain an appropriate blood glucose level required for newborn mice survival. Copyright © 2015 the American Physiological Society.

  7. Hepatitis B virus enhances cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 Kda.

    Science.gov (United States)

    Zhang, Xiaoxue; Zhang, Rui; Yang, HuiOu; Xiang, Qian; Jiang, Qing; He, Qi; Zhang, Ting; Chen, Chen; Zhu, Huifen; Wang, Qiang; Ning, Qin; Li, Yiwu; Lei, Ping; Shen, Guanxin

    2016-07-25

    Cisplatin is a classical platinum-based chemotherapeutic drug used in the treatment of many cancer types, including hepatocellular carcinoma (HCC). The application of cisplatin is significantly limited by its toxicity, which may be affected by various biological factors. Persistence of Hepatitis B virus (HBV) infection leads to HCC development and may be associated with higher incidence of severe hepatitis during chemotherapy. However, whether HBV alters the susceptibility of hepatocytes to cisplatin remains poorly understood. Here, we demonstrate that HBV transfection enhanced cisplatin-induced hepatotoxicity via a mechanism involving suppression of glucose-regulated protein of 78 KDa (Grp78), a major stress-induced chaperone that localizes to the endoplasmic reticulum. Silencing Grp78 gene increased the susceptibility of HepG2 to cisplatin by activating caspase-3. Grp78 expression was down-regulated by HBV infection both in vitro and in liver tissues of patients. We compared the cisplatin sensitivity of hepatoma cells either expressing (HepG2.2.15 cells) or not expressing the entire Hepatitis B Virus genome (HepG2). HepG2.2.15 cells showed increased sensitivity to cisplatin and a higher apoptosis rate. Overexpression of Grp78 counteracted the increase of sensitivity of HepG2.215 cells to cisplatin. Furthermore, we found that HBV disrupted Grp78 synthesis in response to cisplatin stimulation, which may trigger severe and prolonged endoplasmic reticulum (ER) stress that can induce cellular apoptosis. Our findings provide new information into the effect of HBV in the modulation of Grp78 expression, and, consequently on cisplatin-induced hepatotoxicity during viral infection. Copyright © 2016. Published by Elsevier Ireland Ltd.

  8. Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats.

    Science.gov (United States)

    Ding, Shibin; Jiang, Jinjin; Zhang, Guofu; Bu, Yongjun; Zhang, Guanghui; Zhao, Xiangmei

    2017-01-01

    Studies have demonstrated that resveratrol (a natural polyphenol) and caloric restriction activate Sirtuin-1 (SIRT1) and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD) development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy. Eight-week-old male Wistar rats (40) were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw); and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER) stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw) and caloric restriction (30%) partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight. We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30%) and resveratrol (a pharmacological SIRT1 activator) supplementation

  9. Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats.

    Directory of Open Access Journals (Sweden)

    Shibin Ding

    Full Text Available Studies have demonstrated that resveratrol (a natural polyphenol and caloric restriction activate Sirtuin-1 (SIRT1 and induce autophagy. Furthermore, autophagy is induced by the SIRT1-FoxO signaling pathway and was recently shown to be a critical protective mechanism against non-alcoholic fatty liver disease (NAFLD development. We aimed to compare the effects of resveratrol and caloric restriction on hepatic lipid metabolism and elucidate the mechanism by which resveratrol supplementation and caloric restriction alleviate hepatosteatosis by examining the molecular interplay between SIRT1 and autophagy.Eight-week-old male Wistar rats (40 were divided into four groups: the STD group, which was fed a standard chow diet; the HFD group, which was fed a high-fat diet; HFD-RES group, which was fed a high-fat diet plus resveratrol (200 mg/kg.bw; and the HFD-CR group, which was fed a high-fat diet in portions containing 70% of the mean intake of the HFD group rats. The groups were maintained for 18 weeks. Metabolic parameters, Oil Red O and hematoxylin-eosin staining of the liver, and the mRNA and protein expression of SIRT1, autophagy markers and endoplasmic reticulum(ER stress-associated genes in the liver were assessed after the 18-week treatment. We found that resveratrol (200 mg/kg bw and caloric restriction (30% partially prevented hepatic steatosis and hepatocyte ballooning, increased the expression of SIRT1 and autophagy markers while decreasing ER stress markers in the liver and alleviated lipid metabolism disorder. Moreover, caloric restriction provided superior protection against HFD-induced hepatic fatty accumulation compared with resveratrol and the effects were associated with decreased total energy intake and body weight.We conclude that the SIRT1-autophagy pathway and decreased ER stress are universally required for the protective effects of moderate caloric restriction (30% and resveratrol (a pharmacological SIRT1 activator

  10. Low energy class 1 typehouses according to the Danish building regulations

    DEFF Research Database (Denmark)

    Rose, Jørgen; Kragh, Jesper; Svendsen, Svend

    2008-01-01

    In 2005 the Danish Building regulations introduced two low energy classes for buildings in addition to tightened minimum requirements. The low energy class 1 and low energy class 2 correspond to total energy use, i.e. energy use for heating, ventilation, cooling and domestic hot water, as 50......% and 75% of the minimum requirement respectively. The main purpose of introducing the low energy classes were to further support and encourage the development of low energy buildings in Denmark. In 2010 it is expected that demands in the Building Regulations are tightened by 25-30% and in 2015...... it is expected that the minimum demand will correspond to the low energy class 1 demands of today. In order to secure this development in the building regulations, it is essential to support the development of low energy solutions and demonstrate that the goal is well within reach of the Danish building industry...

  11. Effect of moderate dietary restriction on visceral organ weight, hepatic oxygen consumption, and metabolic proteins associated with energy balance in mature pregnant beef cows.

    Science.gov (United States)

    Wood, K M; Awda, B J; Fitzsimmons, C; Miller, S P; McBride, B W; Swanson, K C

    2013-09-01

    Twenty-two nonlactating multiparous pregnant beef cows (639 ± 68 kg) were used to investigate the effect of dietary restriction on the abundance of selected proteins regulating cellular energy metabolism. Cows were fed at either 85% (n = 11; LOW) or 140% (n = 11; HIGH) of total NE requirements. The diet consisted of a haylage-based total mixed ration containing 20% wheat straw. Cows were slaughtered by block (predicted date of parturition), beginning 83 d after the initiation of dietary treatments and every week thereafter for 6 wk, such that each block was slaughtered at approximately 250 d of gestation. Tissue samples from liver, kidney, sternomandibularis muscle, ruminal papilli (ventral sac), pancreas, and small intestinal muscosa were collected at slaughter and snap frozen in liquid N2. Western blots were conducted to quantify abundance of proliferating cell nuclear antigen (PCNA), ATP synthase, ubiquitin, and Na/K+ ATPase for all tissues; PPARγ, PPARγ coactivator 1 α (PGC-1α), and 5´-adenosine monophosphate-activated protein kinase (AMPK) and the activated form phosphorylated-AMPK (pAMPK) for liver, muscle, and rumen; phosphoenolpyruvate carboxykinase (PEPCK) for liver and kidney; and uncoupling protein 2 (UCP2) for liver. Statistical analysis was conducted using Proc Mixed in SAS and included the fixed effects of dietary treatment, cow age, block, and the random effect of pen. Dietary treatments resulted in cows fed HIGH having greater (P ≤ 0.04) ADG and final BW than cows fed LOW. Abundance of ubiquitin in muscle was greater (P = 0.009) in cows fed LOW, and PCG-1 α in liver was greater (P = 0.03) in cows fed HIGH. Hepatic O2 consumption was greater in HIGH (P ≤ 0.04). Feed intake can influence the abundance of important metabolic proteins and suggest that protein degradation may increase in muscle from moderately nutrient restricted cows and that energy metabolism in liver increases in cows fed above NE requirements.

  12. Inside the black box: incentive regulation and incentive channeling on energy markets

    NARCIS (Netherlands)

    K. Heine (Klaus)

    2013-01-01

    textabstractThis paper aims to achieve more insight into the complex interplay between the "external" market regulations and "internal" regulations (corporate governance) of energy firms. In recent years, many countries have deregulated the incumbent energy monopolies and have introduced new modes

  13. PGC-1alpha Deficiency Causes Multi-System Energy Metabolic Derangements: Muscle Dysfunction, Abnormal Weight Control and Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Leone Teresa C

    2005-01-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha-/- mice. With age, the PGC-1alpha-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  14. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis.

    Directory of Open Access Journals (Sweden)

    Teresa C Leone

    2005-04-01

    Full Text Available The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha was targeted in mice. PGC-1alpha null (PGC-1alpha(-/- mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. The postnatal growth of heart and slow-twitch skeletal muscle, organs with high mitochondrial energy demands, is blunted in PGC-1alpha(-/- mice. With age, the PGC-1alpha(-/- mice develop abnormally increased body fat, a phenotype that is more severe in females. Mitochondrial number and respiratory capacity is diminished in slow-twitch skeletal muscle of PGC-1alpha(-/- mice, leading to reduced muscle performance and exercise capacity. PGC-1alpha(-/- mice exhibit a modest diminution in cardiac function related largely to abnormal control of heart rate. The PGC-1alpha(-/- mice were unable to maintain core body temperature following exposure to cold, consistent with an altered thermogenic response. Following short-term starvation, PGC-1alpha(-/- mice develop hepatic steatosis due to a combination of reduced mitochondrial respiratory capacity and an increased expression of lipogenic genes. Surprisingly, PGC-1alpha(-/- mice were less susceptible to diet-induced insulin resistance than wild-type controls. Lastly, vacuolar lesions were detected in the central nervous system of PGC-1alpha(-/- mice. These results demonstrate that PGC-1alpha is necessary for appropriate adaptation to the metabolic and physiologic stressors of postnatal life.

  15. An evolutionary triple helix to strengthen energy regulation: Implications for management

    Energy Technology Data Exchange (ETDEWEB)

    Rizzi, Francesco; Borzoni, Matteo

    2010-09-15

    Regulation is the basic tool to implement energy policy. The evolution of the regulation is influenced by its impacts on the industrial activities. Consequently, entrepreneurs acts in a continuously adapting-by-interacting environment. Both from a systemic and an atomistic perspective, this paper provides a theoretical framework for energy regulation development in order to support management implications. This work builds on the triple helix model and extends it to energy regulation development processes. It concludes that the analysis of intangible resources and their related services at inter-organizational level is fundamental to guide companies in designing win-win corporate strategies and in their operazionalization.

  16. Atomic Energy Control Regulations: interpretation of revisions relating to industrial radiography

    International Nuclear Information System (INIS)

    1983-09-01

    The purpose of this document is to provide assistance to those affected by section 18 to 18.23 of the Canadian Atomic Energy Control Regulations. Words, phrases, and concepts that are specific to these Regulations are explained herein. However, the corresponding sections of the Regulations should be examined to obtain the exact wording. Although sections 18 to 18.23 of the Canadian Atomic Energy Control Regulations apply to both neutron and gamma radiography, this guide has been written for only the latter. Persons engaged in neutron radiography should consult the Atomic Energy Control Board (AECB)

  17. Hepatitis C: Managing Pain

    Science.gov (United States)

    ... Pain: Entire Lesson Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans and the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting ...

  18. Proceedings of the 8. Brazilian congress on energy: energy policy, regulation and sustainable development. v. 3: technological innovation, renewable sources and rural energization

    International Nuclear Information System (INIS)

    1999-01-01

    These proceedings cover the papers presented in the 8. Brazilian congress on energy held at Rio de Janeiro from November, 30 to December, 02, 1999, focusing energy policy, regulation and sustainable development, specifically the contribution of energy to a satisfactory quality of life for everyone. Within such a context, the congress technical programme has been structured around six different divisions: energy, environment and development; energy sector regulation; energy policy and planning; technology innovation; energy conservation; renewable energy sources and rural areas energy supply

  19. Viability of using energy storage for frequency regulation on power grid

    Science.gov (United States)

    Lim, Y. S.; Hau, L. C.; Loh, K. Y.; Lim, K. Y.; Lyons, P. F.; Taylor, P. C.

    2018-05-01

    This project is about the development and integration of a real-time network simulator in the laboratory using hardware in the loop (HIL) for the purpose of frequency regulation. Frequency regulation is done using the energy storage system (ESS) and a real-time network test bed developed in the smart energy laboratory in Newcastle University. An IEEE Test System was built in the OPAL-RT network simulator to mimic the power grid with renewable energy sources. The study demonstrates the viability of using an ESS to regulate the frequency under an increased penetration of renewable energy sources.

  20. Energy regulation in China: Objective selection, potential assessment and responsibility sharing by partial frontier analysis

    International Nuclear Information System (INIS)

    Xia, X.H.; Chen, Y.B.; Li, J.S.; Tasawar, H.; Alsaedi, A.; Chen, G.Q.

    2014-01-01

    To cope with the excessive growth of energy consumption, the Chinese government has been trying to strengthen the energy regulation system by introducing new initiatives that aim at controlling the total amount of energy consumption. A partial frontier analysis is performed in this paper to make a comparative assessment of the combinations of possible energy conservation objectives, new constraints and regulation strategies. According to the characteristics of the coordination of existing regulation structure and the optimality of regulation strategy, four scenarios are constructed and regional responsibilities are reasonably divided by fully considering the production technology in the economy. The relative importance of output objectives and the total amount controlling is compared and the impacts on the regional economy caused by the changes of regulation strategy are also evaluated for updating regulation policy. - Highlights: • New initiatives to control the total amount of energy consumption are evaluated. • Twenty-four regulation strategies and four scenarios are designed and compared. • Crucial regions for each sector and regional potential are identified. • The national goals of energy abatement are decomposed into regional responsibilities. • The changes of regulation strategy are evaluated for updating regulation policy

  1. Regulating nuclear energy in a time of change

    International Nuclear Information System (INIS)

    Alonso, A.

    2000-01-01

    This presentation deals mainly with the relationship between regulators and licensees and on the ways and means the benefits of degradation and competitiveness could be realized without impairing safety beyond the acceptable limits

  2. Scenarios for a urban energy transition. Actors, regulations, technologies

    International Nuclear Information System (INIS)

    Debizet, Gilles; Blanco, Sylvie; Buclet, Nicolas; Forest, Fabrice; Gauthier, Caroline; La Branche, Stephane; Menanteau, Philippe; Schneuwly, Patrice; Tabourdeau, Antoine

    2016-01-01

    Cities concentrate populations, consumptions, levers of actions, and are places of various experiments for energy transition. This book aims at giving an overview of possible scenarios of development of renewable energies in urban context. It is based on interviews of actors of the energy, building and urban planning sectors by researchers in town planning, management, technology, political and economic sciences. The authors examine what would occur if large companies would manage entire quarters, if local authorities would supervise production and supply, if the State would take control of all fields of action again, or if consumer cooperatives would exchange energy and pool productions. In its different chapters, the book presents four scenarios of energy coordination in urban context by 2040, discuss energy transition in urban spaces, discuss the perspectives of evolution towards more autonomous cities and quarters from an energetic point of view, and discuss business models and urban energetic innovations

  3. Variable liver fat concentration as a proxy for body fat mobilization postpartum has minor effects on insulin-induced changes in hepatic gene expression related to energy metabolism in dairy cows.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Bruckmaier, R M; Röntgen, M; Kuhla, B; Hammon, H M

    2017-02-01

    The liver plays a central role in adaptation for energy requirements around calving, and changes in the effects of insulin on hepatic energy metabolism contribute to metabolic adaptation in dairy cows. Hepatic insulin effects may depend on body fat mobilization. The objective of this study was to investigate the effects of insulin on the hepatic gene expression of enzymes involved in energy metabolism and factors related to nutrition partitioning in cows with high and low total liver fat concentration (LFC) after calving. Holstein cows were retrospectively grouped according to their LFC after calving as a proxy for body fat mobilization. Cows were classified as low (LLFC; LFC 24.4% fat/dry matter; n = 10) fat-mobilizing after calving. Euglycemic-hyperinsulinemic clamps [6 mU/(kg × min) of insulin for 6 h] were performed in wk 5 antepartum (ap) and wk 3 postpartum (pp). Before and at the end of the euglycemic-hyperinsulinemic clamps, liver biopsies were taken to measure the mRNA abundance of enzymes involved in carbohydrate and lipid metabolism, expression related to the somatotropic axis, and adrenergic and glucocorticoid receptors. The mRNA abundance of pyruvate carboxylase, cytosolic phosphoenolpyruvate carboxykinase (PEPCK; PCK1), acyl-CoA-dehydrogenase very long chain (ACADVL), and hydroxyl-methyl-glutaryl-CoA-synthase 1 increased, but the mRNA abundance of solute carrier family 2 (SLC2A2 and SLC2A4), growth hormone receptor 1A (GHR1A), insulin-like growth factor 1 (IGF1), sterol regulatory element binding factor 1, adrenoceptor α 1A, and glucocorticoid receptor decreased from ap to pp. Insulin treatment was associated with decreased PCK1, mitochondrial PEPCK, glucose-6-phosphatase, propionyl-CoA-carboxylase α, carnitine-palmitoyl-transferase 1A, ACADVL, and insulin receptor mRNA, but increased IGF1 and SLC2A4 mRNA ap and pp and GHR1A mRNA pp. The mRNA abundance of SLC2A4 was greater, and the mRNA abundance of GHR1A and IGF1 tended to be lower in LLFC than

  4. The Hepatitis C Virus-induced NLRP3 Inflammasome Activates the Sterol Regulatory Element-binding Protein (SREBP) and Regulates Lipid Metabolism.

    Science.gov (United States)

    McRae, Steven; Iqbal, Jawed; Sarkar-Dutta, Mehuli; Lane, Samantha; Nagaraj, Abhiram; Ali, Naushad; Waris, Gulam

    2016-02-12

    Hepatitis C virus (HCV) relies on host lipids and lipid droplets for replication and morphogenesis. The accumulation of lipid droplets in infected hepatocytes manifests as hepatosteatosis, a common pathology observed in chronic hepatitis C patients. One way by which HCV promotes the accumulation of intracellular lipids is through enhancing de novo lipogenesis by activating the sterol regulatory element-binding proteins (SREBPs). In general, activation of SREBPs occurs during cholesterol depletion. Interestingly, during HCV infection, the activation of SREBPs occurs under normal cholesterol levels, but the underlying mechanisms are still elusive. Our previous study has demonstrated the activation of the inflammasome complex in HCV-infected human hepatoma cells. In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid droplet formation. NLRP3 inflammasome activation in HCV-infected cells enables caspase-1-mediated degradation of insulin-induced gene proteins. This subsequently leads to the transport of the SREBP cleavage-activating protein·SREBP complex from the endoplasmic reticulum to the Golgi, followed by proteolytic activation of SREBPs by S1P and S2P in the Golgi. Typically, inflammasome activation leads to viral clearance. Paradoxically, here we demonstrate how HCV exploits the NLRP3 inflammasome to activate SREBPs and host lipid metabolism, leading to liver disease pathogenesis associated with

  5. Stomach regulates energy balance via acylated ghrelin and desacyl ghrelin

    OpenAIRE

    Asakawa, A; Inui, A; Fujimiya, M; Sakamaki, R; Shinfuku, N; Ueta, Y; Meguid, M M; Kasuga, M

    2005-01-01

    Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance.

  6. Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

    Directory of Open Access Journals (Sweden)

    Arya J Bahrami

    Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

  7. Energy policy study. Volume 10. Nuclear power regulation

    International Nuclear Information System (INIS)

    Nikodem, Z.D.; Reynolds, A.W.; Clark, R.G.

    1980-05-01

    This report examines the programs for regulating the safety, design, and operation of domestic nuclear power plants. The first part of the study describes the Federal and State regulatory procedures. It describes the legal foundations for the Federal licensing process and the associated State regulatory activities. It then analyzes the aspects of these procedures that affect the cost and supply of nuclear-generated electricity. The second part of this study examines the effects of nuclear safety regulations on the planning and construction lead time for nuclear power stations, the cost of nuclear power, and, ultimately, the decision to invest in nuclear power

  8. Electrical energy industry regulation: trend in the international context

    International Nuclear Information System (INIS)

    Perez Arriaga, J.I.

    1995-01-01

    The regulation of the electric power industry is presently experiencing significative changes world-wide at an unprecedented pace. In these circumstances it is useless to attempt the preparation of a static snapshot of the current situation, because of the difficulties in capturing the exact position of each player and also because the picture would become obsolete in a very short time. This paper presents the specific features characterising power organisation, the regulatory approaches to the several services involved in supplying electricity, and alternative schemes for introduction of different levels of competition in traditionally regulated electric systems. (Author) 24 refs

  9. Innovation in energy networks. A study on the changing relation between regulation, technology and market in liberalized energy markets

    International Nuclear Information System (INIS)

    Kuenneke, R.W.; Bouwmans, I.; Kling, W.L.; Slootweg, J.G.; Stout, H.D.; De Vries, L.J.; Van Poelje, H.; Wolters, M.

    2001-10-01

    The purpose of this study is to contribute to the development a view on the future of the energy infrastructure for the next 10-15 years, including the related regulation, focusing on the strategic options for development of networks. Attention is paid to (1) planning concepts (to what extent should existing planning concepts be revised as a result of liberalization and technical innovation); and (2) positioning of networks (what are the consequences of the separation of energy markets in commercial and regulated sectors for the development of the energy sector) [nl

  10. The effect of building regulations on energy consumption in single family houses in Denmark

    DEFF Research Database (Denmark)

    Kjærbye, Vibeke; Larsen, Anders; Togeby, Mikael

    This paper explores how changes in regulatory requirements for energy efficiency in buildings (in the US also known as building energy codes) affect household energy consumption. The focus in this paper is on natural gas consumption by Danish single-family owner-occupied houses. Unlike most other...... advanced econometric methods we examine differences in heating energy consumption due to different building regulation requirements at the time of house construction. As for the effect of the building regulation, we find that changes in Danish building regulations have led to significant reductions...... in energy used for heating. The latest revision of the Danish building regulation covered by this paper is that of 1998. This revision has resulted in a 7% reduction in natural gas consumption....

  11. miR-217 Regulates Ethanol-Induced Hepatic Inflammation by Disrupting Sirtuin 1–Lipin-1 Signaling

    OpenAIRE

    Yin, Huquan; Liang, Xiaomei; Jogasuria, Alvin; Davidson, Nicholas O.; You, Min

    2015-01-01

    Ethanol-mediated injury, combined with gut-derived lipopolysaccharide (LPS), provokes generation of proinflammatory cytokines in Kupffer cells, causing hepatic inflammation. Among the mediators of these effects, miR-217 aggravates ethanol-induced steatosis in hepatocytes. However, the role of miR-217 in ethanol-induced liver inflammation process is unknown. Here, we examined the role of miR-217 in the responses to ethanol, LPS, or a combination of ethanol and LPS in RAW 264.7 macrophages and ...

  12. Economical regulation power through load shifting with smart energy appliances

    NARCIS (Netherlands)

    Vlot, M.C.; Knigge, J.D.; Slootweg, J.G.

    2013-01-01

    This paper considers the technical and economical feasibility of the introduction of automated demand response from domestic smart appliances in a European setting as a means to create a significant amount of regulating power. Simplified power-time flexibility models for appliances are introduced on

  13. Effects of Gut Microbes on Nutrient Absorption and Energy Regulation

    OpenAIRE

    Krajmalnik-Brown, Rosa; Ilhan, Zehra-Esra; Kang, Dae-Wook; DiBaise, John K.

    2012-01-01

    Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characteriz...

  14. International and European regulations in the energy law: selected issues

    International Nuclear Information System (INIS)

    Schwarz, F.

    2010-01-01

    This work deals with four selected legal aspects or issues in the energy sector, which are mainly located in the international, European and at the interface to national law. The first question is 'The status of the investor to the Energy Charter' and addresses issues regarding the investor position and their characteristics according to the Energy Charter Treaty. The second question is 'aspects of energy competence under the Treaty of Lisbon' and deals among others questions with the new energy expertise offense, as well as direct investment. The third issue, titled 'The admissibility of ownership unbundling' illuminates terms of a proposal, which plan a full ownership unbundling of transmission system operators, in more detail. The fourth issue is 'aspects for the implementation of directive 2006/32/EC' and deals with aspects of the implementation of this directive in Austria. This work is making an attempt to shed light on these questions and their issues in more detail by also taking into account the Austrian perspectives. In my view the energy sector is an economically important and politically embossed area that always has a current relevance to daily life and will raise more legal questions in future. (kancsar) [de

  15. Starvation and refeeding in rats: effect on some parameters of energy metabolism and electrolytes and changes of hepatic tissue

    Directory of Open Access Journals (Sweden)

    Fatemeh Namazi

    Full Text Available Abstract: Regarding the importance of starvation and refeeding and the occurrence of refeeding syndrome in various conditions, the present study was conducted to investigate the effects of refeeding on some parameters of energy metabolism and electrolytes and changes of hepatic tissue in male Wistar rats. Fifty-seven rats were divided into six groups, having 6 to 11 rats. Food was provided ad-libitum until three months and then the first group was considered without starvation (day 0. Other rats were fasted for two weeks. Group 2 was applied to a group immediately after starvation (day 14. Groups 3 to 6 were refed in days 16 till 22, respectively. At the end of each period, blood and tissue samples were taken and histopathological and serum analysis, including serum electrolytes (calcium, phosphorus, sodium, potassium, the energy parameters (glucose, insulin, cortisol and the liver enzymes (ALT, AST, ALP were determined. Insulin decreased by starvation and then showed an increasing trend compared to starvation period, which the highest amount of this parameter was observed eight days post-refeeding. Serum glucose level showed the opposite pattern of insulin. Histopathological examination of the tissue sections revealed clear vacuoles after starvation and refeeding, in which the severity of lesions gradually decreased during refeeding. The cortisol level decreased by starvation and then increased during refeeding. Also, potassium and phosphorus concentrations declined by refeeding and the serum sodium and potassium levels were changed in the relatively opposite manner. The calcium level decreased by starvation and then increased during refeeding. These results could help recognize and remedy the refeeding syndrome.

  16. Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

    Science.gov (United States)

    Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

    2012-01-01

    Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

  17. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate Package, Infringement

  18. Commission for Energy regulation (CRE) - Activity report june 2008; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2008 activity report of CRE. Content: A - How CRE works: CRE regulatory authority and organisation: Powers, Organisation; Budget resources; Personnel; B - The Standing Committee for Dispute Settlement and Sanctions (CoRDiS) activity: Admissibility, Authority; C - Building a single European energy market: Overview; Organisation and coordination of the main European regulators (Work carried out collectively by European regulators, Regulator organisation and development, CRE's relations with European Community institutions, Development of CEER activities outside the European Union); CRE's European activities (The contribution of European regulators to the Third Energy Package, Integration of gas markets, Integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, Opening up markets to benefit consumers); European Community activities (The European Commission's proposals for the internal energy market: the Third Energy Package, The European Commission's proposals for fighting climate change: the Climate

  19. Assessment of hepatic fatty infiltration using dual-energy computed tomography: a phantom study

    International Nuclear Information System (INIS)

    Li, Jung-Hui; Tsai, Chang-Yu; Huang, Hsuan-Ming

    2014-01-01

    The purpose of this study was to examine the performance of dual-energy computed tomography (DECT) for the quantification of liver fat content (LFC). We prepared two phantoms: homogenized mixtures of porcine liver and fat and homogeneous mixtures of liver- and fat-equivalent solutions. Tubes containing mixtures with known fat concentrations were scanned on a dual-source CT scanner using two DE scanning protocols (80 kV/Sn140 kV and 100 kV/Sn140 kV). Attenuation curves obtained from DECT were used to describe attenuations of various degrees of LFC at different energies. LFC was calculated from DECT data and compared with the known LFC. The phantom made of liver/fat mixtures was not used for liver fat quantification because the increase of fat content did not show a decline of CT numbers. This may be due to inhomogeneity as observed in CT images. Attenuation curves obtained from two DE scanning protocols had the ability to discriminate small differences in fat concentrations. Our results also showed a strong correlation between DECT measurements and known LFC (R 2  > 0.99, P < 0.005). DECT will be a reliable tool for liver fat quantification. Furthermore, attenuation curves obtained from DECT data can be used for discriminating various degrees of LFC. (paper)

  20. Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

    Science.gov (United States)

    Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

    2016-12-15

    Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. EU Directives, national regulations and incentives for photovoltaic solar energy

    International Nuclear Information System (INIS)

    Jager-Waldau, A.; Ossenbrink, H.; Scholz, H.; Bloem, H.; Werring, L.

    2004-01-01

    The European Union long-term strategy for security of energy supply and its commitment to curb climate change led to the adoption of a series of Strategy Papers and EU Directives. In all these, it is clearly stated that climate change is a long-term challenge for the international community and that the commitments made in the Kyoto Protocol can only be a first step. The promotion of renewable energies is a most important element of this process. It regards industry, jobs and foreign trade balance as well, generating benefit to social sustainability. Photovoltaic is a key technology with the potential not only to serve the needs in energy supply of tomorrow in a sustainable way, but already today, it can improve security and stability of electricity services at peak times, due to its decentralized nature. This paper gives an update on the EU and National legislation in place to promote the implementation of photovoltaic. (authors)

  2. Experience of regulatory body functioning in energy industry of Ukraine: Prospects for future development of state regulation of energy

    International Nuclear Information System (INIS)

    Oruskaya, M.

    2002-01-01

    Materials collected (presented) in the paper introduce to (familiarise) the audience with the main forms, methods and phases of the state regulation of energy industry in Ukraine in the period of transition to market economy. Special attention was paid to the following aspects: 1. Necessity and history of establishment of special regulatory body in Ukraine - The National Electricity Regulatory Commission (NERC); 2. The main tasks and authorities of NERC according to the Ukraine Law on Energy Sector; 3. Regulation mechanisms of the main processes in the energy industry used by the Commission on the current level of energy sector development and economic results of its introduction; 4. Problems with functioning of the wholesale energy market specifically as the main component of the Ukraine energy industry and trends of future development (improvement of energy industry's financial situation, intensification of competition between energy producers and suppliers, improvement of tariff and investment policies, etc.); 5. Necessity and ways of future improvement of the standards and legal basis for regulation in Ukraine. (author)

  3. Independent regulatory authorities - a comparative study of European energy regulators

    International Nuclear Information System (INIS)

    Sander Johansen, K.; Holm Pedersen, L.; Moll Soerensen, E.

    2004-04-01

    Independent regulatory authorities are widely recommended as part of the institutional design of liberalised energy markets - not least by the European Commission. This report describes and compares the regulatory authorities for energy in the EU. Arguments for regulatory independence are presented and discussed, and an index is developed to measure the degree of conformance to theories of regulatory independence. It is established that the main pattern of variation is that countries, which formerly had strong state-owned companies, have chosen to create regulatory authorities at state level with many institutional safeguards for independence. (au)

  4. Consumer engagement in alternative energy-Can the regulators and suppliers be trusted?

    International Nuclear Information System (INIS)

    Mumford, John; Gray, David

    2010-01-01

    The introduction of alternative energy requires collaboration between consumers, energy suppliers and regulators. A fundamental question is, will consumers engage with this agenda and, in particular, will they trust the institutions sufficiently to enable the collaborations that are needed. Present indications suggest that consumers have little trust in the established institutions and tend to reject such collaborations. This article presents two case studies which explore the way consumers, regulators and energy suppliers interact in relation to alternative energy projects. It analyses the inter-group interactions from the perspective of symbolic interactionism and discusses the aspects that undermine trust, leading to suggestions for improved trust.

  5. Signalling from the periphery to the brain that regulates energy homeostasis.

    Science.gov (United States)

    Kim, Ki-Suk; Seeley, Randy J; Sandoval, Darleen A

    2018-04-01

    The CNS regulates body weight; however, we still lack a clear understanding of what drives decisions about when, how much and what to eat. A vast array of peripheral signals provides information to the CNS regarding fluctuations in energy status. The CNS then integrates this information to influence acute feeding behaviour and long-term energy homeostasis. Previous paradigms have delegated the control of long-term energy homeostasis to the hypothalamus and short-term changes in feeding behaviour to the hindbrain. However, recent studies have identified target hindbrain neurocircuitry that integrates the orchestration of individual bouts of ingestion with the long-term regulation of energy balance.

  6. Consumer engagement in alternative energy. Can the regulators and suppliers be trusted?

    Energy Technology Data Exchange (ETDEWEB)

    Mumford, John [Senior Visiting Fellow, School of Management, University of Surrey (United Kingdom); Gray, David [Professor of Management Learning, School of Management, University of Surrey, GU2 7XH (United Kingdom)

    2010-06-15

    The introduction of alternative energy requires collaboration between consumers, energy suppliers and regulators. A fundamental question is, will consumers engage with this agenda and, in particular, will they trust the institutions sufficiently to enable the collaborations that are needed. Present indications suggest that consumers have little trust in the established institutions and tend to reject such collaborations. This article presents two case studies which explore the way consumers, regulators and energy suppliers interact in relation to alternative energy projects. It analyses the inter-group interactions from the perspective of symbolic interactionism and discusses the aspects that undermine trust, leading to suggestions for improved trust. (author)

  7. Consumer engagement in alternative energy-Can the regulators and suppliers be trusted?

    Energy Technology Data Exchange (ETDEWEB)

    Mumford, John, E-mail: John.Mumford@uk.bp.co [School of Management, University of Surrey (United Kingdom); Gray, David [School of Management, University of Surrey, GU2 7XH (United Kingdom)

    2010-06-15

    The introduction of alternative energy requires collaboration between consumers, energy suppliers and regulators. A fundamental question is, will consumers engage with this agenda and, in particular, will they trust the institutions sufficiently to enable the collaborations that are needed. Present indications suggest that consumers have little trust in the established institutions and tend to reject such collaborations. This article presents two case studies which explore the way consumers, regulators and energy suppliers interact in relation to alternative energy projects. It analyses the inter-group interactions from the perspective of symbolic interactionism and discusses the aspects that undermine trust, leading to suggestions for improved trust.

  8. Energy efficiency drivers in Europe. Regulations and other instruments open new horizons for energy management in buildings

    International Nuclear Information System (INIS)

    Obara, H.

    2010-01-01

    Curbing climate change and global warming will be one of the major challenges of the 21. Century.The very survival of our society could be at stake. Greenhouse gases including CO 2 have been identified as the culprits and the vast majority of industrialized countries have agreed to cut emissions drastically over coming decades. Buildings account for nearly 40% of the energy used in most countries and are responsible for a similar level of global CO 2 emissions. Energy efficiency in buildings is therefore one of the keys to reducing green-house emissions. The main driving force to achieve the ambitious goals that have been set for the reduction of greenhouse gases will come from energy efficiency regulations, building codes, standards, labels, certifications, obligations and incentives, all of which have been multiplying steadily over recent decades. International institutions are rolling out energy efficiency directives and standards that set minimum requirements for buildings.They are gradually being taken into account in national regulations and building codes. Today, most energy efficiency regulations concern building design. They hardly touch on Energy Management aspects that can generate major operational gains with relatively low investments and quick payback. Beyond regulations that focus on minimum requirements, environmental performance labels use building rating criteria that can take energy efficiency much further.They offer a practical way of assigning value to energy efficiency and in this way represent powerful market drivers. Moreover, the important benefits of Energy Management can be easily integrated in the rating criteria of these far-reaching schemes. Indeed, through effective building measurement, monitoring and control systems, Energy Management is one of the keys to rapidly reducing carbon emissions and achieving climate change targets. (author)

  9. Developmental programming of energy balance regulation: Is physical activity more "programmable" than food intake

    Science.gov (United States)

    Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mecha...

  10. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... friend, spouse, life partner, parent, sibling or other family member. What is HE? Hepatic Encephalopathy, sometimes referred ... disease is. It’s important for you and your family to become familiar with the signs of Hepatic ...

  11. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Hepatic Encephalopathy Back Hepatic ... Your Story Spread the Word Give While You Shop Contact Us Donate Now Help ALF Improve This ...

  12. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Now Hepatic Encephalopathy Back Hepatic Encephalopathy is a brain disorder that develops in some individuals with liver ... is a condition that causes temporary worsening of brain function in people with advanced liver disease. When ...

  13. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta.

    Science.gov (United States)

    Pazos, Patricia; Lima, Luis; Diéguez, Carlos; García, María C

    2014-01-01

    The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6), a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY) and agouti-related peptide (AgRP) and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART). Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18) were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice) on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  14. Energy Balance Regulating Neuropeptides Are Expressed through Pregnancy and Regulated by Interleukin-6 Deficiency in Mouse Placenta

    Directory of Open Access Journals (Sweden)

    Patricia Pazos

    2014-01-01

    Full Text Available The placenta produces a number of signaling molecules including metabolic and reproductive hormones as well as several inflammatory mediators. Among them, Interleukin-6 (IL-6, a well-known immune and metabolic regulator, acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. IL-6 interacts with key hypothalamic neuropeptidergic systems controlling energy homeostasis such as those producing the orexigenic/anabolic: neuropeptide Y (NPY and agouti-related peptide (AgRP and anorectic/catabolic neuropeptides: proopiomelanocortin (POMC and cocaine and amphetamine regulated transcript (CART. Human and rat placenta have been identified as source of these neuropeptides, but their expression and regulation in murine placental tissues remain unknown. Therefore, placental mRNA levels of IL-6, NPY, AgRP, POMC, and CART at different pregnancy stages (gestational days 13, 15, and 18 were analyzed by real time PCR, as were the effect of IL-6 deficiency (IL-6 knockout mice on their placental expression. Our results showed that placenta-derived neuropeptides were regulated by gestational age and IL-6 throughout the second half of mouse pregnancy. These data suggest that IL-6 may participate in the fine tune control of energy balance during pregnancy by extending its action as a metabolic signal to the main organ at the fetomaternal interface: the placenta.

  15. Act to amend cost regulations of the Atomic Energy Act

    International Nuclear Information System (INIS)

    1980-01-01

    Article 21 is replaced by articles 21 to 21b. According to this, fees or reimbursements for expenses for official acts (e.g. decisions, supervisory acts, safeguarding of nuclear fuels) as well as for the use of facilities according to article 9a, section 3, of the Atomic Energy Act (e.g. Laender facilities to collect nuclear waste). (HP) [de

  16. 75 FR 25121 - Revisions to Energy Efficiency Enforcement Regulations

    Science.gov (United States)

    2010-05-07

    ... the United States comply with DOE's energy conservation standards, the Department has promulgated... this RFI, DOE requests comments, information, and recommendations on the following concepts for the... third party fails to follow through on filing for the manufacturer or labeler? Should that recourse be...

  17. Determinants of Renewable Energy Innovation: Environmental Policies vs. Market Regulation

    International Nuclear Information System (INIS)

    Vona, Francesco; Nesta, Lionel; Nicolli, Francesco

    2012-02-01

    This paper carries out a comprehensive analysis of renewable energy innovations considering four mechanisms suggested by innovation models: 1. policy-inducement; 2. market structure; 3. demand and social cohesion- mainly proxied by income inequality; 4. characteristics of country knowledge base. For OECD countries and years 1970-2005, we build a unique dataset containing time-varying information on quality-adjusted patent production in renewable energy, the latter being a function of environmental policies, green R and D, entry barriers, knowledge stock, knowledge diversity and income inequality. We develop count data models using the Generalized Method of Moments (GMM) to account for endogeneity of policy support. Our synthetic policy index positively affects innovations especially in countries with deregulated energy markets and low entry barriers. The effect of entry barriers and inequality is negative and of similar magnitude as that of policy. Product market liberalization positively affects green patent generation, especially so when ambitious policies are adopted, when the initial level of public R and D expenditures and when the initial share of distributed energy generation is high. Our results are robust to alternative specifications, to the inclusion of technology-specific effects and to the use of quality-adjusted patents as dependent variables. In the latter case, the estimated effect of lowering entry barriers and of knowledge diversity almost double on citation count relatively to patent count. (authors)

  18. Alcohol and Hepatitis

    Science.gov (United States)

    ... Home » Living with Hepatitis » Daily Living: Alcohol Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... heavy drinking, most heavy drinkers have developed cirrhosis. Hepatitis C and cirrhosis In general, someone with hepatitis ...

  19. Hepatitis C: Treatment

    Science.gov (United States)

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  20. On the Use of Energy Storage Technologies for Regulation Services in Electric Power Systems with Significant Penetration of Wind Energy

    DEFF Research Database (Denmark)

    Yang, Bo; Makarov, Yuri; Desteese, John

    2008-01-01

    Energy produced by intermittent renewable resources is sharply increasing in the United States. At high penetration levels, volatility of wind power production could cause additional problems for the power system balancing functions such as regulation. This paper reports some partial results...... and frequently changing regulation signal. Several energy storage options have been analyzed based on thirteen selection criteria. The evaluation process resulted in the selection of flywheels, pumped hydro electric power (or conventional hydro electric power) plant and sodium sulfur or nickel cadmium batteries...... of a project work, recently conducted by the Pacific Northwest National Laboratory (PNNL) for Bonneville Power Administration (BPA). The project proposes to mitigate additional intermittency with the help of Wide Area Energy Management System (WAEMS) that would provide a two-way simultaneous regulation service...

  1. Development regulation changes local elected leaders can make to promote energy conservation

    Energy Technology Data Exchange (ETDEWEB)

    Kron, Jr, N F

    1980-07-01

    This report lists actions that local officials can make to change their community's development regulations and thereby lessen the effects of local energy problems. The term development regulations, as used here, is a general reference to local or state controls over land use and development that affect design, orientation, placement, location, and related characteristics of buildings and infrastructure. The regulations include items such as zoning, subdivision controls, setbacks, yard and height requirements, and solar-access ordinances.

  2. The role of leptin in the regulation of energy balance and adiposity

    NARCIS (Netherlands)

    van Dijk, G

    2001-01-01

    Since its discovery, leptin (a 167-amino acid product of the OB gene) has quickly moved to the forefront as an important hormone for regulation of energy balance. It closes a feedback loop from adipose tissue to hypothalamic neuropeptide-containing neural circuitry involved in regulation of food

  3. Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

    Science.gov (United States)

    Brain estrogen receptor-a (ERa) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERa expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic–pituitary–gonadal...

  4. Hepatitis C

    Science.gov (United States)

    ... an inflammation of the liver. One type, hepatitis C, is caused by the hepatitis C virus (HCV). It usually spreads through contact with ... childbirth. Most people who are infected with hepatitis C don't have any symptoms for years. If ...

  5. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  6. Hepatic Encephalopathy

    Science.gov (United States)

    ... Caregiver Support Caregiver Stories Home › What is Hepatic Encephalopathy? Why Your Liver is Important The Connection Between HE and Liver ... Why it’s Important to Treat HE Symptoms of Liver Failure Glossary of terms ... is Hepatic Encephalopathy? Hepatic Encephalopathy, sometimes referred to as portosystemic encephalopathy ...

  7. Hepatitis A

    Science.gov (United States)

    ... is an inflammation of the liver. One type, hepatitis A, is caused by the hepatitis A virus (HAV). The disease spreads through contact with ... suggest medicines to help relieve your symptoms. The hepatitis A vaccine can prevent HAV. Good hygiene can also ...

  8. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner.

    Directory of Open Access Journals (Sweden)

    Josef Köck

    Full Text Available Persistence of hepatitis B virus (HBV infection requires covalently closed circular (cccDNA formation and amplification, which can occur via intracellular recycling of the viral polymerase-linked relaxed circular (rc DNA genomes present in virions. Here we reveal a fundamental difference between HBV and the related duck hepatitis B virus (DHBV in the recycling mechanism. Direct comparison of HBV and DHBV cccDNA amplification in cross-species transfection experiments showed that, in the same human cell background, DHBV but not HBV rcDNA converts efficiently into cccDNA. By characterizing the distinct forms of HBV and DHBV rcDNA accumulating in the cells we find that nuclear import, complete versus partial release from the capsid and complete versus partial removal of the covalently bound polymerase contribute to limiting HBV cccDNA formation; particularly, we identify genome region-selectively opened nuclear capsids as a putative novel HBV uncoating intermediate. However, the presence in the nucleus of around 40% of completely uncoated rcDNA that lacks most if not all of the covalently bound protein strongly suggests a major block further downstream that operates in the HBV but not DHBV recycling pathway. In summary, our results uncover an unexpected contribution of the virus to cccDNA formation that might help to better understand the persistence of HBV infection. Moreover, efficient DHBV cccDNA formation in human hepatoma cells should greatly facilitate experimental identification, and possibly inhibition, of the human cell factors involved in the process.

  9. Eicosapentaenoic Acid-Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Liu, Yanjun; Shi, Di; Tian, Yingying; Liu, Yuntao; Zhan, Qiping; Xu, Jie; Wang, Jingfeng; Xue, Changhu

    2017-02-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca 2+ /calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.

  10. Commission of energy regulation. 2004 activity report; Commission de regulation de l'energie. Rapport d'activite 2004

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2004-07-01

    The commission of energy regulation (CRE) is an independent administrative authority in charge of the control of the operation of gas and electricity markets. This document is the fifth activity report of CRE and covers the July 1, 2003 - June 30, 2004 period, which corresponds to the era of opening of energy markets as a consequence of the enforcement of the June 26, 2003 European directive. In the framework of the stakes made by energy markets liberalization, this document presents the situation of the gas and electricity markets during this period (European framework, regulation of both markets, public utility mission..) and describes CRE's means for the monitoring of these markets. (J.S.)

  11. Differential regulation of metabolic parameters by energy deficit and hunger.

    Science.gov (United States)

    Kitka, Tamás; Tuza, Sebestyén; Varga, Balázs; Horváth, Csilla; Kovács, Péter

    2015-10-01

    Hypocaloric diet decreases both energy expenditure (EE) and respiratory exchange rate (RER), affecting the efficacy of dieting inversely. Energy deficit and hunger may be modulated separately both in human and animal studies by drug treatment or food restriction. Thus it is important to separate the effects of energy deficit and hunger on EE and RER. Three parallel and analogous experiments were performed using three pharmacologically distinct anorectic drugs: rimonabant, sibutramine and tramadol. Metabolic parameters of vehicle- and drug-treated and pair-fed diet-induced obese mice from the three experiments underwent common statistical analysis to identify effects independent of the mechanisms of action. Diet-induced obesity (DIO) test of tramadol was also performed to examine its anti-obesity efficacy. RER was decreased similarly by drug treatments and paired feeding throughout the experiment irrespective of the cause of reduced food intake. Contrarily, during the passive phase, EE was decreased more by paired feeding than by both vehicle and drug treatment irrespective of the drug used. In the active phase, EE was influenced by the pharmacological mechanisms of action. Tramadol decreased body weight in the DIO test. Our results suggest that RER is mainly affected by the actual state of energy balance; conversely, EE is rather influenced by hunger. Therefore, pharmacological medications that decrease hunger may enhance the efficacy of a hypocaloric diet by maintaining metabolic rate. Furthermore, our results yield the proposal that effects of anorectic drugs on EE and RER should be determined compared to vehicle and pair-fed groups, respectively, in animal models. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Epilepsy, Regulation of Brain Energy Metabolism and Neurotransmission

    OpenAIRE

    Cloix, Jean-Fran?ois; H?vor, Tobias

    2009-01-01

    Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine su...

  13. Study on Laws, Regulations and Standards on Energy Efficiency, Energy Conserving and Emission Reduction of Industrial Boilers in EU

    Science.gov (United States)

    Liu, Ren; Zhao, Yuejin; Chen, Haihong; Liang, Xiuying; Yang, Ming

    2017-12-01

    Industrial boilers are widely applied in such fields as factory power, building heating, and people’s lives; China is the world’s largest producer and user of industrial boilers, with very high annual energy consumption; clear requirements have been put forward by China on the energy efficiency since the “11th Five-year Plan” with the hope to save energy and reduce emission by means of energy efficiency standards and regulations on the supervision and control of various special equipment. So far, the energy efficiency of industrial boilers in China has been improved significantly but there is still a gap with the EU states. This paper analyzes the policies of energy efficiency, implementation models and methods of supervision and implementation at the EU level from laws, regulations, directives as well as standards; the paper also puts forward suggestions of energy conserving and emission reduction on the improvement of energy conserving capacity of industrial boilers in China through studying the legislations and measures of the developed countries in energy conserving of boilers.

  14. Guide to regulations on energy assessment of technical systems and energy labeling of buildings; Veileder til forskrift om energivurdering av tekniske anlegg og energimerking av bygninger

    Energy Technology Data Exchange (ETDEWEB)

    Bondy, Anne Cecilie Lyche; Isachsen, Olav Karstad

    2012-07-01

    The document represents the NVE's interpretation of the provisions of the Energy Labelling Regulations. In addition, the document contains information on energy labeling and energy assessment practical applications. (eb)

  15. Ion channels in the central regulation of energy and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Jong-Woo eSohn

    2013-05-01

    Full Text Available Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles for specific ion channels in the central pathways regulating food intake, energy expenditure, and glucose balance.

  16. Systemic risk in the energy sector—Is there need for financial regulation?

    International Nuclear Information System (INIS)

    Kerste, Marco; Gerritsen, Matthijs; Weda, Jarst; Tieben, Bert

    2015-01-01

    The credit crisis points at serious systemic risks in Over The Counter derivative trading. This has resulted in new financial regulation, covering both the financial sector and non-financial sectors. The actual extent to which non-financial companies trading on OTC markets contribute to systemic risk has hardly been the subject of research. This paper investigates the need for financial regulation in the energy sector, which shows a high use of OTC derivatives, by modeling systemic risk measured by the expected fraction of additional failing firms (EAF). Contagion risk within the energy sector and from the energy sector towards the banking sector is compared with that in other non-financial sectors. This paper adds to existing systemic risk literature by specifically looking at financial interdependence between a non-financial sector showing a high usage of OTC commodity derivatives and the banking sector, while contributing to the discussion on energy sector regulation with technical systemic risk analysis. Results indicate that contagion risk from the energy towards the banking sector is not relatively high compared to other non-financial sectors. Our results provide a first indication to question the need for generalized regulation of OTC derivative transactions, as recently introduced by the European Market Infrastructure Regulation (EMIR). - Highlights: • We assess the need for regulating OTC energy commodity derivatives under EMIR. • We present a methodology to model systemic risk in non-financial sectors. • We analyse direct and indirect channels for contagion giving rise to systemic risk. • Contagion risk from the energy towards the banking sector is not relatively high. • New EU regulation for energy OTC trading not supported by analysis of systemic risk

  17. Biomass as a Source of Renewable Energy in Spain: A Case Study in Regulating Renewable Energy

    OpenAIRE

    Sánchez Sáez, Antonio José

    2006-01-01

    This paper examines how, in Andalusia, the installation of plants producing biomass or processing electricity from renewable energies could conform to the public interest actions in Article 42 of the Andalusian Town Planning Act; and how the Andalusian Draft of Renewable Energies and Saving and Energy Efficiency proposes working out territorial plans for renewable energies for specific areas, where those zones enjoying the best conditions for the usage of these energies will be...

  18. Hypoksisk hepatitis

    DEFF Research Database (Denmark)

    Amadid, Hanan; Schiødt, Frank Vinholt

    2014-01-01

    Hypoxic hepatitis (HH), also known as ischaemic hepatitis or shock liver, is an acute liver injury caused by hepatic hypoxia. Cardiac failure, respiratory failure and septic shock are the main underlying conditions. In each of these conditions, several haemodynamic mechanisms lead to hepatic...... hypoxia. A shock state is observed in only 50% of cases. Thus, shock liver and ischaemic hepatitis are misnomers. HH can be a diagnostic pitfall but the diagnosis can be established when three criteria are met. Prognosis is poor and prompt identification and treatment of the underlying conditions...

  19. Controlling chaotic and hyperchaotic systems via energy regulation

    International Nuclear Information System (INIS)

    Laval, L.; M'Sirdi, N.K.

    2003-01-01

    This paper focuses on a new control approach to steer trajectories of chaotic or hyperchaotic systems towards stable periodic orbits or stationary points of interest. This approach mainly consists in a variable structure control (VSC) that we extend by explicitly considering the system energy as basis for both controller design and system stabilization. In this paper, we present some theoretical results for a class of nonlinear (possibly chaotic or hyperchaotic) systems. Then some capabilities of the proposed approach are illustrated through examples related to a four-dimensional hyperchaotic system

  20. Energy Management Systems and tertiary regulation in hierarchical control architectures for islanded micro-grids

    DEFF Research Database (Denmark)

    Sanseverino, Eleonora Riva; Di Silvestre, Maria Luisa; Quang, Ninh Nguyen

    2015-01-01

    In this paper, the structure of the highest level of a hierarchical control architecture for micro-grids is proposed. Such structure includes two sub-levels: the Energy Management System, EMS, and the tertiary regulation. The first devoted to energy resources allocation in each time slot based...

  1. Field Experience from Li-Ion BESS Delivering Primary Frequency Regulation in the Danish Energy Market

    DEFF Research Database (Denmark)

    Swierczynski, Maciej Jozef; Stroe, Daniel Ioan; Lærke, Rasmus

    2014-01-01

    In this paper it is presented the practical experience from operating a 1.6 MW/ 0.4 MWh lithium ion battery energy storage system, which is providing primary frequency regulation service on the Danish energy market. Aspects of the battery system requirements and the used control strategy...

  2. 75 FR 50950 - Federal Speculative Position Limits for Referenced Energy Contracts and Associated Regulations

    Science.gov (United States)

    2010-08-18

    ..., section 4a(a) of the Act authorized the Commission to establish position limits for contracts traded on or... Position Limits for Referenced Energy Contracts and Associated Regulations AGENCY: Commodity Futures... and option contracts based on a limited set of exempt commodities,\\1\\ namely certain energy...

  3. Radical innovation in the energy sector and the impact on regulation

    NARCIS (Netherlands)

    Lavrijssen, Saskia; Carrillo, Arturo

    2017-01-01

    The electricity sector is in a transition towards a Smart Energy System where the roles of private and institutional actors are evolving. This work deals with the influence of some technological innovations on the regulation of the energy sector. It identifies the main radical innovations in the

  4. Towards nearly zero-energy buildings: The state-of-art of national regulations in Europe

    International Nuclear Information System (INIS)

    Annunziata, Eleonora; Frey, Marco; Rizzi, Francesco

    2013-01-01

    Energy efficiency in buildings is an important objective of energy policy and strategy in Europe. A survey questionnaire was conducted among the 27 European Union Member States. This study aims to provide an overview of the current national regulatory framework focusing on three aspects: 1) integration of energy efficiency and renewable energy requirements, 2) translation of investments in energy saving into economic value, 3) commitment towards “nearly zero-energy” target. The study shows that European countries have adopted different approaches in the design of their national regulatory framework. This heterogeneity consists of four main factors: different authorities involved in energy regulations, traditional building regulations and enforcement models, different contextual characteristics, and maturity of the country in the implementation of energy efficiency measures. These differences are important to take into account country's profile in order to improve the sharing of best-practices and energy efficiency governance among European Union Member States. - Highlights: ► We analyze the legal status for energy efficient buildings in 27 European Countries. ► We examine building markets, renewable technology and “nearly zero-energy” targets. ► European Member States provide a heterogeneous environment to the recast of EPBD. ► National regulatory frameworks have evolved different structures and responsibilities. ► We provide directions in further enforcing energy efficiency in buildings regulation

  5. Epilepsy, regulation of brain energy metabolism and neurotransmission.

    Science.gov (United States)

    Cloix, Jean-François; Hévor, Tobias

    2009-01-01

    Seizures are the result of a sudden and temporary synchronization of neuronal activity, the reason for which is not clearly understood. Astrocytes participate in the control of neurotransmitter storage and neurotransmission efficacy. They provide fuel to neurons, which need a high level of energy to sustain normal and pathological neuronal activities, such as during epilepsy. Various genetic or induced animal models have been developed and used to study epileptogenic mechanisms. Methionine sulfoximine induces both seizures and the accumulation of brain glycogen, which might be considered as a putative energy store to neurons in various animals. Animals subjected to methionine sulfoximine develop seizures similar to the most striking form of human epilepsy, with a long pre-convulsive period of several hours, a long convulsive period during up to 48 hours and a post convulsive period during which they recover normal behavior. The accumulation of brain glycogen has been demonstrated in both the cortex and cerebellum as early as the pre-convulsive period, indicating that this accumulation is not a consequence of seizures. The accumulation results from an activation of gluconeogenesis specifically localized to astrocytes, both in vivo and in vitro. Both seizures and brain glycogen accumulation vary when using different inbred strains of mice. C57BL/6J is the most "resistant" strain to methionine sulfoximine, while CBA/J is the most "sensitive" one. The present review describes the data obtained on methionine sulfoximine dependent seizures and brain glycogen in the light of neurotransmission, highlighting the relevance of brain glycogen content in epilepsies.

  6. Code of laws and regulations on atomic energy controls. Showa 53 ed.

    International Nuclear Information System (INIS)

    1978-01-01

    The code has collected above laws and regulations promulgated by 10th February, 1978 and they can be classified into following several categories. 1. Atomic Energy Basic Law and Atomic Energy Commission Establishment Law including their related government orders, regulations and rules. 2. The Law for Regulation of Nuclear Source Material, Nuclear Fuel Material and regulations, rules, instructions and guidelines. 3. The Law on Technical Criteria for the Prevention of Radiation Hazards and the Law Concerning the Prevention of Radiation Hazards due to Radioisotopes, etc. including their related government orders, regulations, rules and announcements. 4. The Law on Compensation for Nuclear Damage with its relating government order and the Law on Indemnity Agreement for Compensation of Nuclear Damage. 5. Laws for establishing those nuclear energy development organizations as Japan Atomic Energy Research Institute, Japan Nuclear Ship Development Agency and Power Reactor and Nuclear Fuel Development Corporation. 6. Other laws relating to atomic energy and radiation utilization including their pertaining regulations, rules, standards, etc. such as: Electricity Business Law; Land Transportation and Cars Law; Ships and Vessels Safety Law; Aviation Law; Employees' Health and Safety Law; Electricity Resources Development Law; and others

  7. Hawaii Integrated Energy Assessment. Volume V. Rules, regulations, permits and policies affecting the development of alternate energy sources in Hawaii

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    A comprehensive presentaton of the major permits, regulations, rules, and controls which are likely to affect the development of alternate energy sources in Hawaii is presented. An overview of the permit process, showing the major categories and types of permits and controls for energy alternatives is presented. This is followed by a brief resume of current and projected changes designed to streamline the permit process. The permits, laws, regulations, and controls that are applicable to the development of energy alternatives in Hawaii are described. The alternate energy technologies affected, a description of the permit or control, and the requirements for conformance are presented for each applicable permit. Federal, state, and county permits and controls are covered. The individual energy technologies being considered as alternatives to the State's present dependence on imported fossil fuels are emphasized. The alternate energy sources covered are bioconversion, geothermal, ocean thermal, wind, solar (direct), and solid waste. For each energy alternative, the significant permits are summarized with a brief explanation of why they may be necessary. The framework of policy development at each of the levels of government with respect to the alternate energy sources is covered.

  8. Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-β1/Smad, nuclear factor-κB, and AKT signaling pathways in rats

    Directory of Open Access Journals (Sweden)

    Cao S

    2018-05-01

    -NF-κB-p65/NF-κB-p65, IL-1β, IL-6, and p-AKT/AKT significantly decreased after the treatment. Conclusion: These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-β1/Smad, NF-κB, and AKT signaling pathways and the reduction of extracellular matrix deposition. Keywords: hepatic fibrosis, Semen Brassicae, NF-κB, AKT, TGF-β1

  9. The future 2015 Danish Building Regulations concerning energy performance of multi framed windows

    DEFF Research Database (Denmark)

    Hacksen Kampmann, Thomas

    The future Danish Building Regulation BR 2015 will reduce energy consumption within the overall building stock. Regarding the very important field windows, it seems that BR 2015 will be based on the same rules as today, except for a simple reduction of the limits for energy loss. Since a big part...... of the total amount of energy consumption in buildings is lost through windows, and the regulations concerning multi framed windows are already highly problematic today, there is a risk of the problem getting bigger in the future....

  10. Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-β1/Smad, nuclear factor-κB, and AKT signaling pathways in rats.

    Science.gov (United States)

    Cao, Si; Zheng, Baoping; Chen, Tao; Chang, Xinfeng; Yin, Bao; Huang, Zhihua; Shuai, Ping; Han, Limin

    2018-01-01

    There is no effective treatment for liver fibrosis, which is a common phase during the progression of many chronic liver diseases to cirrhosis. Previous studies found that Semen Brassicae therapy can effectively improve the clinical symptoms of patients with asthma, allergic rhinitis, and chronic lung diseases; however, its effects on liver fibrosis in rats and its possible mechanisms of action remain unclear. Rats were injected intraperitoneally with 4% thioacetamide aqueous solution (5 mL·kg -1 ) at a dose of 200 mg·kg -1 twice a week for 8 consecutive weeks to establish the liver fibrosis model and were then treated with different concentrations of Semen Brassicae extract. After Semen Brassicae treatment, the morphology of the liver tissue was analyzed using hematoxylin and eosin and Masson's trichrome staining, and liver index and liver fibrosis grade were calculated. Thereafter, the levels of collagen-I, collagen-III, α-SMA, transforming growth factor (TGF)-β1, p-Smad 2/3, Smad 2/3, Smad4, NF-κB-p65, p-NF-κB-p65, IL-1β, IL-6, AKT, and p-AKT were determined using Western blotting. Compared with the untreated model group, the Semen Brassicae-treated group showed significantly decreased liver function indices; expression levels of collagen-I, collagen-III, and α-SMA; and hepatic fibrosis. Further studies also showed that the expression of TGF-β1, Smad4, p-Smad 2/3/Smad 2/3, p-NF-κB-p65/NF-κB-p65, IL-1β, IL-6, and p-AKT/AKT significantly decreased after the treatment. These results indicate that Semen Brassicae exhibits an anti-hepatic fibrosis effect, and the underlying mechanism of action may be related to the regulation of TGF-β1/Smad, NF-κB, and AKT signaling pathways and the reduction of extracellular matrix deposition.

  11. Activation of neuronal nitric oxide synthase in cerebellum of chronic hepatic encephalopathy rats is associated with up-regulation of NADPH-producing pathway.

    Science.gov (United States)

    Singh, Santosh; Trigun, Surendra K

    2010-09-01

    Cerebellum-associated functions get affected during mild hepatic encephalopathy (MHE) in patients with chronic liver failure (CLF). Involvement of nitrosative and antioxidant factors in the pathogenesis of chronic hepatic encephalopathy is an evolving concept and needs to be defined in a true CLF animal model. This article describes profiles of NADPH-dependent neuronal nitric oxide synthase (nNOS) and those of glutathione peroxidase and glutathione reductase (GR) vis-a-vis regulation of NADPH-producing pathway in the cerebellum of CLF rats induced by administration of thioacetamide (100 mg kg⁻¹ b.w., i.p.) up to 10 days and confirming MHE on Morris water maze tests. Significant increases in the expression of nNOS protein and nitric oxide (NOx) level coincided with a similar increment in NADPH-diaphorase activity in the cerebellum of CLF rats. Glutathione peroxidase and GR utilize NADPH to regenerate reduced glutathione (GSH) in the cells. Both these enzymes and GSH level were found to be static and thus suggested efficient turnover of GSH in the cerebellum of MHE rats. Relative levels of glucose-6-phosphate dehydrogenase (G6PD) vs. phosphofructokinase 2 (PFK2) determine the rate of pentose phosphate pathway (PPP) responsible to synthesize NADPH. The cerebellum of CLF rats showed overactivation of G6PD with a significant decline in the expression of PFK2 and thus suggested activation of PPP in the cerebellum during MHE. It is concluded that concordant activations of PPP and nNOS in cerebellum of MHE rats could be associated with the implication of NOx in the pathogenesis of MHE.

  12. Hepatitis C virus core protein expression leads to biphasic regulation of the p21 cdk inhibitor and modulation of hepatocyte cell cycle

    International Nuclear Information System (INIS)

    Nguyen, Hau; Mudryj, Maria; Guadalupe, Moraima; Dandekar, Satya

    2003-01-01

    Hepatitis C virus (HCV) Core protein is implicated in viral pathogenesis by the modulation of hepatocyte gene expression and function. To determine the effect of Core protein on the cell-cycle control of hepatocytes, a HepG2 cell line containing a Flag-tagged Core under the control of an inducible promoter was generated. Initial Core protein expression included the presence of unprocessed (191 aa) and processed (173 aa) forms of the Core proteins with the processed form becoming dominant later. Expression of the 191 aa form of Core protein corresponded to an increase in the expression of the p21, a decrease in cdk2-dependent kinase activity, and a decrease in the percentage of cells in S-phase along with an accumulation of cells in the G 0 /G 1 phase of the cell cycle. As the processed form accumulated, the p21 levels started to decline, suggesting that Core protein regulates p21 expression in a biphasic manner. These findings implicate Core protein in potentially modulating hepatocyte cell cycle differentially in the early stages of infection through biphasic regulation of p21 cdk kinase inhibitor

  13. Human Leukocyte Antigen (HLA and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

    Directory of Open Access Journals (Sweden)

    Nicole B. Crux

    2017-07-01

    Full Text Available The genetic factors associated with susceptibility or resistance to viral infections are likely to involve a sophisticated array of immune response. These genetic elements may modulate other biological factors that account for significant influence on the gene expression and/or protein function in the host. Among them, the role of the major histocompatibility complex in viral pathogenesis in particular human immunodeficiency virus (HIV and hepatitis C virus (HCV, is very well documented. We, recently, added a novel insight into the field by identifying the molecular mechanism associated with the protective role of human leukocyte antigen (HLA-B27/B57 CD8+ T cells in the context of HIV-1 infection and why these alleles act as a double-edged sword protecting against viral infections but predisposing the host to autoimmune diseases. The focus of this review will be reexamining the role of classical and non-classical HLA alleles, including class Ia (HLA-A, -B, -C, class Ib (HLA-E, -F, -G, -H, and class II (HLA-DR, -DQ, -DM, and -DP in immune regulation and viral pathogenesis (e.g., HIV and HCV. To our knowledge, this is the very first review of its kind to comprehensively analyze the role of these molecules in immune regulation associated with chronic viral infections.

  14. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Directory of Open Access Journals (Sweden)

    Angeliki Lyssimachou

    Full Text Available Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT, which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR and peroxisome proliferator-activated receptor gamma (PPARγ. In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  15. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  16. The Mammalian "Obesogen" Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish.

    Science.gov (United States)

    Lyssimachou, Angeliki; Santos, Joana G; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C Marisa R; Teixeira, Catarina; Castro, L Filipe C; Santos, Miguel M

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an "obesogenic" phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound.

  17. Competition in energy markets - law and regulation in the European Union

    International Nuclear Information System (INIS)

    Cameron, Peter Duncanson; Brothwood, Michael

    2002-03-01

    Analysis of the origins, aims and implementation of the EU energy directives is essential to an understanding of the emerging internal market in energy in the European Union. This book provides a detailed and practical account of the legislation and the various developments in the Member States that are leading to a competitive energy market for the first time. It explains the legislation, EU case law and the relevant national laws, regulations and competence of the enforcing authorities. (Author)

  18. Learning from the experiences of others: the development of energy regulation in UK and Greece

    International Nuclear Information System (INIS)

    Metcalf, R.; Rose, N.

    2002-01-01

    In this paper I have described how regulation of the energy sector has developed in two member states of the European Union. I have taken as my examples the UK and Greece. As the first country in the EU to advance to full market liberalisation the UK has already been through many phases of development in the energy sector and the process of regulation has had to adapt to deal with changing circumstances. Greece finds itself at a much earlier stage of development and regulation is a much newer factor in its energy market. It is hoped that by choosing two countries at different stages of developing their energy markets valuable examples can be found for challenges which are now being met in Croatia.(author)

  19. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  20. Designing and Testing Composite Energy Storage Systems for Regulating the Outputs of Linear Wave Energy Converters

    Directory of Open Access Journals (Sweden)

    Zanxiang Nie

    2017-01-01

    Full Text Available Linear wave energy converters generate intrinsically intermittent power with variable frequency and amplitude. A composite energy storage system consisting of batteries and super capacitors has been developed and controlled by buck-boost converters. The purpose of the composite energy storage system is to handle the fluctuations and intermittent characteristics of the renewable source, and hence provide a steady output power. Linear wave energy converters working in conjunction with a system composed of various energy storage devices, is considered as a microsystem, which can function in a stand-alone or a grid connected mode. Simulation results have shown that by applying a boost H-bridge and a composite energy storage system more power could be extracted from linear wave energy converters. Simulation results have shown that the super capacitors charge and discharge often to handle the frequent power fluctuations, and the batteries charge and discharge slowly for handling the intermittent power of wave energy converters. Hardware systems have been constructed to control the linear wave energy converter and the composite energy storage system. The performance of the composite energy storage system has been verified in experiments by using electronics-based wave energy emulators.

  1. Mitochondrial gene polymorphisms alter hepatic cellular energy metabolism and aggravate diet-induced non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Torsten Schröder

    2016-04-01

    Full Text Available Objective: Non-alcoholic fatty liver disease (NAFLD is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH. However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH. Methods: To determine the effect of a well-defined mitochondrial dysfunction on liver physiology at baseline and during dietary challenge, C57BL/6J-mtFVB/N mice were employed. This conplastic inbred strain has been previously reported to exhibit decreased mitochondrial respiration likely linked to a non-synonymous gene variation (nt7778 G/T of the mitochondrial ATP synthase protein 8 (mt-ATP8. Results: At baseline conditions, C57BL/6J-mtFVB/N mice displayed hepatic mitochondrial dysfunction characterized by decreased ATP production and increased formation of reactive oxygen species (ROS. Moreover, genes affecting lipid metabolism were differentially expressed, hepatic triglyceride and cholesterol levels were changed in these animals, and various acyl-carnitines were altered, pointing towards an impaired mitochondrial carnitine shuttle. However, over a period of twelve months, no spontaneous hepatic steatosis or inflammation was observed. On the other hand, upon dietary challenge with either a methionine and choline deficient diet or a western-style diet, C57BL/6J-mtFVB/N mice developed aggravated steatohepatitis as characterized by lipid accumulation, ballooning of hepatocytes and infiltration of immune cells. Conclusions: We observed distinct metabolic alterations in mice with a mitochondrial polymorphism associated hepatic mitochondrial

  2. Development perspectives of alternative energy projects before the new energy regulation

    International Nuclear Information System (INIS)

    Valencia V; Jaime A; Perez O, Jaime A; Moreno O, German

    2000-01-01

    Large electric energy generation systems are dominant in the energy markets. This has been like that, because the economic balances have not included yet some parameters, and specifically environmental variables, that started being considered in the international markets. Colombian generation and transmission expanding plans are commented and the possibilities for the developing of alternative energy projects are referred to those plans. Additionally, a regional experience in the definition of criteria for electric energy service coverage enlargement allowing for alternative energy inclusion is presents, remarking their successful application as a competitive alternative for rural energizing

  3. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

    Full Text Available Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver.

  4. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  5. Commission de regulation de l'energie. activity report 2015 - Reference document, 15 years of regulation

    International Nuclear Information System (INIS)

    2016-06-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the June 2015 activity report of CRE. The report comes in two volumes. The first provides comprehensive details of the CRE's activities in 2015, while the second highlights just how far the CRE has come since it was established in 2000. Content: A - Message from the Board; B - The Energy Regulatory Commission: The organisation and missions of CRE (organisation of CRE, missions of CRE, CRE and other institutional actors, CRE consultation and transparency, Human resources and budgetary means; CRE playing a role at the heart of Europe (CRE within ACER and CEER, Cooperation with other regulators; C - CRE and the markets: As part of its monitoring task, CRE assesses the wholesale market (The wholesale energy market has been affected by the significant fall in prices, The European regulation (REMIT) is a legal tool for monitoring the markets at European level, The capacity mechanism has been defined to promote the security of supply at national level); The retail market was growing fast in 2015 (The implementation of the NOME law provides a new legal framework for regulated tariffs

  6. Low hanging fruit? Regulations and energy efficiency in subsidized multifamily housing

    International Nuclear Information System (INIS)

    Reina, Vincent J.; Kontokosta, Constantine

    2017-01-01

    The U.S. government has invested in multifamily housing through an array of subsidized housing programs. These programs provide a venue for understanding how regulations governing multifamily housing can affect an owner's incentive to make energy efficient investments, and a tenant's desire to reduce their energy consumption levels. This paper empirically tests the impact of subsidized housing regulations on the energy efficiency of multi-family housing for low-income households. We begin by constructing a unique database that integrates actual energy use with physical, socioeconomic, and regulatory characteristics of all large multifamily properties in New York City, focusing on whether a property receives a federal rental subsidy. We employ multivariate regression models to examine the factors that influence energy consumption in multi-family buildings and compare subsidized housing to market-rate housing, controlling for a range of building and household characteristics. We find that subsidized properties are associated with higher energy consumption than similar market-rate properties and, of the subsidized housing programs, Public Housing tends to consume the most energy. Our results suggest that despite the potential for retrofitting multifamily properties, and associated cost, energy, and carbon emissions savings, regulatory factors constrain investment and consumption decisions in the case of subsidized properties. Reducing energy use in subsidized housing, therefore, rests on modifying existing regulations. - Highlights: • Developed a framework for why regulations affect utility consumption incentives. • Created and employed a dataset of actual energy use for all large properties in NYC. • Found that subsidized properties are associated with higher utility consumption. • Find that Public Housing tends to consume the most energy of the subsidy programs. • Find that regulatory factors affect investment and consumption decisions.

  7. The regulated energy economy versus the free energy market - The West German experience

    International Nuclear Information System (INIS)

    Liesen, K.; Schwarz, H.O.

    1989-09-01

    The overall good performance of the West German energy industry in terms of energy policy objectives such as security of supplies, competitiveness, efficient use of energy and environmental protection, is attributable to an energy policy based on the principles of the market economy and steady application of these same principles. Today, though, a debate, at times controversial, on whether more market influence or more government intervention is required is underway in West Germany; in view of the successes of energy policy and the balance struck between free enterprise and the government in the past, this debate has met with little understanding in some quarters. It is generally agreed, though, that the quality of the challenges energy policy and the energy industry in West Germany will confront in the future will remain essentially unchanged. West German energy policy will have to deal with: reestablishing a consensus on coal and nuclear power policy; achieving a high standard of environmental protection in the European Communities, and strengthening the position of the energy industry as efforts are made to get moves underway to create a single European market for energy underway. No fundamental change in the course of energy policy in the Federal Republic of Germany is needed to solve current energy policy issues or to preserve the underlying goals of this policy. An energy policy which continues to give priority where possible to market mechanisms as a means of adjustment and provides energy suppliers and users with a stable and reliable framework in which to operate, offers the best promise for meeting the challenges of the future. (author). 2 figs

  8. MiR-29b inhibits collagen maturation in hepatic stellate cells through down-regulating the expression of HSP47 and lysyl oxidase

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yifei; Ghazwani, Mohammed; Li, Jiang [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Sun, Ming; Stolz, Donna B. [Department of Cell Biology and Physiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261 (United States); He, Fengtian [Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038 (China); Fan, Jie [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Xie, Wen [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Li, Song, E-mail: sol4@pitt.edu [Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261 (United States)

    2014-04-18

    Highlights: • Enhanced HSP47 and LOX expression is associated with decreased miR-29b level in liver fibrosis. • miR-29b down-regulates HSP47 and LOX expression. • The suppression of HSP47 and LOX by miR-29b is mediated by putative sites at their 3′-UTRs. • miR-29b inhibits extracellular LOX activity and collagen maturation. - Abstract: Altered expression of miR-29b is implicated in the pathogenesis and progression of liver fibrosis. We and others previously demonstrated that miR-29b down-regulates the expression of several extracellular-matrix (ECM) genes including Col 1A1, Col 3A1 and Elastin via directly targeting their 3′-UTRs. However, whether or not miR-29b plays a role in the post-translational regulation of ECM biosynthesis has not been reported. Heat shock protein 47 (HSP47) and lysyl oxidase (LOX) are known to be essential for ECM maturation. In this study we have demonstrated that expression of HSP47 and LOX was significantly up-regulated in culture-activated primary rat hepatic stellate cells (HSCs), TGF-β stimulated LX-2 cells and liver tissue of CCl{sub 4}-treated mice, which was accompanied by a decrease of miR-29b level. In addition, over-expression of miR-29b in LX-2 cells resulted in significant inhibition on HSP47 and LOX expression. Mechanistically, miR-29b inhibited the expression of a reporter gene that contains the respective full-length 3′-UTR from HSP47 and LOX gene, and this inhibitory effect was abolished by the deletion of a putative miR-29b targeting sequence from the 3′-UTRs. Transfection of LX-2 cells with miR-29b led to abnormal collagen structure as shown by electron-microscopy, presumably through down-regulation of the expression of molecules involved in ECM maturation including HSP47 and LOX. These results demonstrated that miR-29b is involved in regulating the post-translational processing of ECM and fibril formation.

  9. MiR-29b inhibits collagen maturation in hepatic stellate cells through down-regulating the expression of HSP47 and lysyl oxidase

    International Nuclear Information System (INIS)

    Zhang, Yifei; Ghazwani, Mohammed; Li, Jiang; Sun, Ming; Stolz, Donna B.; He, Fengtian; Fan, Jie; Xie, Wen; Li, Song

    2014-01-01

    Highlights: • Enhanced HSP47 and LOX expression is associated with decreased miR-29b level in liver fibrosis. • miR-29b down-regulates HSP47 and LOX expression. • The suppression of HSP47 and LOX by miR-29b is mediated by putative sites at their 3′-UTRs. • miR-29b inhibits extracellular LOX activity and collagen maturation. - Abstract: Altered expression of miR-29b is implicated in the pathogenesis and progression of liver fibrosis. We and others previously demonstrated that miR-29b down-regulates the expression of several extracellular-matrix (ECM) genes including Col 1A1, Col 3A1 and Elastin via directly targeting their 3′-UTRs. However, whether or not miR-29b plays a role in the post-translational regulation of ECM biosynthesis has not been reported. Heat shock protein 47 (HSP47) and lysyl oxidase (LOX) are known to be essential for ECM maturation. In this study we have demonstrated that expression of HSP47 and LOX was significantly up-regulated in culture-activated primary rat hepatic stellate cells (HSCs), TGF-β stimulated LX-2 cells and liver tissue of CCl 4 -treated mice, which was accompanied by a decrease of miR-29b level. In addition, over-expression of miR-29b in LX-2 cells resulted in significant inhibition on HSP47 and LOX expression. Mechanistically, miR-29b inhibited the expression of a reporter gene that contains the respective full-length 3′-UTR from HSP47 and LOX gene, and this inhibitory effect was abolished by the deletion of a putative miR-29b targeting sequence from the 3′-UTRs. Transfection of LX-2 cells with miR-29b led to abnormal collagen structure as shown by electron-microscopy, presumably through down-regulation of the expression of molecules involved in ECM maturation including HSP47 and LOX. These results demonstrated that miR-29b is involved in regulating the post-translational processing of ECM and fibril formation

  10. Commission for Energy regulation (CRE) - Activity report June 2005; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2005 activity report of CRE. Content: A - The opening of the markets in France and in Europe: The opening of the markets one year after 1 July 2004 (An especially important step, Electricity and gas: a common framework with structural differences, The coexistence of market prices and regulated tariffs); The European texts of 26 June 2003 (Texts to give new impetus, Texts to harmonize the role and powers of national regulators, Texts to guarantee the independence of system operators, Texts to ensure transparent and non-discriminatory access to networks, Texts providing for strengthening of interconnections); The outlook for 2007, a fully open market (1 July 2007: a date set by the directives, Priority given to informing and protecting consumers); B - Regulation of the natural gas market: The gas market in the European context (Europe's dependency on imports is increasing, Gas prices increased considerably across the whole of Europe in 2004, The European gas scene continues to be dominated by a small number of players, Gas infrastructures need to be developed in Europe, The new European

  11. Commission for Energy regulation (CRE) - Activity report June 2005; Commission de regulation de l'energie (CRE) - Rapport d'activite juin 2005

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2005 activity report of CRE. Content: A - The opening of the markets in France and in Europe: The opening of the markets one year after 1 July 2004 (An especially important step, Electricity and gas: a common framework with structural differences, The coexistence of market prices and regulated tariffs); The European texts of 26 June 2003 (Texts to give new impetus, Texts to harmonize the role and powers of national regulators, Texts to guarantee the independence of system operators, Texts to ensure transparent and non-discriminatory access to networks, Texts providing for strengthening of interconnections); The outlook for 2007, a fully open market (1 July 2007: a date set by the directives, Priority given to informing and protecting consumers); B - Regulation of the natural gas market: The gas market in the European context (Europe's dependency on imports is increasing, Gas prices increased considerably across the whole of Europe in 2004, The European gas scene continues to be dominated by a small number of players, Gas infrastructures need to be developed in Europe, The new

  12. Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

    Science.gov (United States)

    Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

    2013-01-01

    We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

    KAUST Repository

    Ritho, Joan

    2015-07-23

    SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.

  14. A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress

    KAUST Repository

    Ritho, Joan; Arold, Stefan T.; Yeh, Edward  T.H.

    2015-01-01

    SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell’s energy equilibrium.

  15. Commission de regulation de l'energie. Activity Report June 2003

    International Nuclear Information System (INIS)

    2003-06-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the June 2003 activity report of CRE. Content: A - Energy markets regulation: a new step; B - Gas market regulation: gas markets and actors, gas market regulation (legal and institutional framework, networks access, methane terminals and modulation services, freedom spaces, European market regulation, gas utility, CRE gas activities and priorities in 2003); C - Electricity market regulation: electricity markets (European markets, operators activity on the French market), French electricity market regulation (public networks access, trans-border power exchanges, EDF's un-bundled accounts audit, market operation), electric utility in the regulated market (public utility content, public utility charges, power generation public utility financing, electricity pre-tax sale tariffs for non-eligible customers); D - CRE operation (means and resources, exercise of its implementing powers, European and international activities); E - Appendixes: Glossary; Units and conversions; Council of European Energy Regulators, Index of figures and tables

  16. Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.

    Science.gov (United States)

    Garaigorta, Urtzi; Heim, Markus H; Boyd, Bryan; Wieland, Stefan; Chisari, Francis V

    2012-10-01

    Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.

  17. Farnesoid X Receptor as a homeostat for hepatic nutrient metabolism, proliferation and intestinal inflammation : Novel insights into mechanisms of regulation

    NARCIS (Netherlands)

    Massafra, V

    2017-01-01

    Our body hosts several molecules that function as hormones to regulate metabolism in the liver. Bile acids (BAs) are molecules produced by the liver and stored in the gall bladder. After eating a meal, BAs are secreted in the intestine, where they help the digestion of fats and vitamins.

  18. Globalization of the energy sector - a U.S. regulator`s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Kallaur, Carolita [Offshore Minerals Management, U.S. Department of the Interior (United States)

    1998-12-01

    This publication relates to globalization of the energy sector addressing issues of significant importance to the United States. The author touches upon a number of activities MMS (Mineral Management Service) is involved in with a focus on a joint project being engaged in with NPD (Norwegian Petroleum Directorate) to help the Russian Federation develop a safety and environment regime for its offshore. The aim of the project are national standards that set requirements for local and regional governments, safety and environment requirements that conform to international standards, apply to both Russian and foreign firms, and sharing of best practices between NPD, MMS and Russian authorities

  19. Analysis on effects of energy efficiency regulations & standards for industrial boilers in China

    Science.gov (United States)

    Liu, Ren; Chen, Lili; Zhao, Yuejin; Liu, Meng

    2017-11-01

    The industrial boilers in China are featured by large quantity, wide distribution, high energy consumption and heavy environmental pollution, which are key problems faced by energy conservation and environmental protection in China. Meanwhile, industrial boilers are important equipment for national economy and people’s daily life, and energy conservation gets through all segments from type selection, purchase, installation and acceptance to fuel management, operation, maintenance and service. China began to implement such national mandatory standards and regulations for industrial boiler as GB24500-2009 The Minimum Allowable Values of Energy Efficiency and Energy Efficiency Grades of Industrial Boilers and TSG G002-2010 Supervision Regulation on Energy-Saving Technology for Boilers since 2009, which obviously promote the development of energy conservation of industrial boilers, but there are also some problems with the rapid development of technologies for energy conservation of industrial boilers. In this paper, the implementation of energy efficiency standards for industrial boilers in China and the significance are analyzed based on survey data, and some suggestions are proposed for the energy efficiency standards for industrial boilers. Support by Project 2015424050 of Special Fund for quality control Research in the Public Interest

  20. Tensions between Scottish National Policies for onshore wind energy and local dissatisfaction - insights from regulation theory

    Energy Technology Data Exchange (ETDEWEB)

    Parkhill, Karen [School of Psychology, Tower Building, Cardiff University, Cardiff, (United Kingdom)

    2007-09-15

    Although best described as a meta theory addressing the endurance of capitalism, regulation theory can successfully be used to explore not only the economic dimensions, but also the political, socio-cultural and environmental dimensions of particular developmental strategies. Thus, it offers a framework for embedding abstract debates about social attitudes to new technologies within debates about real regulation - the economic, social and cultural relationships operating through particular places. This paper uses regulation theory and qualitative, interview-based data to analyse Scotland's drive for onshore wind energy. This approach teases out how responses to wind farms are bound up with wider debates about how rural spaces are, and should be, regulated; the tensions within and between national political objectives, local political objectives and local communities' dissatisfaction; and the connections between local actors and more formal dimensions of renewable energy policy. (Author)

  1. Feature Hepatitis: Hepatitis Can Strike Anyone

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Feature Hepatitis Hepatitis Can Strike Anyone Past Issues / Spring 2009 Table ... from all walks of life are affected by hepatitis, especially hepatitis C, the most common form of ...

  2. Autophagy in hypothalamic AgRP neurons regulates food intake and energy balance

    OpenAIRE

    Kaushik, Susmita; Rodriguez-Navarro, Jose Antonio; Arias, Esperanza; Kiffin, Roberta; Sahu, Srabani; Schwartz, Gary J.; Cuervo, Ana Maria; Singh, Rajat

    2011-01-01

    Macroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here, we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the...

  3. Corporate-NGO partnerships as a form of civil regulation: lessons from the energy biodiversity initiative

    OpenAIRE

    Stephen Tully

    2004-01-01

    This paper will assess the prospects of so-called 'civil' regulation, or the ability of non-governmental organisations (NGOs), to regulate commercial behaviour within the institutional setting of a partnership. The selected case study involves an initiative between five conservation NGOs and five energy firms seeking to integrate biodiversity considerations into upstream oil and gas development projects within, or adjacent to, environmentally-sensitive or protected areas. Part one describes t...

  4. Ion channels in the central regulation of energy and glucose homeostasis

    OpenAIRE

    Sohn, Jong-Woo

    2013-01-01

    Ion channels are critical regulators of neuronal excitability and synaptic function in the brain. Recent evidence suggests that ion channels expressed by neurons within the brain are responsible for regulating energy and glucose homeostasis. In addition, the central effects of neurotransmitters and hormones are at least in part achieved by modifications of ion channel activity. This review focuses on ion channels and their neuronal functions followed by a discussion of the identified roles fo...

  5. Hepatic Encephalopathy

    Medline Plus

    Full Text Available ... Plan Long-Term Considerations Patient Support Finding Support Services Peer Support Groups Financial Assistance Support for My ... is Hepatic Encephalopathy? Why Your Liver is ...

  6. Subsidies in WTO Law and Energy Regulation : Some Implications for Fossil Fuels and Renewable Energy

    NARCIS (Netherlands)

    Marhold, Anna

    2018-01-01

    This contribution discusses WTO subsidies disciplines in the context of the energy sector. After laying out the relevant disciplines, it will discuss the paradox of WTO law with respect to subsidies towards fossil fuels vis-à-vis those towards renewable energy. It is clear that subsidies on clean

  7. Peroxisome proliferator-activated receptor α agonist-induced down-regulation of hepatic glucocorticoid receptor expression in SD rats

    International Nuclear Information System (INIS)

    Chen Xiang; Li Ming; Sun Weiping; Bi Yan; Cai Mengyin; Liang Hua; Yu Qiuqiong; He Xiaoying; Weng Jianping

    2008-01-01

    It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11β-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPARα), which is quickly induced by glucocorticoid in the liver. However, it is not clear if GR expression is changed by fenofibrate-induced PPARα activation. In this study, we tested this possibility in the liver of Sprague-Dawley rats. GR expression was reduced by fenofibrate in a time- and does-dependent manner. The inhibition was observed in liver, but not in fat and muscle. The corticosterone level in the blood was increased significantly by fenofibrate. These effects of fenofibrate were abolished by PPARα inhibitor MK886, suggesting that fenofibrate activated through PPARα. In conclusion, inhibition of GR expression may represent a new molecular mechanism for the negative feedback regulation of GR activity by PPARα

  8. Liver X receptor regulates hepatic nuclear O-GlcNAc signaling and carbohydrate responsive element-binding protein activity

    DEFF Research Database (Denmark)

    Bindesbøll, Christian; Fan, Qiong; Nørgaard, Rikke C

    2015-01-01

    in response to feeding, which is believed to be mediated by insulin. We have previously shown that LXRs are targets for glucose-hexosamine-derived O-linked β-N-acetylglucosamine (O-GlcNAc) modification enhancing their ability to regulate SREBP-1c promoter activity in vitro. To elucidate insulin...... of glycolytic and lipogenic enzymes, including glucokinase (GK), SREBP-1c, ChREBPα, and the newly identified shorter isoform ChREBPβ. Furthermore, glucose-dependent increases in LXR/retinoid X receptor-regulated luciferase activity driven by the ChREBPα promoter was mediated, at least in part, by O-GlcNAc...... transferase (OGT) signaling in Huh7 cells. Moreover, we show that LXR and OGT interact and colocalize in the nucleus and that loss of LXRs profoundly reduced nuclear O-GlcNAc signaling and ChREBPα promoter binding activity in vivo. In summary, our study provides evidence that LXRs act as nutrient and glucose...

  9. Travelers' Health: Hepatitis C

    Science.gov (United States)

    ... Chapter 3 - Hepatitis B Chapter 3 - Hepatitis E Hepatitis C Deborah Holtzman INFECTIOUS AGENT Hepatitis C virus ( ... mother to child. Map 3-05. Prevalence of hepatitis C virus infection 1 PDF Version (printable) 1 ...

  10. Travelers' Health: Hepatitis A

    Science.gov (United States)

    ... 3 - Helminths, Soil-Transmitted Chapter 3 - Hepatitis B Hepatitis A Noele P. Nelson INFECTIOUS AGENT Hepatitis A ... hepatitis/HAV Table 3-02. Vaccines to prevent hepatitis A VACCINE TRADE NAME (MANUFACTURER) AGE (Y) DOSE ...

  11. Hepatitis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

  12. Travelers' Health: Hepatitis B

    Science.gov (United States)

    ... Chapter 3 - Hepatitis A Chapter 3 - Hepatitis C Hepatitis B Francisco Averhoff INFECTIOUS AGENT Hepatitis B virus ( ... progression of disease. Map 3-04. Prevalence of hepatitis B virus infection 1 PDF Version (printable) 1 ...

  13. Hepatitis C: Clinical Trials

    Science.gov (United States)

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  14. Hepatitis C: Mental Health

    Science.gov (United States)

    ... the Public Home Hepatitis A Hepatitis B Hepatitis C Hepatitis C Home Getting Tested Just Diagnosed Treatment Choice Program ... Pain Mental Health Sex and Sexuality (for Hepatitis C) Success Stories FAQs For Health Care Providers Provider ...

  15. Transcriptional regulation of human and rat hepatic lipid metabolism by the grapefruit flavonoid naringenin: role of PPARalpha, PPARgamma and LXRalpha.

    Directory of Open Access Journals (Sweden)

    Jonathan Goldwasser

    2010-08-01

    Full Text Available Disruption of lipid and carbohydrate homeostasis is an important factor in the development of prevalent metabolic diseases such as diabetes, obesity, and atherosclerosis. Therefore, small molecules that could reduce insulin dependence and regulate dyslipidemia could have a dramatic effect on public health. The grapefruit flavonoid naringenin has been shown to normalize lipids in diabetes and hypercholesterolemia, as well as inhibit the production of HCV. Here, we demonstrate that naringenin regulates the activity of nuclear receptors PPARalpha, PPARgamma, and LXRalpha. We show it activates the ligand-binding domain of both PPARalpha and PPARgamma, while inhibiting LXRalpha in GAL4-fusion reporters. Using TR-FRET, we show that naringenin is a partial agonist of LXRalpha, inhibiting its association with Trap220 co-activator in the presence of TO901317. In addition, naringenin induces the expression of PPARalpha co-activator, PGC1alpha. The flavonoid activates PPAR response element (PPRE while suppressing LXRalpha response element (LXRE in human hepatocytes, translating into the induction of PPAR-regulated fatty acid oxidation genes such as CYP4A11, ACOX, UCP1 and ApoAI, and inhibition of LXRalpha-regulated lipogenesis genes, such as FAS, ABCA1, ABCG1, and HMGR. This effect results in the induction of a fasted-like state in primary rat hepatocytes in which fatty acid oxidation increases, while cholesterol and bile acid production decreases. Our findings explain the myriad effects of naringenin and support its continued clinical development. Of note, this is the first description of a non-toxic, naturally occurring LXRalpha inhibitor.

  16. U.S. Laws and Regulations for Renewable Energy Grid Interconnections

    Energy Technology Data Exchange (ETDEWEB)

    Chernyakhovskiy, Ilya [National Renewable Energy Lab. (NREL), Golden, CO (United States); Tian, Tian [National Renewable Energy Lab. (NREL), Golden, CO (United States); McLaren, Joyce [National Renewable Energy Lab. (NREL), Golden, CO (United States); Miller, Mackay [National Renewable Energy Lab. (NREL), Golden, CO (United States); Geller, Nina [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2016-09-01

    Rapidly declining costs of wind and solar energy technologies, increasing concerns about the environmental and climate change impacts of fossil fuels, and sustained investment in renewable energy projects all point to a not-so-distant future in which renewable energy plays a pivotal role in the electric power system of the 21st century. In light of public pressures and market factors that hasten the transition towards a low-carbon system, power system planners and regulators are preparing to integrate higher levels of variable renewable generation into the grid. Updating the regulations that govern generator interconnections and operations is crucial to ensure system reliability while creating an enabling environment for renewable energy development. This report presents a chronological review of energy laws and regulations concerning grid interconnection procedures in the United States, highlighting the consequences of policies for renewable energy interconnections. Where appropriate, this report places interconnection policies and their impacts on renewable energy within the broader context of power market reform.

  17. The Flavonoid Quercetin Ameliorates Liver Inflammation and Fibrosis by Regulating Hepatic Macrophages Activation and Polarization in Mice

    Directory of Open Access Journals (Sweden)

    Xi Li

    2018-02-01

    Full Text Available At present, there are no effective antifibrotic drugs for patients with chronic liver disease; hence, the development of antifibrotic therapies is urgently needed. Here, we performed an experimental and translational study to investigate the potential and underlying mechanism of quercetin treatment in liver fibrosis, mainly focusing on the impact of quercetin on macrophages activation and polarization. BALB/c mice were induced liver fibrosis by carbon tetrachloride (CCl4 for 8 weeks and concomitantly treated with quercetin (50 mg/kg or vehicle by daily gavage. Liver inflammation, fibrosis, and hepatic stellate cells (HSCs activation were examined. Moreover, massive macrophages accumulation, M1 macrophages and their related markers, such as tumor necrosis factor (TNF-α, interleukin (IL-1β, IL-6, and monocyte chemotactic protein-1 (MCP-1 in livers were analyzed. In vitro, we used Raw 264.7 cells to examine the effect of quercetin on M1-polarized macrophages activation. Our results showed that quercetin dramatically ameliorated liver inflammation, fibrosis, and inhibited HSCs activation. These results were attributed to the reductive recruitment of macrophages (F4/80+ and CD68+ into the liver in quercetin-treated fibrotic mice confirmed by immunostaining and expression levels of marker molecules. Importantly, quercetin strongly inhibited M1 polarization and M1-related inflammatory cytokines in fibrotic livers when compared with vehicle-treated mice. In vitro, studies further revealed that quercetin efficiently inhibited macrophages activation and M1 polarization, as well as decreased the mRNA expression of M1 macrophage markers such as TNF-α, IL-1β, IL-6, and nitric oxide synthase 2. Mechanistically, the inhibition of M1 macrophages by quercetin was associated with the decreased levels of Notch1 expression on macrophages both in vivo and in vitro. Taken together, our data indicated that quercetin attenuated CCl4-induced liver inflammation and

  18. Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

    Directory of Open Access Journals (Sweden)

    Michaela Kaldenbach

    Full Text Available BACKGROUND: Hepatocyte transplantation (HT is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. METHODS: Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa. RESULTS: Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. CONCLUSION: This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and

  19. Wedelolactone Regulates Lipid Metabolism and Improves Hepatic Steatosis Partly by AMPK Activation and Up-Regulation of Expression of PPARα/LPL and LDLR.

    Directory of Open Access Journals (Sweden)

    Yun Zhao

    Full Text Available Hyperlipidemia is considered one of the greatest risk factors of cardiovascular diseases. We investigated the anti-hyperlipidemic effect and the underlying mechanism of wedelolactone, a plant-derived coumestan, in HepG2 cells and high-fat diet (HFD-induced hyperlipidemic hamsters. We showed that in cultured HepG2 cells, wedelolactone up-regulated protein levels of adenosine monophosphate activated protein kinase (AMPK and peroxisome proliferator-activated receptor-alpha (PPARα as well as the gene expression of AMPK, PPARα, lipoprotein lipase (LPL, and the low-density lipoprotein receptor (LDLR. Meanwhile, administration of wedelolactone for 4 weeks decreased the lipid profiles of plasma and liver in HFD-induced hyperlipidemic hamsters, including total cholesterol (TC, triglycerides (TG, and low-density lipoprotein-cholesterol (LDL-C. The activation of AMPK and up-regulation of PPARα was also observed with wedelolactone treatment. Furthermore, wedelolactone also increased the activities of superoxidase dismutase (SOD and glutathione peroxidase (GSH-Px and decreased the level of the lipid peroxidation product malondialdehyde (MDA in the liver, therefore decreasing the activity of alanine aminotransferase (ALT. In conclusion, we provide novel experimental evidence that wedelolactone possesses lipid-lowering and steatosis-improving effects, and the underlying mechanism is, at least in part, mediated by the activation of AMPK and the up-regulation of PPARα/LPL and LDLR.

  20. The impact of the new wave of financial regulation for European energy markets

    International Nuclear Information System (INIS)

    Nijman, Luuk

    2012-01-01

    As the financial and physical markets for energy have increasingly become intertwined, energy trade is also covered by financial legislation. The European Commission wishes to strengthen this financial regulation of energy trade. It has put forward a set of regulatory proposals aimed at stabilizing financial markets and limiting volatility of energy prices. The most noteworthy are EMIR, MAD, REMIT and the revised MiFID. Key elements are transparency, new trading venues, central clearing obligations and mandatory transaction reporting. This article evaluates the likely outcomes for energy markets, given the new incentives for market parties. It argues that although there is no ground to exempt particular energy market participants such as energy companies from financial legislation, increased regulation will not necessarily bring about the effects the Commission desires. The causal link between derivatives trading and volatility of energy prices is not known precisely and many of the economic effects of the proposed legislation are theoretically and empirically ambiguous. Moreover, potentially conflicting instruments and objectives risk policy inconsistency. - Highlights: ► The European Commission has put forward a set of financial legislation to stabilize both financial markets and energy prices. ► This article assesses the impact of this financial regulation on energy markets. ► It shows that the theoretical and empirical effects of key elements in this legislation are ambiguous. ► It argues that, if enacted, particular market parties such as energy companies should not be exempted. ► It concludes that this set of legislation will not necessarily bring about the effects the Commission desires.

  1. A study on how to divide and recodify the atomic energy act and its related regulations

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Hui; Chung, Sang Ki; Lee, Sang Soo [Hannam Univ., Taejon (Korea, Republic of); Myung, Jae Jin [Chungnam National Univ., Taejon (Korea, Republic of)

    2003-02-15

    As a part of big project named 'streamlining and optimization of nuclear safety regulatory system', this report focuses on how to divide and recodify the Atomic Energy Act and its related regulations. Follow the first chapter of preface, the second chapter shows the systemic problems of regulation of current AEA and out strategy to reform and re-systematize it. This report concludes that the regulations of the current AEA need to be divided in three parts, i.e. the presidential regulations of FWAAE, NNA and RPA and the ministerial regulation of AEA in two part, i.e. that of NNA and RPA. Then the problems of current regulations of AEA are pointed out and the alternative regulations of FWAAE and NNA are persented in the third and forth chapter respectively. In the fifth chapter RPA is persented. And finally the legal character of several nuclear safety standards is estimated. Concerning nuclear safety or technology standards, those issued by Minister of Science and Technology (MST) empowered by law or its regulation is obviously forceful as a law. But the standards made by KINS to meet the tasks entrusted to KINS by MST is only conditionally forceful as a law, that is, on the condition that law or regulation empowered the chief of KINS to make nuclear safety and/or technology standards.

  2. Application of the EC eco-audit regulation in the energy industry

    International Nuclear Information System (INIS)

    Schulz, J.

    1994-01-01

    The eco-audit regulation isolates the precision of goals to improve operational environmental protection for observation, particularly with a view to the industrial energy economy. It is not wise without an investigation into the possible repercussions with other EU and national regulatory laws. Keywords here are: design of a heat application regulation according to the BImSchG, discussion over the introduction of an EC CO 2 Energy tax as well as the EC guidelines on reducing CO 2 emissions (SAVE). (orig./HP) [de

  3. Rictor/mTORC2 facilitates central regulation of energy and glucose homeostasis

    OpenAIRE

    Kocalis, Heidi E.; Hagan, Scott L.; George, Leena; Turney, Maxine K.; Siuta, Michael A.; Laryea, Gloria N.; Morris, Lindsey C.; Muglia, Louis J.; Printz, Richard L.; Stanwood, Gregg D.; Niswender, Kevin D.

    2014-01-01

    Insulin signaling in the central nervous system (CNS) regulates energy balance and peripheral glucose homeostasis. Rictor is a key regulatory/structural subunit of the mTORC2 complex and is required for hydrophobic motif site phosphorylation of Akt at serine 473. To examine the contribution of neuronal Rictor/mTORC2 signaling to CNS regulation of energy and glucose homeostasis, we utilized Cre-LoxP technology to generate mice lacking Rictor in all neurons, or in either POMC or AgRP expressing...

  4. The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats.

    Directory of Open Access Journals (Sweden)

    Yinghua Shi

    Full Text Available To investigate the cholesterol-lowering effects of alfalfa saponin extract (ASE and its regulation mechanism on some key genes involved in cholesterol metabolism, 40 healthy 7 weeks old male Sprague Dawley (SD rats were randomly divided into four groups with 10 rats in each group: control group, hyperlipidemic group, ASE treatment group, ASE prevention group. The body weight gain, relative liver weight and serum lipid 1evels of rats were determined. Total cholesterol (TC and total bile acids (TBA levels in liver and feces were also measured. Furthermore, the activity and mRNA expressions of Hmgcr, Acat2, Cyp7a1 and Ldlr were investigated. The results showed the following: (1 The abnormal serum lipid levels in hyperlipidemic rats were ameliorated by ASE administration (both ASE prevention group and treatment group (P<0.05. (2 Both ASE administration to hyperlipidemic rats significantly reduced liver TC and increased liver TBA level (P<0.05. TC and TBA levels in feces of hyperlipidemic rats were remarkably elevated by both ASE administration (P<0.05. (3 mRNA expressions of Hmgcr and Acat2 in the liver of hyperlipidemic rats were remarkably down-regulated (P<0.05, as well as mRNA expressions of Cyp7a1 and Ldlr were dramatically up-regulated by both ASE administration (P<0.05. The activities of these enzymes also paralleled the observed changes in mRNA levels. (4 There was no significant difference between ASE treatment and ASE prevention group for most parameters evaluated. Our present study indicated that ASE had cholesterol-lowering effects. The possible mechanism could be attributed to (1 the down-regulation of Hmgcr and Acat2, as well as up-regulation of Cyp7a1 and Ldlr in the liver of hyperlipidemic rats, which was involved in cholesterol biosynthesis, uptake, and efflux pathway; (2 the increase in excretion of cholesterol. The findings in our study suggested ASE had great potential usefulness as a natural agent for treating hyperlipidemia.

  5. Sor/88-114, 25 February 1988, Atomic Energy Control Regulations, amendment

    International Nuclear Information System (INIS)

    1988-01-01

    The amendments to the Regulations mainly concern naturally-occurring radioactive prescribed substances (namely, uranium, thorium, radium, etc.). Any naturally-occurring radioactive material in a mineral or other material which has not been related to an activity associated with the development, application or use of atomic energy, is exempted from the scope of the Regulations. The Regulations will therefore not apply to radioactive substances such as uranium or thorium present in building materials or in minerals commonly used in industrial activities which are not associated with the nuclear fuel cycle. This exemption does not apply to such material in connection with import control and preparation for transport [fr

  6. The legal regime governing the peaceful uses of nuclear energy. II. International Regulations. Pt.1. Regulations on peaceful uses

    International Nuclear Information System (INIS)

    1979-12-01

    The first volume on atomic energy law published by CNEN reproduced national laws and regulations in that field. This book constitutes part one of the second volume and deals with international nuclear conventions and cooperation as at 30 June 1978. It reproduces the instruments and conventions which set up the international nuclear agencies, recommendations in the field of radiation protection and nuclear safety, the nuclear third party liability conventions, the international instruments concerning technical and scientific cooperation and finally, the bilateral cooperation agreements between Italy and other nations and its agreements with international organizations (NEA) [fr

  7. Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.

    Science.gov (United States)

    Huang, Xiao X; McCaughan, Geoffrey W; Shackel, Nicholas A; Gorrell, Mark D

    2007-09-01

    Cirrhosis can lead to hepatocellular carcinoma (HCC). Non-diseased liver and hepatitis C virus (HCV)-associated cirrhosis with or without HCC were compared. Proliferation pathway genes, immune response genes and oncogenes were analysed by a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining. Real-time RT-PCR showed up-regulation of genes in HCV cirrhosis including the proliferation-associated genes bone morphogenetic protein 3 (BMP3), placental growth factor 3 (PGF3), vascular endothelial growth factor receptor 1 (VEGFR1) and soluble VEGFR1, the oncogene FYN, and the immune response-associated genes toll-like receptor 9 (TLR9) and natural killer cell transcript 4 (NK4). Expressions of TLR2 and the oncogenes B-cell CLL/lymphoma 9 (BCL9) and PIM2 were decreased in HCV cirrhosis. In addition, PIM2 and TLR2 were increased in HCV cirrhosis with HCC compared with HCV cirrhosis. The ligand/receptor pair PGF and VEGFR1 was intensely expressed by the portal tract vascular endothelium. VEGFR1 was expressed in reactive biliary epithelial structures in fibrotic septum and in some stellate cells and macrophages. PGF and VEGFR1 may have an important role in the pathogenesis of the neovascular response in cirrhosis.

  8. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

    Science.gov (United States)

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

  9. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Saidan Ding

    2017-09-01

    Full Text Available Insulin-like growth factor I (IGF-I has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE was shown to be induced by elevated intracranial dopamine (DA. The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95 and neuronal nitric oxide synthase (nNOS was found in neurons. Ribosomal S6 protein kinase (RSK phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2. In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE.

  10. Waterborne gemfibrozil challenges the hepatic antioxidant defense system and down-regulates peroxisome proliferator-activated receptor beta (PPARβ) mRNA levels in male goldfish (Carassius auratus)

    International Nuclear Information System (INIS)

    Mimeault, C.; Trudeau, V.L.; Moon, T.W.

    2006-01-01

    The lipid regulator gemfibrozil (GEM) is one of many human pharmaceuticals found in the aquatic environment. We previously demonstrated that GEM bioconcentrates in blood and reduces plasma testosterone levels in goldfish (Carassius auratus). In this study, we address the potential of an environmentally relevant waterborne concentration of GEM (1.5 μg/l) to induce oxidative stress in goldfish liver and whether this may be linked to GEM acting as a peroxisome proliferator (PP). We also investigate the autoregulation of the peroxisome proliferator-activated receptors (PPARs) as a potential index of exposure. The three PPAR subtypes (α, β, and γ) were amplified from goldfish liver cDNA. Goldfish exposed to a concentration higher (1500 μg/l) than environmentally relevant for 14 and 28 days significantly reduce hepatic PPARβ mRNA levels (p < 0.001). Levels of CYP1A1 mRNA were unchanged. GEM exposure significantly induced the antioxidant defense enzymes catalase (p < 0.001), glutathione peroxidase (p < 0.001) and glutathione-S-transferase (p = 0.006) but not acyl-CoA oxidase or glutathione reductase. As GEM exposure failed to increase levels of thiobarbituric reactive substances (TBARS), we conclude that a sub-chronic exposure to GEM upregulates the antioxidant defense status of the goldfish as an adaptive response to this human pharmaceutical

  11. A method for regulating strong nonlinear vibration energy of the flexible arm

    Directory of Open Access Journals (Sweden)

    Yushu Bian

    2015-07-01

    Full Text Available For an oscillating system, large amplitude indicates strong vibration energy. In this article, modal interaction is used as a useful means to regulate strong nonlinear vibration energy of the flexible arm undergoing rigid motion. A method is put forward to migrate and dissipate vibration energy based on modal interaction. By means of multiple-scale perturbation analysis, it is proven that internal resonance can be successfully established between modes of the flexible arm and the vibration absorber. Through examples and analyses, it is verified that this control method is effective in regulating strong vibration energy and can be used to suppress strong nonlinear vibration of the flexible arm undergoing rigid motion.

  12. Energy efficiency optimization in distribution transformers considering Spanish distribution regulation policy

    International Nuclear Information System (INIS)

    Pezzini, Paola; Gomis-Bellmunt, Oriol; Frau-Valenti, Joan; Sudria-Andreu, Antoni

    2010-01-01

    In transmission and distribution systems, the high number of installed transformers, a loss source in networks, suggests a good potential for energy savings. This paper presents how the Spanish Distribution regulation policy, Royal Decree 222/2008, affects the overall energy efficiency in distribution transformers. The objective of a utility is the maximization of the benefit, and in case of failures, to install a chosen transformer in order to maximize the profit. Here, a novel method to optimize energy efficiency, considering the constraints set by the Spanish Distribution regulation policy, is presented; its aim is to achieve the objectives of the utility when installing new transformers. The overall energy efficiency increase is a clear result that can help in meeting the requirements of European environmental plans, such as the '20-20-20' action plan.

  13. Energy efficiency optimization in distribution transformers considering Spanish distribution regulation policy

    Energy Technology Data Exchange (ETDEWEB)

    Pezzini, Paola [Centre d' Innovacio en Convertidors Estatics i Accionaments (CITCEA-UPC), E.T.S. Enginyeria Industrial Barcelona, Universitat Politecnica Catalunya, Diagonal, 647, Pl. 2, 08028 Barcelona (Spain); Gomis-Bellmunt, Oriol; Sudria-Andreu, Antoni [Centre d' Innovacio en Convertidors Estatics i Accionaments (CITCEA-UPC), E.T.S. Enginyeria Industrial Barcelona, Universitat Politecnica Catalunya, Diagonal, 647, Pl. 2, 08028 Barcelona (Spain); IREC Catalonia Institute for Energy Research, Josep Pla, B2, Pl. Baixa, 08019 Barcelona (Spain); Frau-Valenti, Joan [ENDESA, Carrer Joan Maragall, 16 07006 Palma (Spain)

    2010-12-15

    In transmission and distribution systems, the high number of installed transformers, a loss source in networks, suggests a good potential for energy savings. This paper presents how the Spanish Distribution regulation policy, Royal Decree 222/2008, affects the overall energy efficiency in distribution transformers. The objective of a utility is the maximization of the benefit, and in case of failures, to install a chosen transformer in order to maximize the profit. Here, a novel method to optimize energy efficiency, considering the constraints set by the Spanish Distribution regulation policy, is presented; its aim is to achieve the objectives of the utility when installing new transformers. The overall energy efficiency increase is a clear result that can help in meeting the requirements of European environmental plans, such as the '20-20-20' action plan. (author)

  14. The radioactive waste regulation in the new Czech Nuclear Energy Act

    International Nuclear Information System (INIS)

    Kucerka, M.

    1995-01-01

    Recently, in the Czech Republic, there is in the phase of development the Act on Peaceful Use of Nuclear Energy and Ionizing Radiation, so called the Nuclear Energy Act. This Act has to replace existing regulations and fulfill some not yet covered fields of that area. The act is developed as so called ''umbrella act'' and has to cover all aspects of the nuclear energy and ionizing radiation use, from uranium mining or isotopes use in medicine, to the power generation in nuclear power plants. It will include among others also provisions on registration and licensing, liability for nuclear damage, decommissioning and radioactive waste management funding, and some other topics, that were missing in the regulations up to today. The paper describes recent state policy in the field of radioactive waste management and the main provisions of proposed Nuclear Energy Act, concerning the radioactive waste management

  15. Hypothalamic roles of mTOR complex I: Integration of nutrient and hormone signals to regulate energy homeostasis

    Science.gov (United States)

    Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight...

  16. Quota regulation as energy political tool. Feasibility study; Kvoteregulering som energipolitisk virkemiddel. Konsekevensanalysen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-06-15

    The overall aim of the project was to determine what effect the energy policy introduced through the law on CO{sub 2}-quotas would have on the development the energy sector in Denmark. The energy policy is a market-based approach where the individual stakeholders choose how they will react within the boundaries of the allocated quotas. Options include the purchasing of quotas on the open market, investment in CDM/JI activities, the implementation of energy efficiency initiatives or fuel substitution. The focus of the study was on how the affected companies reacted to the implementation of a CO{sub 2}-quota. This was done by undertaking a series of interviews that resulted in a stakeholder analysis of companies encompassed by the CO2-quota law. A series of national consequences of the law on CO{sub 2}-quotas were then determined based on the stakeholder analysis. According to the results of the stakeholder analysis the following consequences were determined for the periods 2005-2007 and 2008-2012 as a result of quota regulation: 1) In the electricity sector no additional investments will be made in energy efficiency initiatives or fuel substitution projects than were already planned before quota regulation was introduced. 2) The heating sector will carry out isolated energy efficiency projects, but generally these are not socio-economically viable. 3) Industry will carry out isolated energy efficiency initiatives and renewable energy projects. Only 1.2 million tonnes of CO{sub 2} will be reduced annually through these initiatives compared to the estimated annual shortfall of 8 13 million tonnes CO{sub 2}. The shortfall will be made up through the purchase of quotas on the open market. This study indicates, therefore, that quota regulation will make a limited contribution to further initiatives in energy efficiency and renewable energy. If further energy efficiency initiatives are desired it will be necessary to implement other regulatory incentives. With regards to

  17. Effect of 24-h severe energy restriction on appetite regulation and ad libitum energy intake in lean men and women.

    Science.gov (United States)

    Clayton, David J; Burrell, Kirsty; Mynott, Georgina; Creese, Mark; Skidmore, Nicola; Stensel, David J; James, Lewis J

    2016-12-01

    Intermittent severe energy restriction (SER) can induce substantial weight loss, but the appetite regulatory responses to SER are unknown and may dictate long-term dietary adherence. We determined the effect of 24-h SER on appetite regulation, metabolism, and energy intake. Eighteen lean men and women completed two 3-d trials in randomized, counterbalanced order. On day 1 subjects consumed standardized diets containing 100% (mean ± SD: 9.3 ± 1.3 MJ; energy balance) or 25% [2.3 ± 0.3 MJ; energy restriction (ER)] of energy requirements. On day 2, a standardized breakfast was consumed, with plasma concentrations of acylated ghrelin, glucagon-like peptide 1, insulin, glucose, and nonesterified fatty acids determined for 4 h. Ad libitum energy intake was assessed at lunch and dinner with subjective appetite and resting metabolism assessed throughout. On day 3, ad libitum energy intake was assessed at breakfast and by weighed food records. Energy intake was 7% greater on day 2 (P 0.145). During ER, postprandial concentrations of acylated ghrelin were lower (P < 0.05), whereas glucose (P < 0.05) and nonesterified fatty acids (P < 0.0001) were higher. Postprandial glucagon-like peptide 1 7-36 (P = 0.784) and insulin (P = 0.06) concentrations were not significantly different between trials. Energy expenditure was lower during ER in the morning (P < 0.01). In lean young adults, 24-h SER transiently elevated subjective appetite and marginally increased energy intake, but hormonal appetite markers did not respond in a manner indicative of hyperphagia. These results suggest that intermittent SER might be useful to attenuate energy intake and control body weight in this population. This trial was registered at www.clinicaltrials.gov.uk as NCT02696772. © 2016 American Society for Nutrition.

  18. Duodenal-jejunal bypass surgery up-regulates the expression of the hepatic insulin signaling proteins and the key regulatory enzymes of intestinal gluconeogenesis in diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Sun, Dong; Wang, Kexin; Yan, Zhibo; Zhang, Guangyong; Liu, Shaozhuang; Liu, Fengjun; Hu, Chunxiao; Hu, Sanyuan

    2013-11-01

    Duodenal-jejunal bypass (DJB), which is not routinely applied in metabolic surgery, is an effective surgical procedure in terms of type 2 diabetes mellitus resolution. However, the underlying mechanisms are still undefined. Our aim was to investigate the diabetic improvement by DJB and to explore the changes in hepatic insulin signaling proteins and regulatory enzymes of gluconeogenesis after DJB in a non-obese diabetic rat model. Sixteen adult male Goto-Kakizaki rats were randomly divided into DJB and sham-operated groups. The body weight, food intake, hormone levels, and glucose metabolism were measured. The levels of protein expression and phosphorylation of insulin receptor-beta (IR-β) and insulin receptor substrate 2 (IRS-2) were evaluated in the liver. We also detected the expression of key regulatory enzymes of gluconeogenesis [phosphoenoylpyruvate carboxykinase-1 (PCK1), glucose-6-phosphatase-alpha (G6Pase-α)] in small intestine and liver. DJB induced significant diabetic improvement with higher postprandial glucagons-like peptide 1, peptide YY, and insulin levels, but without weight loss. The DJB group exhibited increased expression and phosphorylation of IR-β and IRS-2 in liver, up-regulated the expression of PCK1 and G6Pase-α in small intestine, and down-regulated the expression of these enzymes in liver. DJB is effective in up-regulating the expression of the key proteins in the hepatic insulin signaling pathway and the key regulatory enzymes of intestinal gluconeogenesis and down-regulating the expression of the key regulatory enzymes of hepatic gluconeogenesis without weight loss. Our study helps to reveal the potential role of hepatic insulin signaling pathway and intestinal gluconeogenesis in ameliorating insulin resistance after metabolic surgery.

  19. Developmental programming of energy balance regulation: is physical activity more 'programmable' than food intake?

    Science.gov (United States)

    Zhu, Shaoyu; Eclarinal, Jesse; Baker, Maria S; Li, Ge; Waterland, Robert A

    2016-02-01

    Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catch-up growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sex-specific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life

  20. Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells.

    Science.gov (United States)

    Lee, Jin-Ching; Tseng, Chin-Kai; Young, Kung-Chia; Sun, Hung-Yu; Wang, Shainn-Wei; Chen, Wei-Chun; Lin, Chun-Kuang; Wu, Yu-Hsuan

    2014-01-01

    This study aimed to evaluate the anti-hepatitis C virus (HCV) activity of andrographolide, a diterpenoid lactone extracted from Andrographis paniculata, and to identify the signalling pathway involved in its antiviral action. Using HCV replicon and HCVcc infectious systems, we identified anti-HCV activity of andrographolide by measuring protein and RNA levels. A reporter activity assay was used to determine transcriptional regulation of anti-HCV agents. A specific inhibitor and short hairpin RNAs were used to investigate the mechanism responsible for the effect of andrographolide on HCV replication. In HCV replicon and HCVcc infectious systems, andrographolide time- and dose-dependently suppressed HCV replication. When combined with IFN-α, an inhibitor targeting HCV NS3/4A protease (telaprevir), or NS5B polymerase (PSI-7977), andrographolide exhibited a significant synergistic effect. Andrographolide up-regulated the expression of haeme oxygenase-1 (HO-1), leading to increased amounts of its metabolite biliverdin, which was found to suppress HCV replication by promoting the antiviral IFN responses and inhibiting NS3/4A protease activity. Significantly, these antiviral effects were attenuated by an HO-1-specific inhibitor or HO-1 gene knockdown, indicating that HO-1 contributed to the anti-HCV activity of andrographolide. Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated HO-1 expression, and this was found to be associated with its anti-HCV activity. Our results demonstrate that andrographolide has the potential to control HCV replication and suggest that targeting the Nrf2-HO-1 signalling pathway might be a promising strategy for drug development. © 2013 The British Pharmacological Society.

  1. Separation of hepatic iron and fat by dual-source dual-energy computed tomography based on material decomposition: an animal study.

    Science.gov (United States)

    Ma, Jing; Song, Zhi-Qiang; Yan, Fu-Hua

    2014-01-01

    To explore the feasibility of dual-source dual-energy computed tomography (DSDECT) for hepatic iron and fat separation in vivo. All of the procedures in this study were approved by the Research Animal Resource Center of Shanghai Ruijin Hospital. Sixty rats that underwent DECT scanning were divided into the normal group, fatty liver group, liver iron group, and coexisting liver iron and fat group, according to Prussian blue and HE staining. The data for each group were reconstructed and post-processed by an iron-specific, three-material decomposition algorithm. The iron enhancement value and the virtual non-iron contrast value, which indicated overloaded liver iron and residual liver tissue, respectively, were measured. Spearman's correlation and one-way analysis of variance (ANOVA) were performed, respectively, to analyze statistically the correlations with the histopathological results and differences among groups. The iron enhancement values were positively correlated with the iron pathology grading (r = 0.729, pVNC) values were negatively correlated with the fat pathology grading (r = -0.642,pVNC values (F = 25.308,pVNC values were only observed between the fat-present and fat-absent groups. Separation of hepatic iron and fat by dual energy material decomposition in vivo was feasible, even when they coexisted.

  2. Regulation of mouse hepatic CYP2D9 mRNA expression by growth and adrenal hormones.

    Science.gov (United States)

    Jarukamjorn, Kanokwan; Sakuma, Tsutomu; Jaruchotikamol, Atika; Oguro, Miki; Nemoto, Nobuo

    2006-02-01

    The constitutive expression of CYP2D9 is sexually dimorphic, namely, strong in males, but diminutive in females. Repetition of mimic growth hormone (GH) secretion pattern impressively returned the mRNA expression level to that in intact mice: the GH secretion pattern's regulation of CYP2D9 mRNA expression has been predominantly disrupted by exogenous GH-administration. The extensive decline of CYP2D9 mRNA expression becoming a sexually non-specific P450 in 9-week-old male mice exposed as neonates to monosodium L-glutamate (MSG) suggested that the male GH secretion pattern is a key to the regulation of male-specific CYP2D9 mRNA expression in adult mice. Dexamethasone (Dex) showed possibility to induce CYP2D9 mRNA expression in adult MSG-neonatally treated mice of either sex. However, the antagonism was observed by co-administration of Dex and GH in the males. Dex-administration in adrenalectomized mice significantly elevated CYP2D9 mRNA expression levels. These findings suggest that an adrenal hormone participates in the regulatory mechanism of CYP2D9 mRNA expression in association with GH.

  3. Alcoholic Hepatitis

    Science.gov (United States)

    ... yellow color. Confusion, drowsiness and slurred speech (hepatic encephalopathy). A damaged liver has trouble removing toxins from your body. The ... of toxins can damage your brain. Severe hepatic encephalopathy can result in ... of the liver frequently leads to liver failure. Kidney failure. A ...

  4. CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

    NARCIS (Netherlands)

    Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

  5. Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

    DEFF Research Database (Denmark)

    Meidtner, Karina; Fisher, Eva; Angquist, Lars

    2014-01-01

    We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI...

  6. [Low-molecular-weight regulators of biogenic polyamine metabolism affect cytokine production and expression of hepatitis С virus proteins in Huh7.5 human hepatocarcinoma cells].

    Science.gov (United States)

    Masalova, O V; Lesnova, E I; Samokhvalov, E I; Permyakova, K Yu; Ivanov, A V; Kochetkov, S N; Kushch, A A

    2017-01-01

    Hepatitis C virus (HCV) induces the expression of the genes of proinflammatory cytokines, the excessive production of which may cause cell death, and contribute to development of liver fibrosis and hepatocarcinoma. The relationship between cytokine production and metabolic disorders in HCV-infected cells remains obscure. The levels of biogenic polyamines, spermine, spermidine, and their precursor putrescine, may be a potential regulator of these processes. The purpose of the present work was to study the effects of the compounds which modulate biogenic polyamines metabolism on cytokine production and HCV proteins expression. Human hepatocarcinoma Huh7.5 cells have been transfected with the plasmids that encode HCV proteins and further incubated with the following low-molecular compounds that affect different stages of polyamine metabolism: (1) difluoromethylornithine (DFMO), the inhibitor of ornithine decarboxylase, the enzyme that catalyzes the biosynthesis of polyamines; (2) N,N'-bis(2,3-butane dienyl)-1,4-diaminobutane (MDL72.527), the inhibitor of proteins involved in polyamine degradation; and (3) synthetic polyamine analog N^(I),N^(II)-diethylnorspermine (DENSpm), an inducer of polyamine degradation enzyme. The intracellular accumulation and secretion of cytokines (IL-6, IL-1β, TNF-α, and TGF-β) was assessed by immunocytochemistry and in the immunoenzyme assay, while the cytokine gene expression was studied using reverse transcription and PCR. The effects of the compounds under analysis on the expression of HCV proteins were analyzed using the indirect immunofluorescence with anti-HCV monoclonal antibodies. It has been demonstrated that, in cells transfected with HCV genes, DFMO reduces the production of three out of four tested cytokines, namely, TNF-α and TGF-β in cells that express HCV core, Е1Е2, NS3, NS5A, and NS5B proteins, and IL-1β in the cells that express HCV core, Е1Е2, and NS3 proteins. MDL72527 and DENSpm decreased cytokine production

  7. Commission de regulation de l'energie. Activity report june 2007

    International Nuclear Information System (INIS)

    2007-06-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2007 activity report of CRE. Content: A - Towards a single European energy market: Birth of a single European energy market (Origins of Europe of Energy, Emergence of a European energy policy); Main European Community guiding lines (European governance as regards energy, Guiding principles for the internal energy market); European Community activities (European Commission reports, Electricity and gas Regional Initiatives); Organisation and coordination of European regulators (Joint organisation of European regulators, CRE's relations with European Community institutions); CRE's European activities (Regional integration of gas markets, Regional integration of electricity markets, Operation of the European interconnected electricity grid and security of supply, CRE's other European activities); B - CRE action at national level: Grids/networks and infrastructures (General information, Electricity grids, Regulation of gas networks and infrastructures); Markets (Changes in the regulatory and legislative contexts of electricity and natural gas markets, Electricity markets

  8. Energy abatement in Chinese industry: Cost evaluation of regulation strategies and allocation alternatives

    International Nuclear Information System (INIS)

    Xia, X.H.; Chen, G.Q.

    2012-01-01

    For Chinese industry, the costs of different energy consumption abatement scenarios are evaluated by the method of directional distance function. These scenarios are based on the combinations of regulation strategies and allocation alternatives—the former are sectors and provinces, and the latter include the five principles of average, intensity share, absolute share, discriminatory absolute and discriminatory intensity. For all the scenarios, the quantitative impacts in terms of output potential loss are calculated and compared. Due to less output potential loss for all the allocation alternatives, the sector regulation strategy is shown to be more effective than the province regulation strategy. It is also demonstrated that, among all the scenarios considered, the sector regulation based on the intensity share principle and the province regulation based on the absolute share principle are the two optimal. The performances of energy abatement allocation of the 11th and 12th Five Year Plans of China are assessed against the simulated scenarios. - Highlights: ► The costs of different energy consumption abatement scenarios are evaluated for Chinese industry. ► The impacts on all entities under all allocation alternatives are calculated and compared. ► The optimal scenarios for the different strategies are identified. ► The performances of the 11th and 12th Five Year Plans are assessed.

  9. Control and distribution of electrical energy as mirrored by the relevant VDE regulations

    Energy Technology Data Exchange (ETDEWEB)

    Becker, E [Metzenauer und Jung G.m.b.H., Wuppertal (Germany, F.R.)

    1977-01-01

    The essay deals with the regulations issued by the VDE in the fields of electrical energy distribution and control on national and international level. Starting from an interesting historical survey the author deals with VDE stipulations, introduces new control systems and explains the latest switching units.

  10. 75 FR 44276 - Bureau of Ocean Energy Management, Regulation, and Enforcement (BOEMRE); Cancellation of Oil and...

    Science.gov (United States)

    2010-07-28

    ... (OCS) in the Gulf of Mexico (GOM) AGENCY: Bureau of Ocean Energy Management, Regulation, and Enforcement, Interior. ACTION: Cancellation of WPA Gulf of Mexico Lease Sale 215. SUMMARY: On May 27, 2010, the President announced the Secretary of the Interior's decision to cancel WPA Sale 215 that was...

  11. Control mechanisms for battery energy storage system performing primary frequency regulation and self-consumption optimization

    NARCIS (Netherlands)

    Pliatskas Stylianidis, A.

    2016-01-01

    This report contains the design of a model for the integration of a battery energy system in a household level and its use for primary frequency regulation and self-consumption optimization. The main goal of this project was to investigate what are the possible applications and the most suitable for

  12. Serotonin 2c receptors in pro-opiomelanocortin neurons regulate energy and glucose homeostasis

    Science.gov (United States)

    Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors are attractive pharmacological targets for the treatment of obesity; however, the identity of the serotonin 2C receptor-expressing neurons that mediate the effects of serotonin and serotonin 2C receptor a...

  13. Endogenous monitoring: a new challenge for the regulation of energy externalities

    International Nuclear Information System (INIS)

    Millock, K.

    1999-11-01

    The present article studies the problem of regulating externalities from energy use, with particular emphasis on the problem of information. A standard economics. The article shows how the optimal choice of instruments used to regulate the externalities from energy use will change with the more widespread adoption of modern monitoring technologies. We will illustrate how the application of incentive policies conditioned on monitoring can contribute to the implementation of flexible mechanisms for greenhouse gas abatement. Section 2 briefly summarises the economic framework for the regulation of externalities resulting from energy use. In Section 3, an illustrative model is presented in which the introduction of monitoring of emissions is endogenous and conditions the best type of instrument used by the regulator to internalize the externalities from energy use. Section 4 then examines the implications of this framework for the application of the flexible incentives introduced in the Kyoto Protocol. It shows how the success of project-based approaches, such as Joint Implementation and the Clean Development Mechanism, depends upon the implementation of appropriate incentives for monitoring. Section 5 concludes. (author)

  14. MicroRNA Regulation of Brown Adipogenesis and Thermogenic Energy Expenditure

    DEFF Research Database (Denmark)

    Shamsi, Farnaz; Zhang, Hongbin; Tseng, Yu-Hua

    2017-01-01

    Obesity, diabetes, and associated metabolic diseases have become global epidemics. Obesity results from excess accumulation of white fat, while brown and its related beige fat function to dissipate energy as heat, thus counteracting obesity and its related metabolic disorders. Understanding...... attracted a great deal of research interests in exploring their roles in physiological and pathophysiological conditions. This review focuses on the recent advances of regulating brown adipogenesis and energy metabolism by miRNAs, aiming to delineate the regulatory principles of miRNAs on this unique aspect...... of energy homeostasis....

  15. Decree 831/976 Industry and Energy Ministry approve an organic regulation

    International Nuclear Information System (INIS)

    1976-01-01

    The ordinance 831 of 1976 approve the organic regulation of the Ministry of Industry and Energy and organization manuals and functions according to the principle and elaborated technical approaches and systematized by the National Office of the Civil Service. Among some of their made they are projecting the industrial politics and energetics of the country exercising supervision and control, as well as the development of the industry and diverse energy sources, to propitiate the use of the atomic energy in the Uruguay coordinating the activities that are carried out

  16. Commission de regulation de l'energie. Activity Report 2009

    International Nuclear Information System (INIS)

    2010-01-01

    CRE is the French commission for energy regulation. CRE's remit is to assist in ensuring the proper operation of the electricity and natural gas markets for the benefit of the end-user. In particular, CRE ensures that the conditions of access to electricity and natural gas transmission and distribution systems do not hinder the development of competition. It monitors, for the electricity and natural gas sectors, all transactions made between suppliers, traders and producers, all transactions made on the organised markets and cross-border trading. It ensures that suppliers, traders and producers propose offers that are consistent with their financial and technical constraints. It monitors the implementation of and compliance with regulations giving consumers the right to choose their supplier in a competitive market, and allowing new suppliers to enter the market. This document is the 2009 activity report of CRE. Content: A - How the CRE works and the activity of the CoRDiS; B - Implementation of the third energy package will strengthen regulation in this sector; C - The regulator contributes to the correct operation of the infrastructures, the interconnection of European grids and security of supplies; D - Regulation: serving investment and quality; E - Renewable energy, advanced metering systems and the grids of the future are all priority means of delivering sustainable development; F - The CRE is contributing to the smooth operation of electricity and gas markets to the benefit of consumers; G - Appendices: 1. Summary of the principal deliberations of the CRE; 2. European and international calendar for 2009; 3. Council of European Energy Regulators (CEER); 4. Glossary; 5. Acronyms; 6. Units and conversions; 7. Index; 8. List of boxes, figures and tables

  17. Leading trends in environmental regulation that affect energy development. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Steele, R V; Attaway, L D; Christerson, J A; Kikel, D A; Kuebler, J D; Lupatkin, B M; Liu, C S; Meyer, R; Peyton, T O; Sussin, M H

    1980-01-01

    Major environmental issues that are likely to affect the implementation of energy technologies between now and the year 2000 are identified and assessed. The energy technologies specifically addressed are: oil recovery and processing; gas recovery and processing; coal liquefaction; coal gasification (surface); in situ coal gasification; direct coal combustion; advanced power systems; magnetohydrodynamics; surface oil shale retorting; true and modified in situ oil shale retorting; geothermal energy; biomass energy conversion; and nuclear power (fission). Environmental analyses of these technologies included, in addition to the main processing steps, the complete fuel cycle from resource extraction to end use. A comprehensive survey of the environmental community (including environmental groups, researchers, and regulatory agencies) was carried out in parallel with an analysis of the technologies to identify important future environmental issues. Each of the final 20 issues selected by the project staff has the following common attributes: consensus of the environmental community that the issue is important; it is a likely candidate for future regulatory action; it deals with a major environmental aspect of energy development. The analyses of the 20 major issues address their environmental problem areas, current regulatory status, and the impact of future regulations. These analyses are followed by a quantitative assessment of the impact on energy costs and nationwide pollutant emissions of possible future regulations. This is accomplished by employing the Strategic Environmental Assessment System (SEAS) for a subset of the 20 major issues. The report concludes with a more general discussion of the impact of environmental regulatory action on energy development.

  18. A Perspective of Energy Codes and Regulations for the Buildings of the Future

    Energy Technology Data Exchange (ETDEWEB)

    Rosenberg, Michael [Pacific Northwest National Laboratory,2032 Todd Street,Eugene, OR 97405e-mail: michael.rosenberg@pnnl.gov; Jonlin, Duane [Seattle Department ofConstruction and Inspections,P.O. Box 34019,Seattle, WA 98124e-mail: duane.jonlin@seattle.gov; Nadel, Steven [American Council for anEnergy-Efficient Economy,529 14th Street NW #600,Washington, DC 20045e-mail: snadel@aceee.org

    2016-10-13

    Today’s building energy codes focus on prescriptive requirements for features of buildings that are directly controlled by the design and construction teams and verifiable by municipal inspectors. Although these code requirements have had a significant impact, they fail to influence a large slice of the building energy use pie – including not only miscellaneous plug loads, cooking equipment and commercial/industrial processes, but the maintenance and optimization of the code-mandated systems as well. Currently, code compliance is verified only through the end of construction, and there are no limits or consequences for the actual energy use in an occupied building. In the future, our suite of energy regulations will likely expand to include building efficiency, energy use or carbon emission budgets over their full life cycle. Intelligent building systems, extensive renewable energy, and a transition from fossil fuel to electric heating systems will likely be required to meet ultra-low-energy targets. This paper lays out the authors’ perspectives on how buildings may evolve over the course of the 21st century and the roles that codes and regulations will play in shaping those buildings of the future.

  19. Energy-economy relationship and environmental regulation in the presence of unrecorded economy

    International Nuclear Information System (INIS)

    Karanfil, F.

    2008-12-01

    This PhD thesis including five manuscripts and a brief international comparison analysis proposes a multi-field study on the economic and environmental effects of energy consumption. It first investigates the causal relationship between economic growth and energy consumption in Turkey and then offers a new methodology for the estimation of unrecorded economy based on environmental data. The thesis develops also asymmetric information models, where the regulator does not know the true emission level of each firm that it wishes to regulate, so as to examine to what extend different enforcement mechanisms affect incentives for the firms to reduce polluting emissions and to invest in clean energy technologies. In order to provide a complete insight on the effects of both fiscal and environmental enforcement policies, some similar analysis are conducted taking into account the existence of unrecorded economy. The results in this thesis essentially show that: first, energy conservation policies can be implemented in order to reduce greenhouse gas emissions without any adverse effect on the recorded economic activities; second, different audit mechanisms should be used depending on the environmental objective of the enforcement agency; third, in some cases, environmental regulations may increase the size of unrecorded economy; fourth, economic policies to combat unrecorded economy may not serve as a complement to energy conservation policies. (author)

  20. Lessons learned implementing environmental regulations at non-Department of Energy sites

    International Nuclear Information System (INIS)

    Craig, R.B.; Dippo, G.L.

    1991-01-01

    The Hazardous Waste Remedial Actions Program (HAZWRAP) has been involved in the implementation of environmental regulations at non-Department of Energy (DOE) facilities for > 5 years. If any common thread has been identified in working at these sites, it is that no two sites can be treated the same. Each site and its associated wastes, governing regulations, and environmental conditions are different. The list of technical lessons learned is long, and their applicability to other sites must be looked at for each specific case. That is far too large a task to undertake here. The most important lesson HAZWRAP learned is not technical. Implementing environmental regulations at non-DOE sites is not any different from implementing regulations or anything else done at DOE facilities. The key to success lies in quality, planning, and communication. Taking the time to implement a good quality program based on sound planning and open communication will ensure program success

  1. Control of 2D Flexible Structures by Confinement of Vibrations and Regulation of Their Energy Flow

    Directory of Open Access Journals (Sweden)

    Fakhreddine Landolsi

    2009-01-01

    Full Text Available In this paper, we investigate the control of 2D flexible structures by vibration confinement and the regulation of their energy flow along prespecified spatial paths. A discretized-model-based feedback strategy, aiming at confining and suppressing simultaneously the vibration, is proposed. It is assumed that the structure consists of parts that are sensitive to vibrations. The control design introduces a new pseudo-modal matrix derived from the computed eigenvectors of the discretized model. Simulations are presented to show the efficacy of the proposed control law. A parametric study is carried out to examine the effects of the different control parameters on the simultaneous confinement and suppression of vibrations. In addition, we conducted a set of simulations to investigate the flow control of vibrational energy during the confinement-suppression process. We found that the energy flow can be regulated via a set of control parameters for different confinement configurations.

  2. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Science.gov (United States)

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

    2011-01-11

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  3. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2011-01-01

    Full Text Available Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  4. Operation of Grid -Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Loan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2017-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  5. Suggested Operation Grid-Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Ioan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2015-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  6. Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.

    Science.gov (United States)

    Nordström, Viola; Willershäuser, Monja; Herzer, Silke; Rozman, Jan; von Bohlen Und Halbach, Oliver; Meldner, Sascha; Rothermel, Ulrike; Kaden, Sylvia; Roth, Fabian C; Waldeck, Clemens; Gretz, Norbert; de Angelis, Martin Hrabě; Draguhn, Andreas; Klingenspor, Martin; Gröne, Hermann-Josef; Jennemann, Richard

    2013-01-01

    Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis.

  7. Hepatitis B Virus X Protein Up-Regulates AKR1C1 Expression Through Nuclear Factor-Y in Human Hepatocarcinoma Cells.

    Science.gov (United States)

    Li, Kai; Ding, Shijia; Chen, Ke; Qin, Dongdong; Qu, Jialin; Wang, Sen; Sheng, Yanrui; Zou, Chengcheng; Chen, Limin; Tang, Hua

    2013-01-01

    The hepatitis B virus X (HBx) protein has long been recognized as an important transcriptional transactivator of several genes. Human aldo-keto reductase family 1, member C1 (AKR1C1), a member of the family of AKR1CS, is significantly increased in HBx-expressed cells. This study aimed to investigate the possible mechanism of HBx in regulating AKR1C1 expression in HepG2.2.15 cells and the role of AKR1C1 for HBV-induced HCC. RT-PCR was performed to detect AKR1C1 expression on mRNA level in HepG2 and HepG2.2.15 cell. The promoter activity of AKR1C1 was assayed by transient transfection and Dual-luciferase reporter assay system. The AKR1C1 promoter sequence was screened using the TFSEARCH database and the ALIBABA 2.0 software. The potential transcription factors binding sites were identified using 5' functional deletion analysis and site-directed mutagenesis. In this study, we found that HBx promoted AKR1C1 expression in HepG2.2.15 cells. Knockdown of HBx inhibited AKR1C1 activation. The role of HBx expression in regulating the promoter activity of human AKR1C1 gene was analyzed. The 5'functional deletion analysis identified that the region between -128 and -88 was the minimal promoter region of HBx to activate AKR1C1 gene expression. Site-directed mutagenesis studies suggested that nuclear factor-Y (NF-Y) plays an important role in this HBx-induced AKR1C1 activation. In HepG2.2.1.5 cell, HBx can promote AKR1C1 promoter activity and thus activates the basal transcription of AKR1C1 gene. This process is mediated by the transcription factor NF-Y. This study explored the mechanism for the regulation