WorldWideScience

Sample records for cellular lipid metabolism

  1. Peroxisomes: a Nexus for Lipid Metabolism and Cellular Signaling

    OpenAIRE

    Lodhi, Irfan J.; Semenkovich, Clay F.

    2014-01-01

    Peroxisomes are often dismissed as the cellular hoi polloi, relegated to cleaning up reactive oxygen chemical debris discarded by other organelles. However, their functions extend far beyond hydrogen peroxide metabolism. Peroxisomes are intimately associated with lipid droplets and mitochondria, and their ability to carry out fatty acid oxidation and lipid synthesis, especially the production of ether lipids, may be critical for generating cellular signals required for normal physiology. Here...

  2. Alteration of cellular lipids and lipid metabolism markers in RTL-W1 cells exposed to model endocrine disrupters.

    Science.gov (United States)

    Dimastrogiovanni, Giorgio; Córdoba, Marlon; Navarro, Isabel; Jáuregui, Olga; Porte, Cinta

    2015-08-01

    This work investigates the suitability of the rainbow trout liver cell line (RTL-W1) as an in-vitro model to study the ability of model endocrine disrupters, namely TBT, TPT, 4-NP, BPA and DEHP, to act as metabolic disrupters by altering cellular lipids and markers of lipid metabolism. Among the tested compounds, BPA and DEHP significantly increased the intracellular accumulation of triacylglycerols (TAGs), while all the compounds -apart from TPT-, altered membrane lipids - phosphatidylcholines (PCs) and plasmalogen PCs - indicating a strong interaction of the toxicants with cell membranes and cell signaling. RTL-W1 expressed a number of genes involved in lipid metabolism that were modulated by exposure to BPA, TBT and TPT (up-regulation of FATP1 and FAS) and 4-NP and DEHP (down-regulation of FAS and LPL). Multiple and complex modes of action of these chemicals were observed in RTL-W1 cells, both in terms of expression of genes related to lipid metabolism and alteration of cellular lipids. Although further characterization is needed, this might be a useful model for the detection of chemicals leading to steatosis or other diseases associated with lipid metabolism in fish. PMID:26143618

  3. Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

    Science.gov (United States)

    We previously showed that curcumin (CUR) may increase lipid accumulation in cultured THP-1 monocytes/macrophages, but tetrahydrocurcumin (THC), an in vivo metabolite of CUR, had no such effect. In the present study, we have hypothesized that different cellular uptake and/or metabolism of CUR and THC...

  4. Regulation of lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  5. Lipid Metabolism

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  6. Lipid Chaperones and Metabolic Inflammation

    Directory of Open Access Journals (Sweden)

    Masato Furuhashi

    2011-01-01

    Full Text Available Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs, a family of lipid chaperones, as well as endoplasmic reticulum (ER stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis.

  7. 'Biomoleculas': cellular metabolism didactic software

    International Nuclear Information System (INIS)

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  8. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds......, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  9. Dysregulated lipid metabolism in cancer

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  10. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  11. Lipid metabolism in mitochondrial membranes.

    Science.gov (United States)

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  12. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores.

    Science.gov (United States)

    Bickel, Perry E; Tansey, John T; Welte, Michael A

    2009-06-01

    The PAT family of lipid droplet proteins includes 5 members in mammals: perilipin, adipose differentiation-related protein (ADRP), tail-interacting protein of 47 kDa (TIP47), S3-12, and OXPAT. Members of this family are also present in evolutionarily distant organisms, including insects, slime molds and fungi. All PAT proteins share sequence similarity and the ability to bind intracellular lipid droplets, either constitutively or in response to metabolic stimuli, such as increased lipid flux into or out of lipid droplets. Positioned at the lipid droplet surface, PAT proteins manage access of other proteins (lipases) to the lipid esters within the lipid droplet core and can interact with cellular machinery important for lipid droplet biogenesis. Genetic variations in the gene for the best-characterized of the mammalian PAT proteins, perilipin, have been associated with metabolic phenotypes, including type 2 diabetes mellitus and obesity. In this review, we discuss how the PAT proteins regulate cellular lipid metabolism both in mammals and in model organisms. PMID:19375517

  13. The role of the kidney in lipid metabolism

    DEFF Research Database (Denmark)

    Moestrup, Søren K; Nielsen, Lars Bo

    2005-01-01

    PURPOSE OF REVIEW: Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma...... proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism. RECENT FINDINGS: Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid-binding and...... regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential for the...

  14. Cellular compartmentalization of secondary metabolism

    Directory of Open Access Journals (Sweden)

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  15. Scoparone affects lipid metabolism in primary hepatocytes using lipidomics.

    Science.gov (United States)

    Zhang, Aihua; Qiu, Shi; Sun, Hui; Zhang, Tianlei; Guan, Yu; Han, Ying; Yan, Guangli; Wang, Xijun

    2016-01-01

    Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of scoparone on lipid metabolism in hepatocytes. The most striking finding was that scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics. PMID:27306123

  16. FAT SIGNALS - Lipases and Lipolysis in Lipid Metabolism and Signaling

    OpenAIRE

    Zechner, Rudolf; Zimmermann, Robert; Eichmann, Thomas O.; Kohlwein, Sepp D.; Haemmerle, Guenter; Lass, Achim; Madeo, Frank

    2012-01-01

    Lipolysis is defined as the catabolism of triacylglycerols stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. New findings that lipolytic products and intermediates participate in cellular signaling processes and that “lipolytic signaling” is particularly important in many nonadipose tissues unveil a...

  17. Metabolism of acyl-lipids in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Li-Beisson, Yonghua; Beisson, Fred; Riekhof, Wayne

    2015-05-01

    Microalgae are emerging platforms for production of a suite of compounds targeting several markets, including food, nutraceuticals, green chemicals, and biofuels. Many of these products, such as biodiesel or polyunsaturated fatty acids (PUFAs), derive from lipid metabolism. A general picture of lipid metabolism in microalgae has been deduced from well characterized pathways of fungi and land plants, but recent advances in molecular and genetic analyses of microalgae have uncovered unique features, pointing out the necessity to study lipid metabolism in microalgae themselves. In the past 10 years, in addition to its traditional role as a model for photosynthetic and flagellar motility processes, Chlamydomonas reinhardtii has emerged as a model organism to study lipid metabolism in green microalgae. Here, after summarizing data on total fatty acid composition, distribution of acyl-lipid classes, and major acyl-lipid molecular species found in C. reinhardtii, we review the current knowledge on the known or putative steps for fatty acid synthesis, glycerolipid desaturation and assembly, membrane lipid turnover, and oil remobilization. A list of characterized or putative enzymes for the major steps of acyl-lipid metabolism in C. reinhardtii is included, and subcellular localizations and phenotypes of associated mutants are discussed. Biogenesis and composition of Chlamydomonas lipid droplets and the potential importance of lipolytic processes in increasing cellular oil content are also highlighted. PMID:25660108

  18. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  19. Lipid metabolism in experimental animals

    Directory of Open Access Journals (Sweden)

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  20. Lipid transfer and metabolism across the endolysosomal-mitochondrial boundary.

    Science.gov (United States)

    Daniele, Tiziana; Schiaffino, Maria Vittoria

    2016-08-01

    Lysosomes and mitochondria occupy a central stage in the maintenance of cellular homeostasis, by playing complementary roles in nutrient sensing and energy metabolism. Specifically, these organelles function as signaling hubs that integrate environmental and endogenous stimuli with specific metabolic responses. In particular, they control various lipid biosynthetic and degradative pipelines, either directly or indirectly, by regulating major cellular metabolic pathways, and by physical and functional connections established with each other and with other organelles. Membrane contact sites allow the exchange of ions and molecules between organelles, even without membrane fusion, and are privileged routes for lipid transfer among different membrane compartments. These inter-organellar connections typically involve the endoplasmic reticulum. Direct membrane contacts have now been described also between lysosomes, autophagosomes, lipid droplets, and mitochondria. This review focuses on these recently identified membrane contact sites, and on their role in lipid biosynthesis, exchange, turnover and catabolism. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26852832

  1. The Perilipins: Major Cytosolic Lipid Droplet-Associated Proteins and Their Roles in Cellular Lipid Storage, Mobilization, and Systemic Homeostasis.

    Science.gov (United States)

    Kimmel, Alan R; Sztalryd, Carole

    2016-07-17

    The discovery by Dr. Constantine Londos of perilipin 1, the major scaffold protein at the surface of cytosolic lipid droplets in adipocytes, marked a fundamental conceptual change in the understanding of lipolytic regulation. Focus then shifted from the enzymatic activation of lipases to substrate accessibility, mediated by perilipin-dependent protein sequestration and recruitment. Consequently, the lipid droplet became recognized as a unique, metabolically active cellular organelle and its surface as the active site for novel protein-protein interactions. A new area of investigation emerged, centered on lipid droplets' biology and their role in energy homeostasis. The perilipin family is of ancient origin and has expanded to include five mammalian genes and a growing list of evolutionarily conserved members. Universally, the perilipins modulate cellular lipid storage. This review provides a summary that connects the perilipins to both cellular and whole-body homeostasis. PMID:27431369

  2. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    Science.gov (United States)

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  3. Alterations of lipid metabolism in Wilson disease

    OpenAIRE

    Stremmel Wolfgang; Eckert Nicola; Pfeiffenberger Jan; Gotthardt Daniel; Gohdes Annina; Seessle Jessica; Reuner Ulrike; Weiss Karl

    2011-01-01

    Abstract Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to dat...

  4. Assessing compartmentalized flux in lipid metabolism with isotopes.

    Science.gov (United States)

    Allen, Doug K

    2016-09-01

    Metabolism in plants takes place across multiple cell types and within distinct organelles. The distributions equate to spatial heterogeneity; though the limited means to experimentally assess metabolism frequently involve homogenizing tissues and mixing metabolites from different locations. Most current isotope investigations of metabolism therefore lack the ability to resolve spatially distinct events. Recognition of this limitation has resulted in inspired efforts to advance metabolic flux analysis and isotopic labeling techniques. Though a number of these efforts have been applied to studies in central metabolism; recent advances in instrumentation and techniques present an untapped opportunity to make similar progress in lipid metabolism where the use of stable isotopes has been more limited. These efforts will benefit from sophisticated radiolabeling reports that continue to enrich our knowledge on lipid biosynthetic pathways and provide some direction for stable isotope experimental design and extension of MFA. Evidence for this assertion is presented through the review of several elegant stable isotope studies and by taking stock of what has been learned from radioisotope investigations when spatial aspects of metabolism were considered. The studies emphasize that glycerolipid production occurs across several locations with assembly of lipids in the ER or plastid, fatty acid biosynthesis occurring in the plastid, and the generation of acetyl-CoA and glycerol-3-phosphate taking place at multiple sites. Considering metabolism in this context underscores the cellular and subcellular organization that is important to enhanced production of glycerolipids in plants. An attempt is made to unify salient features from a number of reports into a diagrammatic model of lipid metabolism and propose where stable isotope labeling experiments and further flux analysis may help address questions in the field. This article is part of a Special Issue entitled: Plant Lipid

  5. Synthetic redesign of plant lipid metabolism.

    Science.gov (United States)

    Haslam, Richard P; Sayanova, Olga; Kim, Hae Jin; Cahoon, Edgar B; Napier, Johnathan A

    2016-07-01

    Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non-native host is considered. The advantages of a particular oilseed crop, Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio-based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more (computationally) directed manipulations of metabolism. PMID:27483205

  6. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  7. High fat intake and equine lipid metabolism

    OpenAIRE

    Geelen, Suzanne Nicole Jeanne

    2002-01-01

    This thesis deals with the influence of fat feeding on lipid metabolism in horses. Highfat diets have attained considerable interest as a potential tool to improve performance.Many factors affect performance so that large numbers of horses are needed to unequivocally determine the effect of diet on performance. In practice, the execution of trials on diet in relation to performance is not possible. However, based on the reported effects of nutrition on metabolism, it should be possible to pre...

  8. Hepatic glucose and lipid metabolism.

    Science.gov (United States)

    Jones, John G

    2016-06-01

    The liver has a central role in the regulation of systemic glucose and lipid fluxes during feeding and fasting and also relies on these substrates for its own energy needs. These parallel requirements are met by coordinated control of carbohydrate and lipid fluxes into and out of the Krebs cycle, which is highly tuned to nutrient availability and heavily regulated by insulin and glucagon. During progression of type 2 diabetes, hepatic carbohydrate and lipid biosynthesis fluxes become elevated, thus contributing to hyperglycaemia and hypertriacylglycerolaemia. Over this interval there are also significant fluctuations in hepatic energy state. To date, it is not known to what extent abnormal glucose and lipid fluxes are causally linked to altered energy states. Recent evidence that the glucose-lowering effects of metformin appear to be mediated by attenuation of hepatic energy generation places an additional spotlight on the interdependence of hepatic biosynthetic and oxidative fluxes. The transition from fasting to feeding results in a significant re-direction of hepatic glucose and lipid fluxes and may also incur a temporary hepatic energy deficit. At present, it is not known to what extent these variables are additionally modified by type 2 diabetes and/or non-alcoholic fatty liver disease. Thus, there is a compelling need to measure fluxes through oxidative, gluconeogenic and lipogenic pathways and determine their relationship with hepatic energy state in both fasting and fed conditions. New magnetic resonance-based technologies allow these variables to be non-invasively studied in animal models and humans. This review summarises a presentation given at the symposium entitled 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by Hannele Yki-Järvinen, DOI: 10.1007/s00125-016-3944-1 ) and a commentary by the Session Chair, Michael

  9. Optimal flux patterns in cellular metabolic networks

    Energy Technology Data Exchange (ETDEWEB)

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  10. Editorial; Lipids in Metabolic Health and Disease

    OpenAIRE

    Glatz, Jan; De Groot, Renate; Hesselink, Matthijs; Schrauwen, Patrick

    2012-01-01

    Glatz, J. F. C., De Groot, R. H. M., Hesselink, K. C., & Schrauwen, P. (2011). Editorial; Lipids in Metabolic Health and Disease. Prostaglandines, Leukotrienes and Essential fatty Acids, 85, 195. DOI: 10.1016/j.plefa.2011.04.006

  11. The role of ER stress in lipid metabolism and lipotoxicity.

    Science.gov (United States)

    Han, Jaeseok; Kaufman, Randal J

    2016-08-01

    The endoplasmic reticulum (ER) is a cellular organelle important for regulating calcium homeostasis, lipid metabolism, protein synthesis, and posttranslational modification and trafficking. Numerous environmental, physiological, and pathological insults disturb ER homeostasis, referred to as ER stress, in which a collection of conserved intracellular signaling pathways, termed the unfolded protein response (UPR), are activated to maintain ER function for cell survival. However, excessive and/or prolonged UPR activation leads to initiation of self-destruction through apoptosis. Excessive accumulation of lipids and their intermediate products causes metabolic abnormalities and cell death, called lipotoxicity, in peripheral organs, including the pancreatic islets, liver, muscle, and heart. Because accumulating evidence links chronic ER stress and defects in UPR signaling to lipotoxicity in peripheral tissues, understanding the role of ER stress in cell physiology is a topic under intense investigation. In this review, we highlight recent findings that link ER stress and UPR signaling to the pathogenesis of peripheral organs due to lipotoxicity. PMID:27146479

  12. Stress-induced neutral lipid biosynthesis in microalgae - Molecular, cellular and physiological insights.

    Science.gov (United States)

    Zienkiewicz, Krzysztof; Du, Zhi-Yan; Ma, Wei; Vollheyde, Katharina; Benning, Christoph

    2016-09-01

    Photosynthetic microalgae have promise as biofuel feedstock. Under certain conditions, they produce substantial amounts of neutral lipids, mainly in the form of triacylglycerols (TAGs), which can be converted to fuels. Much of our current knowledge on the genetic and molecular basis of algal neutral lipid metabolism derives mainly from studies of plants, i.e. seed tissues, and to a lesser extent from direct studies of algal lipid metabolism. Thus, the knowledge of TAG synthesis and the cellular trafficking of TAG precursors in algal cells is to a large extent based on genome predictions, and most aspects of TAG metabolism have yet to be experimentally verified. The biofuel prospects of microalgae have raised the interest in mechanistic studies of algal TAG biosynthesis in recent years and resulted in an increasing number of publications on lipid metabolism in microalgae. In this review we summarize the current findings on genetic, molecular and physiological studies of TAG accumulation in microalgae. Special emphasis is on the functional analysis of key genes involved in TAG synthesis, molecular mechanisms of regulation of TAG biosynthesis, as well as on possible mechanisms of lipid droplet formation in microalgal cells. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:26883557

  13. Apolipoprotein gene involved in lipid metabolism

    Science.gov (United States)

    Rubin, Edward; Pennacchio, Len A.

    2007-07-03

    Methods and materials for studying the effects of a newly identified human gene, APOAV, and the corresponding mouse gene apoAV. The sequences of the genes are given, and transgenic animals which either contain the gene or have the endogenous gene knocked out are described. In addition, single nucleotide polymorphisms (SNPs) in the gene are described and characterized. It is demonstrated that certain SNPs are associated with diseases involving lipids and triglycerides and other metabolic diseases. These SNPs may be used alone or with SNPs from other genes to study individual risk factors. Methods for intervention in lipid diseases, including the screening of drugs to treat lipid-related or diabetic diseases are also disclosed.

  14. MicroRNA Regulation of Lipid Metabolism

    OpenAIRE

    Flowers, Elena; Froelicher, Erika Sivarajan; Aouizerat, Bradley E.

    2012-01-01

    MicroRNA are structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. Recently, there is significant interest in the application of microRNA as a blood-based biomarker of underlying physiologic conditions, and the therapeutic administration of microRNA inhibitors and mimics. The purpose of this review is to describe the current body of knowledge on microRNA regulation of genes involved in lipid metabolism, and to introduce the role of m...

  15. PEG functionalized luminescent lipid particles for cellular imaging

    Science.gov (United States)

    Rana, Suman; Barick, K. C.; Shetake, Neena G.; Verma, Gunjan; Aswal, V. K.; Panicker, Lata; Pandey, B. N.; Hassan, P. A.

    2016-08-01

    We report here the synthesis, characterization and cellular uptake of luminescent micelle-like particles with phospholipid core and non-ionic PEG based surfactant polysorbate 80 shell. The adsorption of polysorbate 80 at the interface of lipid containing microemulsion droplets and its solidification upon removal of solvent leads to anchoring of PEG chain to the lipid particles. Hydrophobic partitioning of luminescent molecules, sodium 3-hydroxynaphthalene-2-carboxylic acid to the phospholipid core offers additional functionality to these particles. Thus, the cooperative assembly of lipid, non-ionic amphiphile and organic luminescent probe leads to the formation of multifunctional biocompatible particles which are useful for simultaneous imaging and therapy.

  16. Alterations of lipid metabolism in Wilson disease

    Directory of Open Access Journals (Sweden)

    Stremmel Wolfgang

    2011-05-01

    Full Text Available Abstract Introduction Wilson disease (WD is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. Patients and Methods This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL and low density lipoprotein (LDL. Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic and treatment (D-penicillamine, trientine, zinc or combination. Results A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. Conclusion Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats, the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment.

  17. Lipid metabolism and nutrient partitioning strategies.

    Science.gov (United States)

    Morris, A M; Calsbeek, D J; Eckel, R H

    2004-10-01

    The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task. PMID:15544448

  18. Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid

    Directory of Open Access Journals (Sweden)

    Daniel Fraher

    2016-02-01

    Full Text Available The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis.

  19. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael;

    2013-01-01

    prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  20. REGULATION OF LIPID METABOLISM AND MILK LIPID CONTENT IN NORTHERN ELEPHANT SEALS

    OpenAIRE

    Fowler, Melinda Anne

    2012-01-01

    Animals that fast depend on mobilizing lipid stores to power metabolism. Northern elephant seals (Mirounga angustirostris) incorporate extended fasting into several life history stages: post weaning development, molting, breeding and lactation. The mobilization and subsequent utilization of lipid stores could have consequences for the current and future survival and reproduction. Despite the importance of lipid metabolism to elephant seals little is known about the regulation of lipid mobiliz...

  1. Label-Free Analysis of Cellular Lipid Droplet Formation by Non-Linear Microscopy

    Science.gov (United States)

    Schie, Iwan W.

    Cellular lipid droplets (LD) are cellular organelles that can be found in every cell type. Recent research indicates that cellular LD are involved in a large number of cellular metabolic functions, such as lipid metabolism, protection from lipotoxicity, protein storage and degradation, and many more. LD formation is frequently associated with adverse health effects, i.e. alcoholic and non-alcoholic fatty liver disease, diabetes type-2, as well as many cardiovascular disorders. Despite their wide presence, LDs are the least studied and most poorly understood cellular organelles. Typically, LDs are investigated using fluorescence-based techniques that require staining with exogenous fluorophores. Other techniques, e.g. biochemical assays, require the destruction of cells that prohibit the analysis of living cells. Therefore, in my thesis research I developed a novel compound fast-scanning nonlinear optical microscope equipped with the ability to also acquire Raman spectra at specific image locations. This system allows us to image label-free cellular LD formation in living cells and analyze the composition of single cellular LDs. Images can be acquired at near video-rate (˜16 frames/s). Furthermore, the system has the ability to acquire very large images of tissue of up to 7.5x15 cm2 total area by stitching together scans with dimensions of 1x1 mm2 in less than 1 minute. The system also enables the user to acquire Raman spectra from points of interest in the multiphoton images and provides chemically-specific data from sample volumes as small as 1 femtoliter. In my thesis I used this setup to determine the effects of VLDL lipolysis products on primary rat hepatocytes. By analyzing the Raman spectra and comparing the peak ratios for saturated and unsaturated fatty acid it was determined that the small cellular LD are highly saturated, while large cellular LDs contain mostly unsaturated lipids. Furthermore, I established a method to determine the specific contribution

  2. Lipid Peroxidation and Lipid Metabolism in Postmenopausal Women

    OpenAIRE

    , Banu ÖNVURAL

    1998-01-01

    The aims of this study were to determine the degree of lipid peroxidation in the sera of postmenopausal women and compare this with the lipid peroxidation of a premenopausal group, and to see if there was any correlation between lipid parameters and lipid peroxidation within the groups. We assayed the lipid profiles and malondialdehyde (MDA), a marker for lipid peroxidation, in a postmenopausal group (n=57, mean age=49.4±6.6), an age-matched male group (n=21, mean age=48.5±6.7) an...

  3. Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.

    Science.gov (United States)

    Salinas, Dino G; Reyes, Juan G; De la Fuente, Milton

    2011-09-01

    Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes. PMID:21108012

  4. Intersection of the unfolded protein response and hepatic lipid metabolism

    OpenAIRE

    Lee, Ann-Hwee; Glimcher, Laurie H.

    2009-01-01

    The liver plays a central role in whole-body lipid metabolism by governing the synthesis, oxidization, transport and excretion of lipids. The unfolded protein response (UPR) was identified as a signal transduction system that is activated by ER stress. Recent studies revealed a critical role of the UPR in hepatic lipid metabolism. The IRE1/XBP1 branch of the UPR is activated by high dietary carbohydrates and controls the expression of genes involved in fatty acid and cholesterol biosynthesis....

  5. Quantitative analysis of proteome and lipidome dynamics reveals functional regulation of global lipid metabolism

    DEFF Research Database (Denmark)

    Casanovas, Albert; Sprenger, Richard R; Tarasov, Kirill; Ruckerbauer, David E; Hannibal-Bach, Hans Kristian; Zanghellini, Jürgen; Jensen, Ole N; Ejsing, Christer S

    2015-01-01

    architecture and processes during physiological adaptations in yeast. Our results reveal that activation of cardiolipin synthesis and remodeling supports mitochondrial biogenesis in the transition from fermentative to respiratory metabolism, that down-regulation of de novo sterol synthesis machinery prompts...... of peroxisomal biogenesis, via the heterodimeric Oaf1/Pip2 transcription factor. Our work demonstrates the pivotal role of lipid metabolism in adaptive processes and provides a resource to investigate its regulation at the cellular level....

  6. Imaging vertebrate digestive function and lipid metabolism in vivo

    OpenAIRE

    Otis, Jessica P.; Farber, Steven A.

    2012-01-01

    Challenges in imaging lipid-processing events in live, intact vertebrate models have historically led to reliance on cultured cell studies, thus hampering our understanding of lipid metabolism and gastrointestinal physiology. Fluorescently-labeled molecules, such as BODIPY-labeled lipids, can reveal lipid-processing events in live zebrafish (Danio rerio) and has expanded our understanding of digestive physiology. This review will cover recent advances from the past two to three years in the u...

  7. Spastin binds to lipid droplets and affects lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Chrisovalantis Papadopoulos

    2015-04-01

    Full Text Available Mutations in SPAST, encoding spastin, are the most common cause of autosomal dominant hereditary spastic paraplegia (HSP. HSP is characterized by weakness and spasticity of the lower limbs, owing to progressive retrograde degeneration of the long corticospinal axons. Spastin is a conserved microtubule (MT-severing protein, involved in processes requiring rearrangement of the cytoskeleton in concert to membrane remodeling, such as neurite branching, axonal growth, midbody abscission, and endosome tubulation. Two isoforms of spastin are synthesized from alternative initiation codons (M1 and M87. We now show that spastin-M1 can sort from the endoplasmic reticulum (ER to pre- and mature lipid droplets (LDs. A hydrophobic motif comprised of amino acids 57 through 86 of spastin was sufficient to direct a reporter protein to LDs, while mutation of arginine 65 to glycine abolished LD targeting. Increased levels of spastin-M1 expression reduced the number but increased the size of LDs. Expression of a mutant unable to bind and sever MTs caused clustering of LDs. Consistent with these findings, ubiquitous overexpression of Dspastin in Drosophila led to bigger and less numerous LDs in the fat bodies and increased triacylglycerol levels. In contrast, Dspastin overexpression increased LD number when expressed specifically in skeletal muscles or nerves. Downregulation of Dspastin and expression of a dominant-negative variant decreased LD number in Drosophila nerves, skeletal muscle and fat bodies, and reduced triacylglycerol levels in the larvae. Moreover, we found reduced amount of fat stores in intestinal cells of worms in which the spas-1 homologue was either depleted by RNA interference or deleted. Taken together, our data uncovers an evolutionarily conserved role of spastin as a positive regulator of LD metabolism and open up the possibility that dysfunction of LDs in axons may contribute to the pathogenesis of HSP.

  8. Zebrafish Lipid Metabolism: From Mediating Early Patterning to the Metabolism of Dietary Fat and Cholesterol

    OpenAIRE

    Anderson, Jennifer L; Carten, Juliana D; Farber, Steven A.

    2011-01-01

    Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review studies that employ zebrafish to better understand lipid signaling and ...

  9. [Review: plant polyphenols modulate lipid metabolism and related molecular mechanism].

    Science.gov (United States)

    Dai, Yan-li; Zou, Yu-xiao; Liu, Fan; Li, Hong-zhi

    2015-11-01

    Lipid metabolism disorder is an important risk factor to obesity, hyperlipidemia and type 2 diabetes as well as other chronic metabolic disease. It is also a key target in preventing metabolic syndrome, chronic disease prevention. Plant polyphenol plays an important role in maintaining or improving lipid profile in a variety of ways. including regulating cholesterol absorption, inhibiting synthesis and secretion of triglyceride, and lowering plasma low density lipoprotein oxidation, etc. The purpose of this article is to review the lipid regulation effects of plant polyphenols and its related mechanisms. PMID:27071245

  10. Elucidation of lipid metabolism pathways mediated by AMPK and nuclear receptors PPARδ and LXRα in human macrophages

    OpenAIRE

    Kemmerer, Marina

    2016-01-01

    Disturbances in lipid metabolism are responsible for many chronic disorders, such as type 2 diabetes and atherosclerosis. Regulation of lipid metabolism occurs by activated transcription factors peroxisome proliferator-activated receptor δ (PPARδ) and liver X receptor α (LXRα) mediating transcription of different target genes involved in regulation of fatty acid uptake and oxidation or cellular cholesterol homeostasis. This is especially relevant for the macrophages, since pathways regulated ...

  11. Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism

    OpenAIRE

    Miyares, Rosa L.; de Rezende, Vitor B.; Farber, Steven A.

    2014-01-01

    Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a mode...

  12. Effect of phosphate on lipid metabolism in Fusarium oxysporum

    OpenAIRE

    J. S. Arneja

    2014-01-01

    The effect of different phosphate levels in the growth medium on lipid metabolism in Fusarium oxysporum, was studied. An increase in the phosphate level led on to an increase in the phosphorus content of the mycelium, as well as in that of total lipids. However, higher phosphate concentrations, had no profound effect on the total lipid percentage. Among phospholipid compounds phosphatidic acid (PA) and phosphatidyl inositol were the most susceptible while phisphatidyl choline (PC) was found t...

  13. Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism.

    Science.gov (United States)

    Abruzzese, Giselle Adriana; Heber, Maria Florencia; Ferreira, Silvana Rocio; Velez, Leandro Martin; Reynoso, Roxana; Pignataro, Omar Pedro; Motta, Alicia Beatriz

    2016-07-01

    Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis. PMID:27179108

  14. Computational model of cellular metabolic dynamics

    DEFF Research Database (Denmark)

    Li, Yanjun; Solomon, Thomas; Haus, Jacob M;

    2010-01-01

    Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively...... cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data...... type 2 diabetes....

  15. Translation Factors Specify Cellular Metabolic State

    Directory of Open Access Journals (Sweden)

    Juan Mata

    2016-08-01

    Full Text Available In this issue of Cell Reports, Shah et al. present evidence that a subcomplex of the eIF3 translation initiation factor regulates translation of mRNAs encoding components of the mitochondrial electron transport chain and glycolytic enzymes, thus linking translational control with energy metabolism.

  16. Hepatitis C Virus Life Cycle and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Costin-Ioan Popescu

    2014-12-01

    Full Text Available Hepatitis C Virus (HCV infects over 150 million people worldwide. In most cases HCV infection becomes chronic, causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. HCV affects the cholesterol homeostasis and at the molecular level, every step of the virus life cycle is intimately connected to lipid metabolism. In this review, we present an update on the lipids and apolipoproteins that are involved in the HCV infectious cycle steps: entry, replication and assembly. Moreover, the result of the assembly process is a lipoviroparticle, which represents a peculiarity of hepatitis C virion. This review illustrates an example of an intricate virus-host interaction governed by lipid metabolism.

  17. A Cellular Perspective on Brain Energy Metabolism and Functional Imaging

    KAUST Repository

    Magistretti, Pierre J.

    2015-05-01

    The energy demands of the brain are high: they account for at least 20% of the body\\'s energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and pointat a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. © 2015 Elsevier Inc.

  18. Lipid metabolism and body composition in Gclm(-/-) mice

    Energy Technology Data Exchange (ETDEWEB)

    Kendig, Eric L. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Chen, Ying [Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, CO 80045 (United States); Krishan, Mansi; Johansson, Elisabet; Schneider, Scott N. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Genter, Mary Beth; Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Shertzer, Howard G., E-mail: shertzhg@ucmail.uc.edu [Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States); Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267 (United States)

    2011-12-15

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(-/-)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(-/-) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(-/-) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(-/-) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(-/-) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(-/-) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(-/-) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(-/-) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: Black-Right-Pointing-Pointer A high fat diet does not produce body weight and fat gain in Gclm(-/-) mice. Black-Right-Pointing-Pointer A high fat diet does not induce steatosis or insulin resistance in Gclm(-/-) mice. Black-Right-Pointing-Pointer Gclm(-/-) mice have high basal metabolism and mitochondrial

  19. Hypoxia. 2. Hypoxia regulates cellular metabolism

    OpenAIRE

    Wheaton, William W.; Chandel, Navdeep S.

    2010-01-01

    Adaptation to lowering oxygen levels (hypoxia) requires coordinated downregulation of metabolic demand and supply to prevent a mismatch in ATP utilization and production that might culminate in a bioenergetic collapse. Hypoxia diminishes ATP utilization by downregulating protein translation and the activity of the Na-K-ATPase. Hypoxia diminishes ATP production in part by lowering the activity of the electron transport chain through activation of the transcription factor hypoxia-inducible fact...

  20. [Effects of essential oil on lipid peroxidation and lipid metabolism in patients with chronic bronchitis].

    Science.gov (United States)

    Siurin, S A

    1997-01-01

    Natural concentrations of some essential oils were examined for effects on the system lipid peroxidation-antioxidant defense and lipid metabolism in 150 patients with chronic bronchitis. Lowering of plasm levels of dienic conjugates and ketons, activation of catalase in red cells characteristic of antioxidant effect were observed in exposure to essential oils of rosemary, basil, fir, eucalyptus. Lavender essential oil promotes normalization of the level of total lipids, ratio of total cholesterol to its alpha-fraction. PMID:9490339

  1. Comparative genomics and functional study of lipid metabolic genes in Caenorhabditis elegans

    OpenAIRE

    Zhang, Yuru; Zou, Xiaoju; Ding, Yihong; Wang, Haizhen; Wu, Xiaoyun; Liang, Bin

    2013-01-01

    Background Animal models are indispensable to understand the lipid metabolism and lipid metabolic diseases. Over the last decade, the nematode Caenorhabditis elegans has become a popular animal model for exploring the regulation of lipid metabolism, obesity, and obese-related diseases. However, the genomic and functional conservation of lipid metabolism from C. elegans to humans remains unknown. In the present study, we systematically analyzed genes involved in lipid metabolism in the C. eleg...

  2. Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research

    OpenAIRE

    Michael V. Dodson, Gary J. Hausman, LeLuo Guan, Min Du, Theodore P. Rasmussen, Sylvia P. Poulos, Priya Mir, Werner G. Bergen, Melinda E. Fernyhough, Douglas C. McFarland, Robert P. Rhoads, Beatrice Soret, James M. Reecy, Sandra G. Velleman, Zhihua Jiang

    2010-01-01

    Meat animals are unique as experimental models for both lipid metabolism and adipocyte studies because of their direct economic value for animal production. This paper discusses the principles that regulate adipogenesis in major meat animals (beef cattle, dairy cattle, and pigs), the definition of adipose depot-specific regulation of lipid metabolism or adipogenesis, and introduces the potential value of these animals as models for metabolic research including mammary biology and the ontogeny...

  3. Lipid metabolism, adipocyte depot physiology and utilization of meat animals as experimental models for metabolic research

    OpenAIRE

    Dodson, Michael V.; Hausman, Gary J.; Guan, Leluo; Du, Min; Rasmussen, Theodore P.; Poulos, Sylvia P; Mir, Priya; Bergen, Werner G.; Fernyhough, Melinda E.; McFarland, Douglas C.; Rhoads, Robert P.; Soret Lafraya, Beatriz; Reecy, James M.; Velleman, Sandra G; Jiang, Zhihua

    2010-01-01

    Meat animals are unique as experimental models for both lipid metabolism and adipocyte studies because of their direct economic value for animal production. This paper discusses the principles that regulate adipogenesis in major meat animals (beef cattle, dairy cattle, and pigs), the definition of adipose depot-specific regulation of lipid metabolism or adipogenesis, and introduces the potential value of these animals as models for metabolic research including mammary biology and the onto...

  4. Sexual dimorphism in the effects of exercise on metabolism of lipids to support resting metabolism

    OpenAIRE

    Henderson, Gregory C.

    2014-01-01

    Exercise training is generally a healthful activity and an effective intervention for reducing the risk of numerous chronic diseases including cardiovascular disease and diabetes. This is likely both a result of prevention of weight gain over time as well as direct effects of exercise on metabolism of lipids and the other macronutrient classes. Importantly, a single bout of exercise can alter lipid metabolism and metabolic rate for hours and even into the day following exercise, so individu...

  5. Zebrafish yolk lipid processing: a tractable tool for the study of vertebrate lipid transport and metabolism

    Directory of Open Access Journals (Sweden)

    Rosa L. Miyares

    2014-07-01

    Full Text Available Dyslipidemias are a major cause of morbidity and mortality in the world, particularly in developed nations. Investigating lipid and lipoprotein metabolism in experimentally tractable animal models is a crucial step towards understanding and treating human dyslipidemias. The zebrafish, a well-established embryological model, is emerging as a notable system for studies of lipid metabolism. Here, we describe the value of the lecithotrophic, or yolk-metabolizing, stages of the zebrafish as a model for studying lipid metabolism and lipoprotein transport. We demonstrate methods to assay yolk lipid metabolism in embryonic and larval zebrafish. Injection of labeled fatty acids into the zebrafish yolk promotes efficient uptake into the circulation and rapid metabolism. Using a genetic model for abetalipoproteinemia, we show that the uptake of labeled fatty acids into the circulation is dependent on lipoprotein production. Furthermore, we examine the metabolic fate of exogenously delivered fatty acids by assaying their incorporation into complex lipids. Moreover, we demonstrate that this technique is amenable to genetic and pharmacologic studies.

  6. Lipid Profile and Leptin Levels in Patients with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    This paper should be cited as: Esmaeili R, Hassanzadeh, T . [ Lipid Profile and Leptin Levels in Patients with Metabolic Syndrome ]. mljgoums . 201 4 ; 8 ( 3 : 23 - 29 [Article in Persian] Esmaeili, R.

    2014-09-01

    Full Text Available Background and Objective: Metabolic syndrome called a cluster of several metabolic disorders is associated with increased risk of cardiovascular diseases. Genetic differences in leptin receptor gene are related with the concentration and activity of leptin in that these discrepancies can influence lipid levels. We aimed to determine the association between the leptin receptor gene polymorphism on serum lipid profile and leptin activity in metabolic syndrome patients. Material and Methods: This case-control study was conducted on 200 patients with metabolic syndrome and 200 healthy individuals. Polymerase Chain Reaction (PCR and Restriction Fragment Length Polymorphisms (RFLP were used to determine genotypic distribution and allelic frequencies of polymorphisms, respectively. The plasma leptin activity was measured by a kit in a fluorescence spectrometer, and Lipid concentration by routine biochemical and enzymatic assays. Results: Two groups had significant differences in all measured factors such as lipid profiles, fast blood sugar, waist circumference, blood pressure and leptin concentration (P< 0.05. Conclusion: Given that the two groups had significant differences in blood and body measurements, no role of K656N polymorphism was observed. Overall, Lys656Asn (K656N polymorphism of leptin receptor gene is not associated with serum lipid profile and leptin activity with metabolic syndrome.

  7. Methionine restriction on lipid metabolism and its possible mechanisms.

    Science.gov (United States)

    Zhou, Xihong; He, Liuqin; Wan, Dan; Yang, Huansheng; Yao, Kang; Wu, Guoyao; Wu, Xin; Yin, Yulong

    2016-07-01

    Methionine restriction (MR) exerts many beneficial effects, such as increasing longevity, decreasing oxidative damage and alleviating inflammatory responses. Much attention has been recently focused on the effects of MR on metabolic health, especially lipid metabolism, since the increasing incidence of obesity, insulin resistance and type 2 diabetes causes a worldwide health problem. In general, MR is considered to increase de novo lipogenesis, lipolysis and fatty acid oxidation, with a result of reduced fat accumulation. However, different responses in lipid metabolism between adipose tissue and liver are declared. Therefore, in this review, we will focus on the changes of lipid metabolism responses to dietary MR. Moreover, the comparison of alterations of fat metabolism responses to dietary MR between adipose tissue and liver, and the comparison of changes between rodents and pigs is made to illustrate the tissue- and species-specific responses. In addition, the possible mechanisms that might be engaged in the regulation of MR diet on lipid metabolism are also discussed. PMID:27156065

  8. Expression profiling and comparative sequence derived insights into lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Callow, Matthew J.; Rubin, Edward M.

    2001-12-19

    Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes involved in important processes in lipid metabolism such as sterol efflux, but the utilization of information from these studies has added to our understanding of the regulation of pathways participating in the process. Coupled with these gene expression studies, cross species comparison, searching for sequences conserved through evolution, has proven to be a powerful tool to identify important non-coding regulatory sequences as well as the discovery of novel genes relevant to lipid biology. An example of the value of this approach was the recent chance discovery of a new apolipoprotein gene (apo AV) that has dramatic effects upon triglyceride metabolism in mice and humans.

  9. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Katherine M. Aird

    2015-05-01

    Full Text Available Replication stress induced by nucleotide deficiency plays an important role in cancer initiation. Replication stress in primary cells typically activates the cellular senescence tumor-suppression mechanism. Senescence bypass correlates with development of cancer, a disease characterized by metabolic reprogramming. However, the role of metabolic reprogramming in the cellular response to replication stress has been little explored. Here, we report that ataxia telangiectasia mutated (ATM plays a central role in regulating the cellular response to replication stress by shifting cellular metabolism. ATM inactivation bypasses senescence induced by replication stress triggered by nucleotide deficiency. This was due to restoration of deoxyribonucleotide triphosphate (dNTP levels through both upregulation of the pentose phosphate pathway via increased glucose-6-phosphate dehydrogenase (G6PD activity and enhanced glucose and glutamine consumption. These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation. Our data indicate that ATM status couples replication stress and metabolic reprogramming during senescence.

  10. THE ROLE OF GROWTH HORMONE IN LIPID METABOLISM

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Dewi Ratnayanti

    2013-04-01

    Full Text Available Growth hormone (GH is one of the hormones that regulate metabolism, including lipid metabolism. GH can regulate the amount of fat in the tissue and also the level of lipid profile. Growth hormone affects the lipid in the tissue and blood by modulating the lipid metabolism, especially through the regulation of synthesis, excretion and breakdown of internal lipids. Research showed that GH could consistently lower the level of total cholesterol and LDL, whereas its effect on triglyceride and HDL level showed varying results. Growth hormone induces lypolisis by stimulating the activity of HSL and LPL and thereby influenced the triglyceride level and tissue fat storage. Cholesterol and lipoprotein levels are controlled by regulating the synthesis of cholesterol by lowering the activity of HMGCoA reductase. The excretion of cholesterol through the bile is also enhanced by stimulating the activity of enzymes C7?OH. The breakdown of VLDL and LDL are enhanced by increasing the expression of LDL receptor and ApoE as well as affecting the editing of mRNA ApoB100. Increase activity of LPL is also known to be the important factor in the HDL metabolism

  11. Protein,carbohydrate and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950255 Effects of TPN and indomethacin on stressresponse and protein metabolism after surgery.QUANZhufu(全竹富),et al.General Hosp,Nanjing Com-mand,Nanjing,210002.Med J Chin PLA 1995;20(1):24-26.The study was planned to evaluate effects of TPNand indomethacin on stress response after trauma,andprotein metabolism in patients who had received totalgastrectomy for cardiac cancer of stomach.19 caseswere divided into control,TPN,and indomethacin

  12. Perilipin-related protein regulates lipid metabolism in C. elegans

    OpenAIRE

    Chughtai, Ahmed Ali; Kaššák, Filip; Kostrouchová, Markéta; Novotný, Jan Philipp; Krause, Michael W.; Saudek, Vladimír; Kostrouch, Zdenek; Kostrouchová, Marta

    2015-01-01

    Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid drople...

  13. Interconnectivity of human cellular metabolism and disease prevalence

    International Nuclear Information System (INIS)

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease–gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery

  14. Thermoneutrality modifies the impact of hypoxia on lipid metabolism.

    Science.gov (United States)

    Jun, Jonathan C; Shin, Mi-Kyung; Yao, Qiaoling; Devera, Ronald; Fonti-Bevans, Shannon; Polotsky, Vsevolod Y

    2013-02-15

    Hypoxia has been shown to rapidly increase triglycerides in mice by decreasing plasma lipoprotein clearance. However, the usual temperature of hypoxic exposure is below thermoneutrality for mice, which may increase thermogenesis and energy requirements, resulting in higher tissue lipid uptake. We hypothesize that decreased lipid clearance and ensuing hyperlipidemia are caused by hypoxic suppression of metabolism at cold temperatures and, therefore, would not occur at thermoneutrality. Twelve-week-old, male C57BL6/J mice were exposed to 6 h of 10% O₂ at the usual temperature (22°C) or thermoneutrality (30°C). Acclimation to 22°C increased lipid uptake in the heart, lungs, and brown adipose tissue, resulting in lower plasma triglyceride and cholesterol levels. At this temperature, hypoxia attenuated lipid uptake in most tissues, thereby raising plasma triglycerides and LDL cholesterol. Thermoneutrality decreased tissue lipid uptake, and hypoxia did not cause a further reduction in lipid uptake in any organs. Consequently, hypoxia at thermoneutrality did not affect plasma triglyceride levels. Unexpectedly, plasma HDL cholesterol increased. The effect of hypoxia on white adipose tissue lipolysis was also modified by temperature. Independent of temperature, hypoxia increased heart rate and glucose and decreased activity, body temperature, and glucose sensitivity. Our study underscores the importance of ambient temperature for hypoxia research, especially in studies of lipid metabolism. PMID:23249698

  15. Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Xue-Mei Gu; Han-Chang Huang; Zhao-Feng Jiang

    2012-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder.The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau,as well as neuronal loss in specific brain regions.Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease.Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ,accumulation of which might interfere with the homeostasis of cellular metabolism.Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis.Mitochondrial dysfunction might contribute to Aβ neurotoxicity.In this review,we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

  16. The Importance of Folates for Lipid Metabolism

    Czech Academy of Sciences Publication Activity Database

    Kohlíková, E.; Petr, M.; Přistoupilová, K.; Přistoupil, T. I.; Pelclová, D.; Žák, J.; Heyrovský, Michael; Navrátil, Tomáš

    Praha: IV. interní klinika 1. LF UK Praha, 2008, s. 38-41. ISBN 978-80-254-2834-4. [Atherosklerosa 2008. Praha (CZ), 10.09.2008-12.09.2008] R&D Projects: GA ČR GA203/07/1195; GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : lipids * creatine * cholesterol * atherosclerosis Subject RIV: CF - Physical ; Theoretical Chemistry

  17. Heritability and genetics of lipid metabolism

    DEFF Research Database (Denmark)

    Fenger, Mogens

    2007-01-01

    In this article, the concept of heritability and genetic effect will be reviewed and our current knowledge of the genetics of lipid metabolism summarized. The concepts of polygenic conditions and epistasis are discussed at length, and an effort is made to put the biological processes in context...... in the search for genetic factors influencing the metabolic pathways. Particular physiological heterogeneity is addressed and procedures to handle this complex issue are suggested....

  18. JAZF1 can regulate the expression of lipid metabolic genes and inhibit lipid accumulation in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Guang-feng [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Xiao, Di; Gong, Wei-jing [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Hui-xia; Liu, Jun [Department of Geriatrics, Xiangya Hospital, Central South University, Changsha 410008, Hunan (China); Zhou, Hong-hao [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China); Liu, Zhao-qian, E-mail: liuzhaoqian63@126.com [Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha 410078, Hunan (China)

    2014-03-14

    Highlights: • JAZF1 was significantly upregulated during the differentiation of 3T3-L1 preadipocytes. • JAZF1 overexpression inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes. • JAZF1 overexpression inhibited the expression of SREBP1, ACC, and FAS. • JAZF1 overexpression upregulated the expression of HSL and ATGL. • SREBP1 and JAZF1 could regulate each other in adipocytes. - Abstract: JAZF1 is a newly identified gene with unknown functions. A recent genome-wide association study showed that JAZF1 is associated with type 2 diabetes and is highly expressed in liver and adipose tissue. Studies have demonstrated that JAZF1 is the co-repressor for nuclear orphan receptor TAK1, whereas most nuclear orphan receptor family members are involved in the regulation of lipid metabolism. Therefore, JAZF1 could be closely related to glycolipid metabolism. In this study, JAZF1 was significantly upregulated during the induced differentiation process of 3T3-L1 preadipocytes. The overexpression of JAZF1 inhibited lipid accumulation in differentiated mature 3T3-L1 adipocytes and significantly inhibited the expression of SREBPl, ACC, and FAS, which were important in lipid synthesis, while upregulating the expression of key enzyme hormone-sensitive lipase in lipoclasis. Moreover, SREBPl exhibited an inhibitory function on the expression of JAZF1. SREBP1 reversed the inhibitory action on lipid accumulation of JAZF1. SREBP1 and JAZF1 were observed to regulate each other in adipocytes. Therefore, JAZF1 could regulate the expression of particular genes related to lipid metabolism and inhibit lipid accumulation in adipocytes. This result suggests that JAZF1 may be a potential target for the treatment of diseases, such as obesity and lipid metabolism disorders.

  19. A novel alkyne cholesterol to trace cellular cholesterol metabolism and localization.

    Science.gov (United States)

    Hofmann, Kristina; Thiele, Christoph; Schött, Hans-Frieder; Gaebler, Anne; Schoene, Mario; Kiver, Yuriy; Friedrichs, Silvia; Lütjohann, Dieter; Kuerschner, Lars

    2014-03-01

    Cholesterol is an important lipid of mammalian cells and plays a fundamental role in many biological processes. Its concentration in the various cellular membranes differs and is tightly regulated. Here, we present a novel alkyne cholesterol analog suitable for tracing both cholesterol metabolism and localization. This probe can be detected by click chemistry employing various reporter azides. Alkyne cholesterol is accepted by cellular enzymes from different biological species (Brevibacterium, yeast, rat, human) and these enzymes include cholesterol oxidases, hydroxylases, and acyl transferases that generate the expected metabolites in in vitro and in vivo assays. Using fluorescence microscopy, we studied the distribution of cholesterol at subcellular resolution, detecting the lipid in the Golgi and at the plasma membrane, but also in the endoplasmic reticulum and mitochondria. In summary, alkyne cholesterol represents a versatile, sensitive, and easy-to-use tool for tracking cellular cholesterol metabolism and localization as it allows for manifold detection methods including mass spectrometry, thin-layer chromatography/fluorography, and fluorescence microscopy. PMID:24334219

  20. Regulation of lipid metabolism by angiopoietin-like proteins

    NARCIS (Netherlands)

    Dijk, Wieneke; Kersten, Sander

    2016-01-01

    PURPOSE OF REVIEW: The angiopoietin-like proteins (ANGPTLs) 3, 4 and 8 have emerged as key regulators of plasma lipid metabolism by serving as potent inhibitors of the enzyme lipoprotein lipase (LPL). In this review, we provide an integrated picture of the role of ANGPTL3, ANGPTL4 and ANGPTL8 in

  1. Lipid imbalance in the progressive neurological metabolic disorder, Farber disease

    OpenAIRE

    Ribeiro, Maria Gil Roseira; Ferreira, Natália; Alves, Mariana; Ribeiro, Isaura

    2010-01-01

    Farber disease is a neurodegenerative metabolic inherited disease caused by the deficient activity of acid ceramidase which leads to ceramide accumulation within lysosomes. Besides the structural role in biomembranes ceramide also acts as signalling molecule. The present study investigated whether intracellular trafficking of lipid molecules is blocked in diseased fibroblasts. The observation of secondary lysosomal glycosphingolipids and cholesterol storage in Farber cells rein...

  2. Dynamics of lipid metabolism under the physical activity influence

    Directory of Open Access Journals (Sweden)

    Evdokimov E.I.

    2010-07-01

    Full Text Available The results of influence of the physical loading are considered on the state of lipid exchange for practically healthy people and patients with a general metabolic syndrome. In research 38 sportsmen in age 22 - 27 years and 20 patients (women and men took part by age of 35-47лет. Influence of physical exercises was estimated on the indexes of biochemical composition of blood, anthropometry, arteriotony. The complex of physical exercises was used in common with a dietotherapy during 4 months. It is set that a complex causes regression of pathological displays. Physical activity has an unidirectional effect on lipid metabolism both in athletes and persons suffering from metabolic disorders.

  3. Microsomal lipid peroxidation as a mechanism of cellular damage. [Dissertation

    Energy Technology Data Exchange (ETDEWEB)

    Kornbrust, D.J.

    1979-01-01

    The NADPH/iron-dependent peroxidation of lipids in rat liver microsomes was found to be dependent on the presence of free ferrous ion and maintains iron in the reduced Fe/sup 2 +/ state. Chelation of iron by EDTA inhibited peroxidation. Addition of iron, after preincubation of microsomes in the absence of iron, did not enhance the rate of peroxidation suggesting that iron acts by initiating peroxidative decomposition of membrane lipids rather than by catalyzing the breakdown of pre-formed hydroperoxides. Liposomes also underwent peroxidation in the presence of ferrous iron at a rate comparable to intact microsomes and was stimulated by ascorbate. Carbon tetrachloride initiated lipid peroxidation in the absence of free metal ions. Rates of in vitro lipid peroxidation of microsomes and homogenates were found to vary widely between different tissues and species. The effects of paraquat on lipid peroxidation was also studied. (DC)

  4. Gene expression in plant lipid metabolism in Arabidopsis seedlings.

    Directory of Open Access Journals (Sweden)

    An-Shan Hsiao

    Full Text Available Events in plant lipid metabolism are important during seedling establishment. As it has not been experimentally verified whether lipid metabolism in 2- and 5-day-old Arabidopsis thaliana seedlings is diurnally-controlled, quantitative real-time PCR analysis was used to investigate the expression of target genes in acyl-lipid transfer, β-oxidation and triacylglycerol (TAG synthesis and hydrolysis in wild-type Arabidopsis WS and Col-0. In both WS and Col-0, ACYL-COA-BINDING PROTEIN3 (ACBP3, DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1 and DGAT3 showed diurnal control in 2- and 5-day-old seedlings. Also, COMATOSE (CTS was diurnally regulated in 2-day-old seedlings and LONG-CHAIN ACYL-COA SYNTHETASE6 (LACS6 in 5-day-old seedlings in both WS and Col-0. Subsequently, the effect of CIRCADIAN CLOCK ASSOCIATED1 (CCA1 and LATE ELONGATED HYPOCOTYL (LHY from the core clock system was examined using the cca1lhy mutant and CCA1-overexpressing (CCA1-OX lines versus wild-type WS and Col-0, respectively. Results revealed differential gene expression in lipid metabolism between 2- and 5-day-old mutant and wild-type WS seedlings, as well as between CCA1-OX and wild-type Col-0. Of the ACBPs, ACBP3 displayed the most significant changes between cca1lhy and WS and between CCA1-OX and Col-0, consistent with previous reports that ACBP3 is greatly affected by light/dark cycling. Evidence of oil body retention in 4- and 5-day-old seedlings of the cca1lhy mutant in comparison to WS indicated the effect of cca1lhy on storage lipid reserve mobilization. Lipid profiling revealed differences in primary lipid metabolism, namely in TAG, fatty acid methyl ester and acyl-CoA contents amongst cca1lhy, CCA1-OX, and wild-type seedlings. Taken together, this study demonstrates that lipid metabolism is subject to diurnal regulation in the early stages of seedling development in Arabidopsis.

  5. Embryonic exposures of lithium and homocysteine and folate protection affect lipid metabolism during mouse cardiogenesis and placentation.

    Science.gov (United States)

    Han, Mingda; Evsikov, Alexei V; Zhang, Lifeng; Lastra-Vicente, Rosana; Linask, Kersti K

    2016-06-01

    Embryonic exposures can increase the risk of congenital cardiac birth defects and adult disease. The present study identifies the predominant pathways modulated by an acute embryonic mouse exposure during gastrulation to lithium or homocysteine that induces cardiac defects. High dose periconceptional folate supplementation normalized development. Microarray bioinformatic analysis of gene expression demonstrated that primarily lipid metabolism is altered after the acute exposures. The lipid-related modulation demonstrated a gender bias with male embryos showing greater number of lipid-related Gene Ontology biological processes altered than in female embryos. RT-PCR analysis demonstrated significant change of the fatty acid oxidation gene Acadm with homocysteine exposure primarily in male embryos than in female. The perturbations resulting from the exposures resulted in growth-restricted placentas with disorganized cellular lipid droplet distribution indicating lipids have a critical role in cardiac-placental abnormal development. High folate supplementation protected normal heart-placental function, gene expression and lipid localization. PMID:26993217

  6. Ubiquitin Metabolism Affects Cellular Response to Volatile Anesthetics in Yeast

    OpenAIRE

    Wolfe, Darren; Reiner, Thomas; Keeley, Jessica L.; Pizzini, Mark; Keil, Ralph L.

    1999-01-01

    To investigate the mechanism of action of volatile anesthetics, we are studying mutants of the yeast Saccharomyces cerevisiae that have altered sensitivity to isoflurane, a widely used clinical anesthetic. Several lines of evidence from these studies implicate a role for ubiquitin metabolism in cellular response to volatile anesthetics: (i) mutations in the ZZZ1 gene render cells resistant to isoflurane, and the ZZZ1 gene is identical to BUL1 (binds ubiquitin ligase), which appears to be invo...

  7. The Role of Microscopy in Understanding Atherosclerotic Lysosomal Lipid Metabolism

    Science.gov (United States)

    Gray Jerome, W.; Yancey, Patricia G.

    2003-02-01

    Microscopy has played a critical role in first identifying and then defining the role of lysosomes in formation of atherosclerotic foam cells. We review the evidence implicating lysosomal lipid accumulation as a factor in the pathogenesis of atherosclerosis with reference to the role of microscopy. In addition, we explore mechanisms by which lysosomal lipid engorgement occurs. Low density lipoproteins which have become modified are the major source of lipid for foam cell formation. These altered lipoproteins are taken into the cell via receptor-mediated endocytosis and delivered to lysosomes. Under normal conditions, lipids from these lipoproteins are metabolized and do not accumulate in lysosomes. In the atherosclerotic foam cell, this normal metabolism is inhibited so that cholesterol and cholesteryl esters accumulate in lysosomes. Studies of cultured cells incubated with modified lipoproteins suggests this abnormal metabolism occurs in two steps. Initially, hydrolysis of lipoprotein cholesteryl esters occurs normally, but the resultant free cholesterol cannot exit the lysosome. Further lysosomal cholesterol accumulation inhibits hydrolysis, producing a mixture of cholesterol and cholesteryl esters within swollen lysosomes. Various lipoprotein modifications can produce this lysosomal engorgement in vitro and it remains to be seen which modifications are most important in vivo.

  8. Effect of leptin level upon lipid metabolism in climacteric women

    International Nuclear Information System (INIS)

    To observe the relationship between leptin and obesity of climacteric women with their lipid metabolism, 110 cases of climacteric women were chosen as observation group, consisting of 69 cases obese subgroup and 45 cases non-obese group, and 60 cases of normal reproduction- age women were arranged as control group. Blood levels of leptin, INS, LDL-C, TG, HDL-C, apoA1, apoB, LH, FSH, E-2, T, and P were detected and BMI was calculated. The results showed that blood levels of leptin and INS of obese subgroup were significantly higher than those of non-obese sub-group and control group(P<0.01), and that LDL-C(5.01 mmol/L), TG(2.21mmal/L) and apoB(0.89g/L) levels in obese subgroup were significantly higher than those of control group. Furthermore, an important observation was that in climacteric women group, blood leptin level was positively and significantly correlated with insulin, BMI and several atherogenic blood lipid parameters, including LDL-C, TG and apoB. Thus, a preliminary conclusion might be reached as that the high climacteric level of leptin is associated with abnormal lipid metabolism related to atherogenity, and so leptin and lipid metabolism as a whole should be paid more attention in climateric women, especially those with obesity. (authors)

  9. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences.

    Science.gov (United States)

    Vaziri, Nosratola D

    2016-07-01

    Nephrotic syndrome results in hyperlipidemia and profound alterations in lipid and lipoprotein metabolism. Serum cholesterol, triglycerides, apolipoprotein B (apoB)-containing lipoproteins (very low-density lipoprotein [VLDL], immediate-density lipoprotein [IDL], and low-density lipoprotein [LDL]), lipoprotein(a) (Lp[a]), and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are increased in nephrotic syndrome. This is accompanied by significant changes in the composition of various lipoproteins including their cholesterol-to-triglyceride, free cholesterol-to-cholesterol ester, and phospholipid-to-protein ratios. These abnormalities are mediated by changes in the expression and activities of the key proteins involved in the biosynthesis, transport, remodeling, and catabolism of lipids and lipoproteins including apoproteins A, B, C, and E; 3-hydroxy-3-methylglutaryl-coenzyme A reductase; fatty acid synthase; LDL receptor; lecithin cholesteryl ester acyltransferase; acyl coenzyme A cholesterol acyltransferase; HDL docking receptor (scavenger receptor class B, type 1 [SR-B1]); HDL endocytic receptor; lipoprotein lipase; and hepatic lipase, among others. The disorders of lipid and lipoprotein metabolism in nephrotic syndrome contribute to the development and progression of cardiovascular and kidney disease. In addition, by limiting delivery of lipid fuel to the muscles for generation of energy and to the adipose tissues for storage of energy, changes in lipid metabolism contribute to the reduction of body mass and impaired exercise capacity. This article provides an overview of the mechanisms, consequences, and treatment of lipid disorders in nephrotic syndrome. PMID:27165836

  10. Integrating cellular metabolism into a multiscale whole-body model.

    Directory of Open Access Journals (Sweden)

    Markus Krauss

    Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

  11. Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes.

    Science.gov (United States)

    D'Aquila, Theresa; Hung, Yu-Han; Carreiro, Alicia; Buhman, Kimberly K

    2016-08-01

    Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles that function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of CLDs within this process. PMID:27108063

  12. Apolipoprotein M in lipid metabolism and cardiometabolic diseases

    DEFF Research Database (Denmark)

    Borup, Anna; Christensen, Pernille Meyer; Nielsen, Lars B.;

    2015-01-01

    chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P. SUMMARY: The...... importance in regulating endothelial function is being investigated. Furthermore, both apoM and S1P have been linked to diabetes and glucose and insulin metabolism. Finally, genetic variations in the apoM gene are associated with lipid disturbances, diabetes and rheumatoid arthritis. These findings suggest...... not only diverse effects of apoM, but also the important question of whether apoM mainly acts as a S1P carrier, if apoM carries other substances with biological effects as well, or whether the apoM protein has effects on its own....

  13. Approximating the stabilization of cellular metabolism by compartmentalization.

    Science.gov (United States)

    Fürtauer, Lisa; Nägele, Thomas

    2016-06-01

    Biochemical regulation in compartmentalized metabolic networks is highly complex and non-intuitive. This is particularly true for cells of higher plants showing one of the most compartmentalized cellular structures across all kingdoms of life. The interpretation and testable hypothesis generation from experimental data on such complex systems is a challenging step in biological research and biotechnological applications. While it is known that subcellular compartments provide defined reaction spaces within a cell allowing for the tight coordination of complex biochemical reaction sequences, its role in the coordination of metabolic signals during metabolic reprogramming due to environmental fluctuations is less clear. In the present study, we numerically analysed the effects of environmental fluctuations in a subcellular metabolic network with regard to the stability of an experimentally observed steady state in the genetic model plant Arabidopsis thaliana. Applying a method for kinetic parameter normalization, several millions of probable enzyme kinetic parameter constellations were simulated and evaluated with regard to the stability information of the metabolic homeostasis. Information about the stability of the metabolic steady state was derived from real parts of eigenvalues of Jacobian matrices. Our results provide evidence for a differential stabilizing contribution of different subcellular compartments. We could identify stabilizing and destabilizing network components which we could classify according to their subcellular localization. The findings prove that a highly dynamic interplay between intracellular compartments is preliminary for an efficient stabilization of a metabolic homeostasis after environmental perturbation. Further, our results provide evidence that feedback-inhibition originating from the cytosol and plastid seem to stabilize the sucrose homeostasis more efficiently than vacuolar control. In summary, our results indicate stabilizing and

  14. Gene delivery by cationic lipid vectors : overcoming cellular barriers

    NARCIS (Netherlands)

    Zuhorn, Inge S; Engberts, Jan B F N; Hoekstra, Dirk

    2007-01-01

    Non-viral vectors such as cationic lipids are capable of delivering nucleic acids, including genes, siRNA or antisense RNA into cells, thus potentially resulting in their functional expression. These vectors are considered as an attractive alternative for virus-based delivery systems, which may suff

  15. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    Science.gov (United States)

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. PMID:20691590

  16. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    Science.gov (United States)

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID:25141153

  17. Berberine Moderates Glucose and Lipid Metabolism through Multipathway Mechanism

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    2011-01-01

    Full Text Available Berberine is known to improve glucose and lipid metabolism disorders, but the mechanism is still under investigation. In this paper, we explored the effects of berberine on the weight, glucose levels, lipid metabolism, and serum insulin of KKAy mice and investigated its possible glucose and lipid-regulating mechanism. We randomly divided KKAy mice into two groups: berberine group (treated with 250 mg/kg/d berberine and control group. Fasting blood glucose (FBG, weight, total cholesterol (TC, triglyceride (TG, high-density lipoprotein-cholesterol (HDL-c, low-density lipoprotein-cholesterol (LDL-c, and fasting serum insulin were measured in both groups. The oral glucose tolerance test (OGTT was performed. RT2 PCR array gene expression analysis was performed using skeletal muscle of KKAy mice. Our data demonstrated that berberine significantly decreased FBG, area under the curve (AUC, fasting serum insulin (FINS, homeostasis model assessment insulin resistance (HOMA-IR index, TC, and TG, compared with those of control group. RT2 profiler PCR array analysis showed that berberine upregulated the expression of glucose transporter 4 (GLUT4, mitogen-activated protein kinase 14 (MAPK14, MAPK8(c-jun N-terminal kinase, JNK, peroxisome proliferator-activated receptor α (PPARα, uncoupling protein 2 (UCP2, and hepatic nuclear factor 4α(HNF4α, whereas it downregulated the expression of PPARγ, CCAAT/enhancer-binding protein (CEBP, PPARγ coactivator 1α(PGC 1α, and resistin. These results suggest that berberine moderates glucose and lipid metabolism through a multipathway mechanism that includes AMP-activated protein kinase-(AMPK- p38 MAPK-GLUT4, JNK pathway, and PPARα pathway.

  18. Uric acid as a modulator of glucose and lipid metabolism.

    Science.gov (United States)

    Lima, William Gustavo; Martins-Santos, Maria Emília Soares; Chaves, Valéria Ernestânia

    2015-09-01

    In humans, uric acid is the final oxidation product of purine catabolism. The serum uric acid level is based on the balance between the absorption, production and excretion of purine. Uric acid is similarly produced in the liver, adipose tissue and muscle and is primarily excreted through the urinary tract. Several factors, including a high-fructose diet and the use of xenobiotics and alcohol, contribute to hyperuricaemia. Hyperuricaemia belongs to a cluster of metabolic and haemodynamic abnormalities, called metabolic syndrome, characterised by abdominal obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. Hyperuricaemia reduction in the Pound mouse or fructose-fed rats, as well as hyperuricaemia induction by uricase inhibition in rodents and studies using cell culture have suggested that uric acid plays an important role in the development of metabolic syndrome. These studies have shown that high uric acid levels regulate the oxidative stress, inflammation and enzymes associated with glucose and lipid metabolism, suggesting a mechanism for the impairment of metabolic homeostasis. Humans lacking uricase, the enzyme responsible for uric acid degradation, are susceptible to these effects. In this review, we summarise the current knowledge of the effects of uric acid on the regulation of metabolism, primarily focusing on liver, adipose tissue and skeletal muscle. PMID:26133655

  19. Construction of Global Acyl Lipid Metabolic Map by Comparative Genomics and Subcellular Localization Analysis in the Red Alga Cyanidioschyzon merolae

    Science.gov (United States)

    Mori, Natsumi; Moriyama, Takashi; Toyoshima, Masakazu; Sato, Naoki

    2016-01-01

    Pathways of lipid metabolism have been established in land plants, such as Arabidopsis thaliana, but the information on exact pathways is still under study in microalgae. In contrast with Chlamydomonas reinhardtii, which is currently studied extensively, the pathway information in red algae is still in the state in which enzymes and pathways are estimated by analogy with the knowledge in plants. Here we attempt to construct the entire acyl lipid metabolic pathways in a model red alga, Cyanidioschyzon merolae, as an initial basis for future genetic and biochemical studies, by exploiting comparative genomics and localization analysis. First, the data of whole genome clustering by Gclust were used to identify 121 acyl lipid-related enzymes. Then, the localization of 113 of these enzymes was analyzed by GFP-based techniques. We found that most of the predictions on the subcellular localization by existing tools gave erroneous results, probably because these tools had been tuned for plants or green algae. The experimental data in the present study as well as the data reported before in our laboratory will constitute a good training set for tuning these tools. The lipid metabolic map thus constructed show that the lipid metabolic pathways in the red alga are essentially similar to those in A. thaliana, except that the number of enzymes catalyzing individual reactions is quite limited. The absence of fatty acid desaturation to produce oleic and linoleic acids within the plastid, however, highlights the central importance of desaturation and acyl editing in the endoplasmic reticulum, for the synthesis of plastid lipids as well as other cellular lipids. Additionally, some notable characteristics of lipid metabolism in C. merolae were found. For example, phosphatidylcholine is synthesized by the methylation of phosphatidylethanolamine as in yeasts. It is possible that a single 3-ketoacyl-acyl carrier protein synthase is involved in the condensation reactions of fatty acid

  20. Influence of neonatal hypothyroidism on hepatic gene expression and lipid metabolism in adulthood

    DEFF Research Database (Denmark)

    Santana-Farré, Ruymán; Mirecki-Garrido, Mercedes; Bocos, Carlos;

    2012-01-01

    , and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in the expression of hepatic genes involved in lipid metabolism, including an increased transcription of PPARa and a reduced expression of genes involved in fatty acid and cholesterol uptake, cellular...... sterol efflux, triglyceride assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to the onset of hypothyroidism in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters and to T3...... replacement with an enhanced activation of malic enzyme. In summary, we provide in vivo evidence that neonatal hypothyroidism influences the hepatic transcriptional program and tissue sensitivity to hormone treatment in adulthood. This highlights the critical role that a euthyroid state during development...

  1. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids

    OpenAIRE

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D.; Li, Yuhao

    2005-01-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro.Long-term oral administration of PGF extract (500 mg kg−1) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholestero...

  2. Silibinin regulates lipid metabolism and differentiation in functional human adipocytes

    Directory of Open Access Journals (Sweden)

    Ignazio eBarbagallo

    2016-01-01

    Full Text Available Silibinin, a natural plant flavonoid, is the main active constituent found in milk thistle (Silybum marianum. It is known to have hepatoprotective, anti-neoplastic effect and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARα, Pgc-1α and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARγ, FABP4, FAS and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodelling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARα and Pgc-1α, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes.

  3. Effect of dietary protein on lipid and glucose metabolism: implications for metabolic health

    NARCIS (Netherlands)

    Rietman, A.

    2015-01-01

    Abstract Background: Diet is an important factor in the development of the Metabolic Syndrome (Mets) and type 2 Diabetes Mellitus. Accumulation of intra hepatic lipid (IHL) can result in non-alcoholic fatty liver disease (NAFLD), which is sometimes considered the he

  4. Alterations in lipid metabolism and antioxidant status in lichen planus

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    Falguni H Panchal

    2015-01-01

    Full Text Available Background: Lichen planus (LP, a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis. Aim and Objective: The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients. Materials and Methods: The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP, malondialdehyde (MDA, and catalase (CAT activity. Results: Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC, triglycerides, and low-density lipoprotein cholesterol (LDL-C along with decreased levels of high-density lipoprotein cholesterol (HDL-C in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96 was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76 was seen between CAT activity and LP duration. Conclusion: Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in

  5. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases.

    Science.gov (United States)

    Srivastava, Rai Ajit K; Pinkosky, Stephen L; Filippov, Sergey; Hanselman, Jeffrey C; Cramer, Clay T; Newton, Roger S

    2012-12-01

    The adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism at the cellular as well as whole-body level. It is activated by low energy status that triggers a switch from ATP-consuming anabolic pathways to ATP-producing catabolic pathways. AMPK is involved in a wide range of biological activities that normalizes lipid, glucose, and energy imbalances. These pathways are dysregulated in patients with metabolic syndrome (MetS), which represents a clustering of major cardiovascular risk factors including diabetes, lipid abnormalities, and energy imbalances. Clearly, there is an unmet medical need to find a molecule to treat alarming number of patients with MetS. AMPK, with multifaceted activities in various tissues, has emerged as an attractive drug target to manage lipid and glucose abnormalities and maintain energy homeostasis. A number of AMPK activators have been tested in preclinical models, but many of them have yet to reach to the clinic. This review focuses on the structure-function and role of AMPK in lipid, carbohydrate, and energy metabolism. The mode of action of AMPK activators, mechanism of anti-inflammatory activities, and preclinical and clinical findings as well as future prospects of AMPK as a drug target in treating cardio-metabolic disease are discussed. PMID:22798688

  6. LIPID METABOLISM DISORDERS IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    L. I. Tkachenko

    2015-01-01

    Full Text Available Purpose of the study. To study lipid metabolism in chronic hepatitis C and to assess its impact on the formation of insulin resistance, steatosis and progression of liver fibrosis.Materials and methods. The study included 205 patients with chronic hepatitis C (CHC. Conducts research, depending on the genotype C, viral load and body mass index (BMI of the patients.Results. CHC patients revealed a combined hyperlipoproteinemia on the background of op-pression synthesis of apolipoproteins A1 and B. Formation of hepatic steatosis was associated with HCV genotype 3 virus-induced viral load at ≥ 6 log10 IU/ml and metabolic in VL < 6 log10 IU/ml. In patients with chronic hepatitis C genotype 1, high viral load leads to inhibition of protein synthesis conveyor ApoA1 and increased synthesis of cholesterol, accompanied by abdominal obesity and the formation of insulin resistance. CHC patients with BMI < 25 kg/m2 viral load ≥ 6 log10 ME/ml was associated with dyslipidemia IV type on D. Fredriskson (1970, hyperglycemia, insulin resistance and diabetes. The advanced stage of liver fi brosis (F ≥ 3 on a scale METAVIR and non-response to treatment were associated with a decrease in HDL cholesterol below normal. With an increase in viral load > 5 log10 ME/ml signifi cantly increased the risk of lipid and carbohydrate metabolism.

  7. D/H Ratios in Lipids as a Tool to Elucidate Microbial Metabolism

    Science.gov (United States)

    Wijker, Reto S.; Sessions, Alex L.

    2016-04-01

    Large D/H fractionations have been observed in the lipids and growth water of most organisms studied today. These fractionations have generally been assumed to be constant across most biota because they originate solely from isotope effects imposed by the highly conserved lipid biosynthetic pathway. Recent data is illustrating this conclusion as incomplete. Lipids from field and laboratory samples exhibit huge variations in D/H fractionation. In environmental samples, lipids vary in δD by up to 300 ‰ and in laboratory cultures the documented variation is up to 500 ‰ within the same organism. Remarkably, the isotope fractionation appears to be correlated with the type of metabolism employed by the host organism. However, the underlying biochemical mechanisms leading to these isotopic variations are not yet fully understood. Because the largest proportion of H-bound C in fatty acids is derived directly from NADPH during biosynthesis, the original hypothesis was that large differences in the isotopic composition of NADPH, generated by different central metabolic pathways, were the primary source of D/H variation in lipids. However, recent observations indicate that this cannot be the whole story and lead us to the conclusion that additional processes must affect the isotope composition of NADPH. These processes may include the isotopic exchange of NADPH with water as well as fractionation of NADPH by transhydrogenases, interconverting NADH to NADPH by exhibiting large isotope effects. In this project, our objective is to ascertain whether D/H fractionation and these biochemical processes are correlated. We investigate correlations between cellular NADPH/NADP+ as well as NADH/NAD+ pool sizes and the D/H fractionation in a set of different microorganisms and will present the trends here. Our results will contribute to a more comprehensive understanding of the basic biological regulations over D/H fractionation and potentially enables their use as tracers and

  8. Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting

    OpenAIRE

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional...

  9. Dynamics of lipid metabolism under the physical activity influence

    OpenAIRE

    Evdokimov E.I.; Elnikova M.V.

    2010-01-01

    The results of influence of the physical loading are considered on the state of lipid exchange for practically healthy people and patients with a general metabolic syndrome. In research 38 sportsmen in age 22 - 27 years and 20 patients (women and men) took part by age of 35-47лет. Influence of physical exercises was estimated on the indexes of biochemical composition of blood, anthropometry, arteriotony. The complex of physical exercises was used in common with a dietotherapy during 4 months....

  10. Regulatory mechanisms underlying oil palm fruit mesocarp maturation, ripening, and functional specialization in lipid and carotenoid metabolism

    OpenAIRE

    Tranbarger, Timothy; Dussert, Stéphane; Joët, Thierry; Argout, X.; Summo, M.; Champion, Antony; Cros, D.; Omore, A.; Nouy, B.; Morcillo, Fabienne

    2011-01-01

    International audience Fruit provide essential nutrients and vitamins for the human diet. Not only is the lipid-rich fleshy mesocarp tissue of the oil palm (Elaeis guineensis) fruit the main source of edible oil for the world, but it is also the richest dietary source of provitamin A. This study examines the transcriptional basis of these two outstanding metabolic characters in the oil palm mesocarp. Morphological, cellular, biochemical, and hormonal features defined key phases of mesocarp...

  11. Gemfibrozil disrupts the metabolism of circulating lipids in bobwhite quails.

    Science.gov (United States)

    Bussière-Côté, Sophie; Omlin, Teye; de Càssia Pinheiro, Eliana; Weber, Jean-Michel

    2016-01-01

    The circulating lipids of birds play essential roles for egg production and as an energy source for flight and thermogenesis. How lipid-lowering pharmaceuticals geared to prevent heart disease in humans and that are routinely released in the environment affect their metabolism is unknown. This study assesses the impact of the popular drug gemfibrozil (GEM) on the plasma phospholipids (PL), neutral lipids (NL), and nonesterified fatty acids (NEFA) of bobwhite quails (Colinus virginianus). Results show that bird lipoproteins are rapidly altered by GEM, even at environmentally-relevant doses. After 4 days of exposure, pharmacological amounts cause an 83% increase in circulating PL levels, a major decrease in average lipoprotein size measured as a 56% drop in the NL/PL ratio, and important changes in the fatty acid composition of PL and NEFA (increases in fatty acid unsaturation). The levels of PL carrying all individual fatty acids except arachidonate are strongly stimulated. The large decrease in bird lipoprotein size may reflect the effects seen in humans: lowering of LDL that can cause atherosclerosis and stimulation of HDL that promote cholesterol disposal. Lower (environmental) doses of GEM cause a reduction of %palmitate in all the plasma lipid fractions of quails, but particularly in the core triacylglycerol of lipoproteins (NL). No changes in mRNA levels of bird peroxisome proliferator-activated receptor (PPAR) could be demonstrated. The disrupting effects of GEM on circulating lipids reported here suggest that the pervasive presence of this drug in the environment could jeopardize reproduction and migratory behaviours in wild birds. PMID:26432161

  12. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  13. Modelling chronotaxicity of cellular energy metabolism to facilitate the identification of altered metabolic states

    Science.gov (United States)

    Lancaster, Gemma; Suprunenko, Yevhen F.; Jenkins, Kirsten; Stefanovska, Aneta

    2016-01-01

    Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states. PMID:27483987

  14. Untargeted Metabolomics Reveals Predominant Alterations in Lipid Metabolism Following Light Exposure in Broccoli Sprouts

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    Mariateresa Maldini

    2015-06-01

    Full Text Available The consumption of vegetables belonging to the family Brassicaceae (e.g., broccoli and cauliflower is linked to a reduced incidence of cancer and cardiovascular diseases. The molecular composition of such plants is strongly affected by growing conditions. Here we developed an unbiased metabolomics approach to investigate the effect of light and dark exposure on the metabolome of broccoli sprouts and we applied such an approach to provide a bird’s-eye view of the overall metabolic response after light exposure. Broccoli seeds were germinated and grown hydroponically for five days in total darkness or with a light/dark photoperiod (16 h light/8 h dark cycle. We used an ultra-performance liquid-chromatography system coupled to an ion-mobility, time-of-flight mass spectrometer to profile the large array of metabolites present in the sprouts. Differences at the metabolite level between groups were analyzed using multivariate statistical analyses, including principal component analysis and correlation analysis. Altered metabolites were identified by searching publicly available and in-house databases. Metabolite pathway analyses were used to support the identification of subtle but significant changes among groups of related metabolites that may have gone unnoticed with conventional approaches. Besides the chlorophyll pathway, light exposure activated the biosynthesis and metabolism of sterol lipids, prenol lipids, and polyunsaturated lipids, which are essential for the photosynthetic machinery. Our results also revealed that light exposure increased the levels of polyketides, including flavonoids, and oxylipins, which play essential roles in the plant’s developmental processes and defense mechanism against herbivores. This study highlights the significant contribution of light exposure to the ultimate metabolic phenotype, which might affect the cellular physiology and nutritional value of broccoli sprouts. Furthermore, this study highlights the

  15. Argininosuccinate synthetase regulates hepatic AMPK linking protein catabolism and ureagenesis to hepatic lipid metabolism.

    Science.gov (United States)

    Madiraju, Anila K; Alves, Tiago; Zhao, Xiaojian; Cline, Gary W; Zhang, Dongyan; Bhanot, Sanjay; Samuel, Varman T; Kibbey, Richard G; Shulman, Gerald I

    2016-06-14

    A key sensor of cellular energy status, AMP-activated protein kinase (AMPK), interacts allosterically with AMP to maintain an active state. When active, AMPK triggers a metabolic switch, decreasing the activity of anabolic pathways and enhancing catabolic processes such as lipid oxidation to restore the energy balance. Unlike oxidative tissues, in which AMP is generated from adenylate kinase during states of high energy demand, the ornithine cycle enzyme argininosuccinate synthetase (ASS) is a principle site of AMP generation in the liver. Here we show that ASS regulates hepatic AMPK, revealing a central role for ureagenesis flux in the regulation of metabolism via AMPK. Treatment of primary rat hepatocytes with amino acids increased gluconeogenesis and ureagenesis and, despite nutrient excess, induced both AMPK and acetyl-CoA carboxylase (ACC) phosphorylation. Antisense oligonucleotide knockdown of hepatic ASS1 expression in vivo decreased liver AMPK activation, phosphorylation of ACC, and plasma β-hydroxybutyrate concentrations. Taken together these studies demonstrate that increased amino acid flux can activate AMPK through increased AMP generated by ASS, thus providing a novel link between protein catabolism, ureagenesis, and hepatic lipid metabolism. PMID:27247419

  16. Genome-scale metabolic modeling and in silico analysis of lipid accumulating yeast Candida tropicalis for dicarboxylic acid production.

    Science.gov (United States)

    Mishra, Pranjul; Park, Gyu-Yeon; Lakshmanan, Meiyappan; Lee, Hee-Seok; Lee, Hongweon; Chang, Matthew Wook; Ching, Chi Bun; Ahn, Jungoh; Lee, Dong-Yup

    2016-09-01

    Recently, the bio-production of α,ω-dicarboxylic acids (DCAs) has gained significant attention, which potentially leads to the replacement of the conventional petroleum-based products. In this regard, the lipid accumulating yeast Candida tropicalis, has been recognized as a promising microbial host for DCA biosynthesis: it possess the unique ω-oxidation pathway where the terminal carbon of α-fatty acids is oxidized to form DCAs with varying chain lengths. However, despite such industrial importance, its cellular physiology and lipid accumulation capability remain largely uncharacterized. Thus, it is imperative to better understand the metabolic behavior of this lipogenic yeast, which could be achieved by a systems biological approach. To this end, herein, we reconstructed the genome-scale metabolic model of C. tropicalis, iCT646, accounting for 646 unique genes, 945 metabolic reactions, and 712 metabolites. Initially, the comparative network analysis of iCT646 with other yeasts revealed several distinctive metabolic reactions, mainly within the amino acid and lipid metabolism including the ω-oxidation pathway. Constraints-based flux analysis was, then, employed to predict the in silico growth rates of C. tropicalis which are highly consistent with the cellular phenotype observed in glucose and xylose minimal media chemostat cultures. Subsequently, the lipid accumulation capability of C. tropicalis was explored in comparison with Saccharomyces cerevisiae, indicating that the formation of "citrate pyruvate cycle" is essential to the lipid accumulation in oleaginous yeasts. The in silico flux analysis also highlighted the enhanced ability of pentose phosphate pathway as NADPH source rather than malic enzyme during lipogenesis. Finally, iCT646 was successfully utilized to highlight the key directions of C. tropicalis strain design for the whole cell biotransformation application to produce long-chain DCAs from alkanes. Biotechnol. Bioeng. 2016;113: 1993-2004.

  17. An ER Protein Functionally Couples Neutral Lipid Metabolism on Lipid Droplets to Membrane Lipid Synthesis in the ER

    Directory of Open Access Journals (Sweden)

    Daniel F. Markgraf

    2014-01-01

    Full Text Available Eukaryotic cells store neutral lipids such as triacylglycerol (TAG in lipid droplets (LDs. Here, we have addressed how LDs are functionally linked to the endoplasmic reticulum (ER. We show that, in S. cerevisiae, LD growth is sustained by LD-localized enzymes. When LDs grow in early stationary phase, the diacylglycerol acyl-transferase Dga1p moves from the ER to LDs and is responsible for all TAG synthesis from diacylglycerol (DAG. During LD breakdown in early exponential phase, an ER membrane protein (Ice2p facilitates TAG utilization for membrane-lipid synthesis. Ice2p has a cytosolic domain with affinity for LDs and is required for the efficient utilization of LD-derived DAG in the ER. Ice2p breaks a futile cycle on LDs between TAG degradation and synthesis, promoting the rapid relocalization of Dga1p to the ER. Our results show that Ice2p functionally links LDs with the ER and explain how cells switch neutral lipid metabolism from storage to consumption.

  18. Caveolin-1 Is Necessary for Hepatic Oxidative Lipid Metabolism: Evidence for Crosstalk between Caveolin-1 and Bile Acid Signaling

    Directory of Open Access Journals (Sweden)

    Manuel A. Fernández-Rojo

    2013-07-01

    Full Text Available Caveolae and caveolin-1 (CAV1 have been linked to several cellular functions. However, a model explaining their roles in mammalian tissues in vivo is lacking. Unbiased expression profiling in several tissues and cell types identified lipid metabolism as the main target affected by CAV1 deficiency. CAV1−/− mice exhibited impaired hepatic peroxisome proliferator-activated receptor α (PPARα-dependent oxidative fatty acid metabolism and ketogenesis. Similar results were recapitulated in CAV1-deficient AML12 hepatocytes, suggesting at least a partial cell-autonomous role of hepatocyte CAV1 in metabolic adaptation to fasting. Finally, our experiments suggest that the hepatic phenotypes observed in CAV1−/− mice involve impaired PPARα ligand signaling and attenuated bile acid and FXRα signaling. These results demonstrate the significance of CAV1 in (1 hepatic lipid homeostasis and (2 nuclear hormone receptor (PPARα, FXRα, and SHP and bile acid signaling.

  19. Triclosan (TCS) exposure impairs lipid metabolism in zebrafish embryos.

    Science.gov (United States)

    Ho, Jeff C H; Hsiao, C D; Kawakami, K; Tse, William K F

    2016-04-01

    Triclosan (TCS) is an active antimicrobial ingredient used in many household products, such as skin creams and toothpaste. It is produced in high volumes, and humans are directly exposed to it and dispose it on a daily basis. TCS has been found to contaminate water worldwide. This study aimed to understand the potential developmental and metabolic abnormalities caused by TCS exposure by using zebrafish as the experimental model. Four developmental stages (70-85% epiboly, 10-12 somite, prim-5, and 5dpf) were selected to perform in situ hybridization staining to investigate the effects of TCS on dorsal ventral patterning, segmentation, brain development, and organ formation. Results showed, in terms of developmental toxicology, that neither phenotypic nor molecular changes were found after 5 days of 250μg/L TCS exposure. However, such dosage of TCS exposure resulted in lipid droplet accumulation in the yolk sac, which might due to the deregulated mRNA expression level of beta-oxidation transcripts. This study showed that 250μg/L TCS exposure does not affect normal embryogenesis or organogenesis; however, there are concerns regarding possible impairment of lipid metabolism. PMID:26828895

  20. Lou/C obesity-resistant rat exhibits hyperactivity, hypermetabolism, alterations in white adipose tissue cellularity, and lipid tissue profiles.

    Science.gov (United States)

    Soulage, Christophe; Zarrouki, Bader; Soares, Anisio Francesco; Lagarde, Michel; Geloen, Alain

    2008-02-01

    Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness. PMID:18006635

  1. LIPID RATIOS: AS A PREDICTOR OF METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    Pushpa

    2015-12-01

    Full Text Available Metabolic Syndrome (MetS is a group of disorders characterized by obesity, hypertension, glucose intolerance and dyslipidemia. This study was undertaken to determine whether lipid ratios calculated by routinely measured lipid profile can be used as predictor of MetS and which among them could be used as better predictor. MATERIALS AND METHODS Data consisting of anthropometric measurements, blood pressure, laboratory parameters like fasting blood sugar, Total Cholesterol (TC, Triglycerides (TG, High Density Lipoprotein-C (HDL-C and Low Density Lipoprotein-C (LDL-C of 460 subjects was obtained by record of Community Outreach Programme conducted at Holalu village; 440 subjects with complete data were included in the study. MetS was diagnosed based on ATP III criteria. Various lipid ratios like TC/HDL-C, TG/HDL-C, Non-HDL-C/HDL-C and LDL-C/HDL-C were calculated. Results obtained were statistically analyzed using SPSS software. RESULTS Among 440 study subjects, 215 were males and 225 females with mean age of 54.37±12.68 years. 111 subjects (80 females and 31 males were diagnosed as MetS based on ATP III criteria. As the number of components of MetS increased the mean values of lipid ratios increased in both males and females. Among lipid ratios analyzed by ROC curve, TG/HDL-C was best able to discriminate individuals with MetS; the Area Under Curve (AUC being 0.717 in males and 0.760 in females. AUC of TC/HDL-C was 0.579 in males and 0.734 in females, LDL-C/HDL-C was 0.688 in females and 0.504 in males. AUC for non-HDL-C/HDL-C to identify individuals with MetS was 0.577 in males and 0.732 in females. CONCLUSION TG/HDL-C is a better indicator of the risk of MetS compared to various lipid ratios and can be used to predict the risk of MetS.

  2. Glucose regulates lipid metabolism in fasting king penguins.

    Science.gov (United States)

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production. PMID:12738609

  3. C. elegans Metabolic Gene Regulatory Networks Govern the Cellular Economy

    Science.gov (United States)

    Watson, Emma; Walhout, Albertha J.M.

    2014-01-01

    Diet greatly impacts metabolism in health and disease. In response to the presence or absence of specific nutrients, metabolic gene regulatory networks sense the metabolic state of the cell and regulate metabolic flux accordingly, for instance by the transcriptional control of metabolic enzymes. Here we discuss recent insights regarding metazoan metabolic regulatory networks using the nematode Caenorhabditis elegans as a model, including the modular organization of metabolic gene regulatory networks, the prominent impact of diet on the transcriptome and metabolome, specialized roles of nuclear hormone receptors in responding to dietary conditions, regulation of metabolic genes and metabolic regulators by microRNAs, and feedback between metabolic genes and their regulators. PMID:24731597

  4. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis.

    Science.gov (United States)

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Murphy, Therese M; Heritage, Mandy L; Subramaniam, V Nathan; Clouston, Andrew D; Anderson, Gregory J; Fletcher, Linda M

    2011-11-01

    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis. Here, we investigated the potential contribution of HFE mutations to hepatic lipid metabolism and its role in the pathogenesis of nonalcoholic fatty liver disease. Wild-type (WT) and Hfe knockout mice (Hfe(-/-)) were fed either standard chow, a monounsaturated low fat, or a high-fat, high-carbohydrate diet (HFD) and assessed for liver injury, body iron status, and markers of lipid metabolism. Despite hepatic iron concentrations and body weights similar to WT controls, Hfe(-/-) mice fed the HFD developed severe hypoxia-related steatohepatitis, Tnf-α activation, and mitochondrial respiratory complex and antioxidant dysfunction with early fibrogenesis. These features were associated with an upregulation in the expression of genes involved in intracellular lipid synthesis and trafficking, while transcripts for mitochondrial fatty acid β-oxidation and adiponectin signaling-related genes were significantly attenuated. In contrast, HFD-fed WT mice developed bland steatosis only, with no inflammation or fibrosis and no upregulation of lipogenesis-related genes. A HFD led to reduced hepatic iron in Hfe(-/-) mice compared with chow-fed mice, despite higher serum iron, decreased hepcidin expression, and increased duodenal ferroportin mRNA. In conclusion, our results demonstrate that Hfe(-/-) mice show defective hepatic-intestinal iron and lipid signaling, which predispose them toward diet-induced hepatic lipotoxicity, accompanied by an accelerated progression of injury to fibrosis. PMID:21817060

  5. Identifying lipid metabolism genes in pig liver after clenbuterol administration.

    Science.gov (United States)

    Liu, Qiuyue; Zhang, Jin; Guo, Wei; Zhao, Yiqiang; Hu, Xiaoxiang; Li, Ning

    2012-01-01

    Clenbuterol is a repartition agent (beta 2-adrenoceptor agonist) that can decrease fat deposition and increase skeletal muscle growth at manageable dose. To better understand the molecular mechanism of Clenbuterol's action, GeneChips and real-time PCR were used to compare the gene expression profiles of liver tissue in pigs with/without administration of Clenbuterol. Metabolism effects and the global gene expression profiles of liver tissue from Clenbuterol-treated and untreated pigs were conducted. Function enrichment tests showed that the differentially expressed genes are enriched in glycoprotein protein, plasma membrane, fatty acid and amino acid metabolic process, and cell differentiation and signal transduction groups. Pathway mining analysis revealed that physiological pathways such as MAPK, cell adhesion molecules, and the insulin signaling pathway, were remarkably regulated when Clenbuterol was administered. Gene prioritization algorithm was used to associate a number of important differentially expressed genes with lipid metabolism in response to Clenbuterol. Genes identified as differentially expressed in this study will be candidates for further investigation of the molecular mechanisms involved in Clenbuterol's effects on adipose and skeletal muscle tissue. PMID:22652664

  6. Cellular uptake and processing of surfactant lipids and apoprotein SP-A by rat lung

    International Nuclear Information System (INIS)

    The intracellular pathways and the kinetics of metabolism of surfactant apoprotein and lipid, which may be recycled from the alveolar space, are largely unknown. We used a lipid-apoprotein complex made from liposomes of pure lipids in a ratio found in mammalian pulmonary surfactant plus surfactant apoprotein (SP-A, Mr = 26,000-36,000) to test some possible relationships in the recycling of these major surfactant components between intrapulmonary compartments. After intratracheal instillation of 80 microliters of an apoprotein-liposome mixture with separate radiolabels in the lipid and the apoprotein, rats were killed at times from 8 min to 4 h later. The lungs were lavaged with saline, and subcellular fractions were isolated on discontinuous sucrose density gradients. Both the [14C]lipid radiolabel and the 125I-apoprotein radiolabel demonstrated a time-dependent increase in radioactivity recovered in a lamellar body-enriched fraction. Uptake of the radiolabels into other subcellular fractions did not exhibit a clear-cut time dependence; more of the protein than the lipid radiolabel was found in the Golgi-rich and microsomal fractions. We conclude that both the lipid and apoprotein portions of lung surfactant are taken up by lung cells and are incorporated into secretory granules of the cells

  7. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    Science.gov (United States)

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

  8. 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. PMID:20077421

  9. Mapping Condition-Dependent Regulation of Lipid Metabolism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Jewett, Michael Christopher; Workman, Christopher; Nookaew, Intawat; Pizarro, Francisco A; Agosin, Eduardo; Hellgren, Lars; Nielsen, Jens

    2013-01-01

    levels, and lipid levels are currently lacking. Here, we map condition-dependent regulation controlling lipid metabolism in Saccharomyces cerevisiae by measuring 5636 mRNAs, 50 metabolites, 97 lipids, and 57 13C-reaction fluxes in yeast using a three-factor full-factorial design. Correlation analysis...

  10. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    Energy Technology Data Exchange (ETDEWEB)

    Kent D. Chapman

    2009-02-06

    The Gordon Research Conference on 'Plant Lipids: Structure, Metabolism and Function' has been instituted to accelerate research productivity in the field of plant lipids. This conference will facilitate wide dissemination of research breakthroughs, support recruitment of young scientists to the field of plant lipid metabolism and encourage broad participation of the plant lipid community in guiding future directions for research in plant lipids. This conference will build upon the strengths of the successful, previous biannual meetings of the National Plant Lipid Cooperative (www.plantlipids.org) that began in 1993, but will reflect a broader scope of topics to include the biochemistry, cell biology, metabolic regulation, and signaling functions of plant acyl lipids. Most importantly, this conference also will serve as a physical focal point for the interaction of the plant lipid research community. Applications to attend this conference will be open to all researchers interested in plant lipids and will provide a venue for the presentation of the latest research results, networking opportunities for young scientists, and a forum for the development and exchange of useful lipid resources and new ideas. By bringing together senior- and junior-level scientists involved in plant lipid metabolism, a broad range of insights will be shared and the community of plant lipid researchers will function more as a network of vested partners. This is important for the vitality of the research community and for the perceived value that will encourage conference attendance into the future.

  11. Effect of fatty Amazon fish consumption on lipid metabolism

    Directory of Open Access Journals (Sweden)

    Francisca das Chagas do Amaral Souza

    2014-01-01

    Full Text Available OBJECTIVE: The present study aimed to evaluate the effect of feeding diets enriched with fatty fish from the Amazon basin on lipid metabolism. METHODS: Male Wistar rats were divided into four groups: control group treated with commercial chow; Mapará group was fed diet enriched with Hypophthalmus edentatus; Matrinxã group was fed diet enriched with Brycon spp.; and, Tambaqui group was fed diet enriched with Colossoma macropomum. Rats with approximately 240g±0.60 of body weight were fed ad libitum for 30 days, and then were sacrificed for collection of whole blood and tissues. RESULTS: The groups treated with enriched diets showed a significant reduction in body mass and lipogenesis in the epididymal and retroperitoneal adipose tissues and carcass when compared with the control group. However, lipogenesis in the liver showed an increase in Matrinxã group compared with the others groups. The levels of serum triglycerides in the treated groups with Amazonian fish were significantly lower than those of the control group. Moreover, total cholesterol concentration only decreased in the group Matrinxã. High Density Lipoprotein cholesterol levels increased significantly in the Mapará and Tambaqui compared with control group and Matrinxã group. The insulin and leptin levels increased significantly in all treatment groups. CONCLUSION: This study demonstrated that diets enriched with fatty fish from the Amazon basin changed the lipid metabolism by reducing serum triglycerides and increasing high density lipoprotein-cholesterol in rats fed with diets enriched with Mapará, Matrinxã, and Tambaqui.

  12. Features of lipid metabolism disturbances in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    A E Sizikov

    2009-01-01

    Full Text Available Objective. To characterize specters of common and modified lipoproteins (LP in serum of pts with rheumatoid arthritis (RA according to age and sex and compare with healthy donors (with normal lipid level. Material and methods. 103 pts with RA (88 female and 15 male aged 21 to 69 years were included. Specters of common and modified LP in serum and plasma were evaluated with small-angle x-ray scattering. Results. Low level of intermediate density lipoproteins (IDLP subfractions and very low density lipoproteins (VLDLP as well as high level of low density lipoproteins (LDLP30 was revealed in pts with RA. Mean level of LP modification was about 60%. High density lipoproteins (HDLP subfraction was least and IDLP subfraction – most susceptible to modification. LP modification level increased due to LDLP and VLDLP fractions. This level had a tendency to increase with age because of elevation of atherogenic LP part. Mean values of common LP did not differ between sex and age groups of pts with RA. Unexpectedly low (in comparison with normal lipid content level of LP modification of the whole fraction of HDLP was the feature of modified LP specter in pts with RA. Conclusion. Level of common and modified LP in blood plasma and serum of RA pts is connected with general state of lipid metabolism and immune defense factors balance. Low level of VLDLP cholesterol and high level of LDLP cholesterol as well as high degree of LP of these fractions modification may be probably considered as markers of RA activity.

  13. Changes in lipid metabolism in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Katalin Jármay; Gizella Karácsony; András Nagy; Zsuzsa Schaff

    2005-01-01

    AIM: To investigate the relationship between certain biochemical parameters of lipid metabolism in the serum and steatosis in the liver.METHODS: The grade of steatosis (0-3) and histological activity index (HAI, 0-18) in liver biopsy specimens were correlated with serum alanine aminotransferase (ALT), total cholesterol and triglyceride levels in 142 patients with chronic hepatitis C (CH-C), and 28 patients with non-alcoholic fatty liver disease (NAFLD) without hepatitis C virus (HCV) infection. The serum parameters were further correlated with 1 797 age and sex matched control patients without any liver diseases.RESULTS: Steatosis was detected in 90 out of 142 specimens (63%) with CH-C. The ALT levels correlated with the grade of steatosis, both in patients with CH-C and NAFLD (P<0.01). Inserting the score values of steatosis as part of the HAI, correlation with the ALT level (P<0.00001) was found. The triglyceride and cholesterol levels were significantly lower in patients with CH-C (with and without steatosis), compared to the NAFLD group and to the virus-free control groups.CONCLUSION: Our study confirms the importance of liver steatosis in CH-C which correlates with lower lipid levels in the sera. Inclusion of the score of steatosis into HAI, in case of CH-C might reflect the alterations in the liver tissue more precisely, while correlating with the ALT enzyme elevation.

  14. Environmentally Relevant Dose of Bisphenol A Does Not Affect Lipid Metabolism and Has No Synergetic or Antagonistic Effects on Genistein’s Beneficial Roles on Lipid Metabolism

    Science.gov (United States)

    Fan, Ying; Li, Hongyu; Zhao, Nana; Yang, Huiqin; Ye, Xiaolei; He, Dongliang; Yang, Hui; Jin, Xin; Tian, Chong; Ying, Chenjiang

    2016-01-01

    Both bisphenol A (BPA, an endocrine disrupting chemicals) and genistein (a phytoestrogen mainly derived from leguminosae) are able to bind to estrogen receptors, but they are considered to have different effects on metabolic syndrome, surprisingly. We here investigate the effects of an environmentally relevant dose of BPA alone and the combined effects with genistein on lipid metabolism in rats. Eight groups of adult male Wistar rats, fed with either standard chow diet or high-fat diet, were treated with BPA (50μg/kg/day), genistein (10mg/kg/day), and BPA plus genistein for 35 weeks, respectively. Metabolic parameters in serum and liver were determined; the hematoxylin/eosin and oil Red O staining were used to observe liver histologically; gene expressions related to hepatic lipid metabolism were analyzed by Real-time PCR; protein expressions of PPARγ, PPARα and LC3 in liver were analyzed by western blotting. No difference of body weight gain, total energy intake, liver weight/body weight or body fat percentage in both STD- and HFD-fed sub-groups was observed after treatment with BPA, genistein, or BPA plus genistein (P>0.05). Genistein alleviated lipid metabolism disorder and decreased the mRNA and protein expression of PPARγ (P0.05) or combined with genistein. Our findings suggest that long-term environmentally relevant dose of BPA did not affect lipid metabolism, and had no synergetic or antagonistic roles on genistein’s beneficial function on hepatic lipid metabolism. PMID:27171397

  15. The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions

    OpenAIRE

    Udenigwe, Chibuike C.; Kirsti Rouvinen-Watt

    2015-01-01

    Animal and human clinical studies have demonstrated the ability of dietary food proteins to modulate endogenous lipid levels during abnormal lipid metabolism (dyslipidemia). Considering the susceptibility of proteins to gastric proteolytic activities, the hypolipidemic functions of proteins are possibly due, in part, to their peptide fragments. Food-derived peptides may directly modulate abnormal lipid metabolism in cell cultures and animal models of dyslipidemia. The peptides are thought to...

  16. Obesity-Related Chronic Kidney Disease—The Role of Lipid Metabolism

    OpenAIRE

    Peter Mount; Matthew Davies; Suet-Wan Choy; Natasha Cook; David Power

    2015-01-01

    Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of f...

  17. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

    OpenAIRE

    María López-Malo; Estéfani García-Ríos; Rosana Chiva; José Manuel Guillamon

    2014-01-01

    Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 – 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identi...

  18. Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis

    Directory of Open Access Journals (Sweden)

    Sang Hoon Lee

    2015-01-01

    Full Text Available Background. Despite extensive research and an improved standard of care, sepsis remains a disorder with a high mortality rate. Sepsis is accompanied by severe metabolic alterations. Methods. We evaluated 117 patients with sepsis (severe sepsis [n=19] and septic shock [n=98] who were admitted to the intensive care unit. Serum cholesterol, triglyceride (TG, high-density lipoprotein (HDL, low-density lipoprotein (LDL, free fatty acid (FFA, and apolipoprotein (Apo A-I levels were measured on days 0, 1, 3, and 7. Results. Nonsurvivors had low levels of cholesterol, TG, HDL, LDL, and Apo A-I on days 0, 1, 3, and 7. In a linear mixed model analysis, the variations in TG, LDL, FFA, and Apo A-I levels over time differed significantly between the groups (p=0.043, p=0.020, p=0.005, and p=0.015, resp.. According to multivariate analysis, TG levels and SOFA scores were associated with mortality on days 0 and 1 (p=0.018 and p=0.008, resp.. Conclusions. Our study illustrated that TG levels are associated with mortality in patients with sepsis. This may be attributable to alterations in serum lipid metabolism during sepsis, thus modulating the host response to inflammation in critically ill patients.

  19. Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection

    Directory of Open Access Journals (Sweden)

    Erica S. Lovelace

    2015-11-01

    Full Text Available Chronic viral infections like those caused by hepatitis C virus (HCV and human immunodeficiency virus (HIV cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA and keeping HIV viral loads below detection with antiretroviral therapy (ART, there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK and mechanistic target of rapamycin (mTOR, and these pathways directly influence cellular inflammatory status (such as NF-κB and immune function. Natural products represent a vast toolkit to dissect and define how cellular metabolism controls cellular immune and inflammatory function.

  20. The Alteration of Lipid Metabolism in Burkitt Lymphoma Identifies a Novel Marker: Adipophilin

    OpenAIRE

    Ambrosio, Maria R.; Piccaluga, Pier P.; Maurilio Ponzoni; Rocca, Bruno J; Valeria Malagnino; Monica Onorati; Giulia De Falco; Valeria Calbi; Martin Ogwang; Naresh, Kikkeri N.; Pileri, Stefano A.; Claudio Doglioni; Lorenzo Leoncini; Stefano Lazzi

    2012-01-01

    BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymp...

  1. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway

    OpenAIRE

    Lawn, Richard M.; Wade, David P.; Garvin, Michael R.; Wang, Xingbo; Schwartz, Karen; Porter, J. Gordon; Seilhamer, Jeffrey J.; Ashley M Vaughan; Oram, John F.

    1999-01-01

    The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC...

  2. Lipid Reconstitution-Enabled Formation of Gold Nanoparticle Clusters for Mimetic Cellular Membrane

    OpenAIRE

    Jiyoung Nam; Yong-Tae Kim; Aeyeon Kang; Kook-Han Kim; KyoRee Lee; Wan Soo Yun; Yong Ho Kim

    2016-01-01

    Gold nanoparticles (AuNPs) encapsulated within reconstituted phospholipid bilayers have been utilized in various bioapplications due to their improved cellular uptake without compromising their advantages. Studies have proved that clustering AuNPs can enhance the efficacy of theranostic effects, but controllable aggregation or oligomerization of AuNPs within lipid membranes is still challenging. Here, we successfully demonstrate the formation of gold nanoparticle clusters (AuCLs), supported b...

  3. Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the DNA Methylation Patterns of Genes Involved in Lipid Metabolism

    Science.gov (United States)

    Ke, Zhang-Hong; Pan, Jie-Xue; Jin, Lu-Yang; Xu, Hai-Yan; Yu, Tian-Tian; Ullah, Kamran; Rahman, Tanzil Ur; Ren, Jun; Cheng, Yi; Dong, Xin-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-08-01

    Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism is still unclear. Using a mouse BPA exposure model, we investigated the effects of long-term BPA exposure on lipid metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 μg BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic accumulation of triglycerides and cholesterol. The liver cells from the BPA-exposed mice showed significantly increased expression levels of the genes related to lipid synthesis. These liver cells showed decreased DNA methylation levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2 that may upregulate the genes related to lipid synthesis. The expression levels of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell line treated with BPA showed decreased expression levels of DNA methyltransferases and increased expression levels of genes involved in lipid synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and increased expression levels of genes involved in lipid synthesis. Our results suggest that long-term BPA exposure could induce hepatic lipid accumulation, which may be due to the epigenetic reprogramming of the genes involved in lipid metabolism, such as the alterations of DNA methylation patterns.

  4. FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

    OpenAIRE

    Nobuyuki Itoh; Morichika Konishi; Yusuke Murata

    2011-01-01

    The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell su...

  5. Transcriptome profile of liver at different physiological stages reveals potential mode for lipid metabolism in laying hens

    OpenAIRE

    Li, Hong; Wang, Taian; Xu, Chunlin; Wang, Dandan; Ren, Junxiao; Li, Yanmin; Tian, Yadong; Wang, Yanbin; Jiao, Yuping; Kang, Xiangtao; Liu, Xiaojun

    2015-01-01

    Background Liver is an important metabolic organ that plays a critical role in lipid synthesis, degradation, and transport; however, the molecular regulatory mechanisms of lipid metabolism remain unclear in chicken. In this study, RNA-Seq technology was used to investigate differences in expression profiles of hepatic lipid metabolism-related genes and associated pathways between juvenile and laying hens. The study aimed to broaden the understanding of liver lipid metabolism in chicken, and t...

  6. Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis

    Institute of Scientific and Technical Information of China (English)

    Umbreen Ahmed; Patricia S Latham; Phillip S Oates

    2012-01-01

    The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways.Although conflicting results have been obtained,most studies support the hypothesis that iron plays a role in hepatic lipogenesis.Iron is an integral part of some enzymes and transporters involved in lipid metabolism and,as such,may exert a direct effect on hepatic lipid load,intrahepatic metabolic pathways and hepatic lipid secretion.On the other hand,iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation,a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH).The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportin and the iron regulatory molecule hepcidin.The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH.More defined studies are required to improve our understanding of these effects.

  7. APOA2 Polymorphism in Relation to Obesity and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Moushira Erfan Zaki

    2013-01-01

    Full Text Available Objectives. This study aims to analysis the relationship between c.-492T>C polymorphism in APOA2 gene and the risk for obesity in a sample of Egyptian adolescents and investigates its effect on body fat distribution and lipid metabolism. Material and Methods. A descriptive, cross-sectional study was conducted on 303 adolescents. They were 196 obese and 107 nonobese, aged 16–19 years old. Variables examined included body mass index (BMI, waist circumference (WC, waist to hip ratio (WHR, systolic and diastolic blood pressure (BP, body fat percentage (BF%, abdominal visceral fat layer, and dietary intake. Abdominal visceral fat thickness was determined by ultrasonography. The polymorphism in the APOA2 c.-492T>C was analyzed by PCR amplification. Results. Genotype frequencies were in Hardy-Weinberg equilibrium. The frequency of the mutant C allele was significantly higher in obese cases compared to nonobese. After multivariate adjustment, waist, BF% and visceral adipose layer, food consumption, and HDL-C were significantly higher in homozygous allele CC carriers than TT+TC carriers. Conclusions. Homozygous individuals for the C allele had higher obesity risk than carriers of the T allele and had elevated levels of visceral adipose tissue and serum HDL-C. Moreover, the study shows association between the APOA2 c.-492T>C polymorphism and food consumption.

  8. Cellular Metabolic Network Analysis: Discovering Important Reactions in Treponema pallidum

    OpenAIRE

    Xueying Chen; Min Zhao; Hong Qu

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pall...

  9. A Role of Lipid Metabolism during Cumulus-Oocyte Complex Maturation: Impact of Lipid Modulators to Improve Embryo Production

    Directory of Open Access Journals (Sweden)

    E. G. Prates

    2014-01-01

    Full Text Available Oocyte intracellular lipids are mainly stored in lipid droplets (LD providing energy for proper growth and development. Lipids are also important signalling molecules involved in the regulatory mechanisms of maturation and hence in oocyte competence acquisition. Recent studies show that LD are highly dynamic organelles. They change their shape, volume, and location within the ooplasm as well as their interaction with other organelles during the maturation process. The droplets high lipid content has been correlated with impaired oocyte developmental competence and low cryosurvival. Yet the underlying mechanisms are not fully understood. In particular, the lipid-rich pig oocyte might be an excellent model to understand the role of lipids and fatty acid metabolism during the mammalian oocyte maturation and their implications on subsequent monospermic fertilization and preimplantation embryo development. The possibility of using chemical molecules to modulate the lipid content of oocytes and embryos to improve cryopreservation as well as its biological effects during development is here described. Furthermore, these principles of lipid content modulation may be applied not only to germ cells and embryo cryopreservation in livestock production but also to biomedical fundamental research.

  10. Role of a liver fatty acid-binding protein gene in lipid metabolism in chicken hepatocytes.

    Science.gov (United States)

    Gao, G L; Na, W; Wang, Y X; Zhang, H F; Li, H; Wang, Q G

    2015-01-01

    This study investigated the role of the chicken liver fatty acid-binding protein (L-FABP) gene in lipid metabolism in hepatocytes, and the regulatory relationships between L-FABP and genes related to lipid metabolism. The short hairpin RNA (shRNA) interference vector with L-FABP and an eukaryotic expression vector were used. Chicken hepatocytes were subjected to shRNA-mediated knockdown or L-FABP cDNA overexpression. Expression levels of lipid metabolism-related genes and biochemical parameters were detected 24, 36, 48, 60, and 72 h after transfection with the interference or overexpression plasmids for L-FABP, PPARα and L-BABP expression levels, and the total amount of cholesterol, were significantly affected by L-FABP expression. L-FABP may affect lipid metabolism by regulating PPARα and L-BABP in chicken hepatocytes. PMID:25966259

  11. Effects of gemfibrozil on lipid metabolism, steroidogenesis and reproduction in the fathead minnow (Pimephales promelas)

    Science.gov (United States)

    Fibrates are a class of pharmaceuticals that indirectly modulate cholesterol biosynthesis through effects on peroxisome proliferator-activated receptors (PPARs), which are transcriptional cofactors that regulate expression of genes related to lipid metabolism. Gemfibrozil is a fi...

  12. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    Science.gov (United States)

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  13. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  14. The effect of adropin on lipid and glucose metabolism in rats with hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Raziye Akcılar

    2016-03-01

    Conclusion: Adropin may ameliorate lipid metabolism, reduce insulin resistance, and inhibit hepatocytes inflammation. Thus, adropin had significant therapeutic benefits and could be suggested as a potential candidate agent against hyperlipidemia.

  15. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    Directory of Open Access Journals (Sweden)

    Rosa Castellano

    Full Text Available Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight were restrictively-fed diets providing either an adequate (CTRL or a deficient methionine supply (MD during 10 days (n=6 per group. At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently

  16. Cellular metabolic network analysis: discovering important reactions in Treponema pallidum.

    Science.gov (United States)

    Chen, Xueying; Zhao, Min; Qu, Hong

    2015-01-01

    T. pallidum, the syphilis-causing pathogen, performs very differently in metabolism compared with other bacterial pathogens. The desire for safe and effective vaccine of syphilis requests identification of important steps in T. pallidum's metabolism. Here, we apply Flux Balance Analysis to represent the reactions quantitatively. Thus, it is possible to cluster all reactions in T. pallidum. By calculating minimal cut sets and analyzing topological structure for the metabolic network of T. pallidum, critical reactions are identified. As a comparison, we also apply the analytical approaches to the metabolic network of H. pylori to find coregulated drug targets and unique drug targets for different microorganisms. Based on the clustering results, all reactions are further classified into various roles. Therefore, the general picture of their metabolic network is obtained and two types of reactions, both of which are involved in nucleic acid metabolism, are found to be essential for T. pallidum. It is also discovered that both hubs of reactions and the isolated reactions in purine and pyrimidine metabolisms play important roles in T. pallidum. These reactions could be potential drug targets for treating syphilis. PMID:26495292

  17. Dietary L-carnitine and energy and lipid metabolism in African catfish (Clarias gariepinus) juveniles

    OpenAIRE

    Ozorio, R.

    2001-01-01

    As the lipid content of the diet increases so does the requirement for certain components involved in lipid metabolism. Carnitine is a normal constituent of animal tissues and plasma, which is required for the transport of long-chain fatty acids (LCFAs) to the site of oxidation. To avoid accumulation of lipids, supplementation of dietary carnitine may be used to stimulate fatty acid oxidation and to regulate lipolysis. Previous studies have demonstrated that responses to carnitine administrat...

  18. Metabolomic profiles of lipid metabolism, arterial stiffness and hemodynamics in male coronary artery disease patients

    Directory of Open Access Journals (Sweden)

    Kaido Paapstel

    2016-06-01

    Conclusions: We demonstrated an independent association between the serum medium- and long-chain acylcarnitine profile and aortic stiffness for the CAD patients. In addition to the lipid-related classical CVD risk markers, the intermediates of lipid metabolism may serve as novel indicators for altered vascular function.

  19. Signals for the lysosome: a control center for cellular clearance and energy metabolism

    OpenAIRE

    Settembre, Carmine; Fraldi, Alessandro; Medina, Diego L.; Ballabio, Andrea

    2013-01-01

    For a long time lysosomes were considered merely to be cellular “incinerators” involved in the degradation and recycling of cellular waste. However, there is now compelling evidence indicating that lysosomes have a much broader function and that they are involved in fundamental processes such as secretion, plasma membrane repair, signaling and energy metabolism. Furthermore, the essential role of lysosomes in the autophagic pathway puts these organelles at the crossroads of several cellular p...

  20. Hormonal regulation of lipid metabolism in developing coho salmon, Oncorhynchus kisutch

    Energy Technology Data Exchange (ETDEWEB)

    Sheridan, M.A.

    1985-01-01

    Lipid metabolism in juvenile coho salmon is characterized, and adaptive changes in lipid mobilization are described in relation to development and hormonal influences. The rates of lipogenesis and lipolysis were determined in selected tissues of juvenile salmon during the period of seawater preadaptive development (smoltification). Neutral lipid (sterol) and fatty acid synthesis in the liver and mesenteric fat was measured by tritium incorporation. Fatty acid synthesis in the liver and mesenteric fat decreased by 88% and 81%, respectively, between late February (parr) and early June (smolt). To assess the role of hormones in smoltification-associated lipid depletion, growth hormone, prolactin, thyroxin and cortisol were administered in vivo early in development (parr) to determine if any of these factors could initiate the metabolic responses normally seen later in development (smolt). Growth hormone stimulated lipid mobilization from coho salmon parr. Prolactin strongly stimulated lipid mobilization in coho parr. Thyroxin and cortisol also stimulated lipid mobilization for coho salmon parr. The direct effect of hormones was studied by in vitro pH-stat incubation of liver slices. These data suggest that norepinephrine stimulates fatty acid release via ..beta..-adrenergic pathways. Somatostatin and its partial analogue from the fish caudal neurosecretory system, urotensin II, also affect lipid mobilization. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that the regulation of lipid metabolism in salmon involves both long-acting and short-acting hormonal agents.

  1. Hormonal regulation of lipid metabolism in developing coho salmon, Oncorhynchus kisutch

    International Nuclear Information System (INIS)

    Lipid metabolism in juvenile coho salmon is characterized, and adaptive changes in lipid mobilization are described in relation to development and hormonal influences. The rates of lipogenesis and lipolysis were determined in selected tissues of juvenile salmon during the period of seawater preadaptive development (smoltification). Neutral lipid (sterol) and fatty acid synthesis in the liver and mesenteric fat was measured by tritium incorporation. Fatty acid synthesis in the liver and mesenteric fat decreased by 88% and 81%, respectively, between late February (parr) and early June (smolt). To assess the role of hormones in smoltification-associated lipid depletion, growth hormone, prolactin, thyroxin and cortisol were administered in vivo early in development (parr) to determine if any of these factors could initiate the metabolic responses normally seen later in development (smolt). Growth hormone stimulated lipid mobilization from coho salmon parr. Prolactin strongly stimulated lipid mobilization in coho parr. Thyroxin and cortisol also stimulated lipid mobilization for coho salmon parr. The direct effect of hormones was studied by in vitro pH-stat incubation of liver slices. These data suggest that norepinephrine stimulates fatty acid release via β-adrenergic pathways. Somatostatin and its partial analogue from the fish caudal neurosecretory system, urotensin II, also affect lipid mobilization. These results establish the presence of hormone-sensitive lipase in salmon liver and suggest that the regulation of lipid metabolism in salmon involves both long-acting and short-acting hormonal agents

  2. Quantitative on-line monitoring of cellular glucose and lactate metabolism in vitro with slow perfusion

    NARCIS (Netherlands)

    Leegsma-Vogt, G; Venema, K; Brouwer, N; Gramsbergen, JB; Copray, S; Korf, J

    2004-01-01

    An on-line in vitro perfusion technique is described that allows the continuous quantification of cellular glucose metabolism in vitro. Using biosensor technology, we measure glucose and lactate metabolism at a minute-to-minute time resolution for periods up to several days. The application of our p

  3. Novel Anticancer Platinum(IV) Complexes with Adamantylamine: Their Efficiency and Innovative Chemotherapy Strategies Modifying Lipid Metabolism.

    Science.gov (United States)

    Kozubík, Alois; Vaculová, Alena; Soucek, Karel; Vondrácek, Jan; Turánek, Jaroslav; Hofmanová, Jirina

    2008-01-01

    The impressive impact of cisplatin on cancer on one side and severe side effects, as well as the development of drug resistance during treatment on the other side, were the factors motivating scientists to design and synthesize new more potent analogues lacking disadvantages of cisplatin. Platinum(IV) complexes represent one of the perspective groups of platinum-based drugs. In this review, we summarize recent findings on both in vitro and in vivo effects of platinum(IV) complexes with adamantylamine. Based on a literary overview of the mechanisms of activity of platinum-based cytostatics, we discuss opportunities for modulating the effects of novel platinum complexes through interactions with apoptotic signaling pathways and with cellular lipids, including modulations of the mitochondrial cell death pathway, oxidative stress, signaling of death ligands, lipid metabolism/signaling, or intercellular communication. These approaches might significantly enhance the efficacy of both novel and established platinum-based cytostatics. PMID:18414587

  4. Cellular Metabolic Rate Is Influenced by Life-History Traits in Tropical and Temperate Birds

    OpenAIRE

    Jimenez, Ana Gabriela; Van Brocklyn, James; Wortman, Matthew; Williams, Joseph B.

    2014-01-01

    In general, tropical birds have a “slow pace of life,” lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cel...

  5. Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

    International Nuclear Information System (INIS)

    Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

  6. Lipid metabolism in the heart. Contribution of BMIPP to the diseased heart

    Energy Technology Data Exchange (ETDEWEB)

    Nohara, Ryuji [Tazuke Kofukai Medical Research Inst., Osaka (Japan). Kitano Hospital

    2001-10-01

    Lipid contributes greatly in cardiac metabolism to produce high energy ATPs, and is suggested to be related to the progression and deterioration of heart disease. It is fortunate that the I-123-betamethyliodophenylpentadecanoic acid (BMIPP) imaging technique is now available in determining heart condition, but we must be cautious about the interpretation of images obtained with new tracer. From the uptake of BMIPP into the cell to breakdown and catabolism of it, there exist so many critical enzymatical pathways relating to the modification of BMIPP imaging. In clinical evaluation, the image will be translated as the integral effects of these pathways. In order words, we must be aware of these critical pathways regulating lipid metabolism and modifying factors in order to correctly understand BMIPP imaging. Lipid transport is affected by the albumin/FFA ratio in the blood, and extraction with membrane transporter proteins. Fatty acid binding protein (FABP) in the cytosole will play an important role in regulating lipid flux and following metabolism. Lipid will be utilized either for oxidation, triglyceride or phospholipid formation. For oxidation, carnitine palmitoil transferase is the key enzyme for the entrance of lipid into mitochondria, and oxidative enzymes such as acyl CoA dehydrogenase (MCAD, LCAD, HAD) will determine lipid use for the TCA cycle. ATPs produced in the mitochondria again limit the TG store. It is well known that BMIPP imaging completely changes in the ischemic condition, and is also shown that lipid metabolical regulation completely differs from normal in the very early phase of cardiac hypertrophy. In the process of deteriorating heart failure, metabolical switching of lipid with glucose will take place. In such a different heart disease conditions, it is clear that lipid metabolical regulation, including many lipid enzymes, works differently from in the healthy condition. These lipid enzymes are regulated by nuclear factor peroxisome

  7. Cellular metabolism regulates contact sites between vacuoles and mitochondria

    NARCIS (Netherlands)

    Hönscher, Carina; Mari, Muriel; Auffarth, Kathrin; Bohnert, Maria; Griffith, Janice; Geerts, Willie; van der Laan, Martin; Cabrera, Margarita; Reggiori, Fulvio; Ungermann, Christian

    2014-01-01

    Emerging evidence suggests that contact sites between different organelles form central hubs in the coordination of cellular physiology. Although recent work has emphasized the crucial role of the endoplasmic reticulum in interorganellar crosstalk, the cooperative behavior of other organelles is lar

  8. From Ancient Pathways to Aging Cells-Connecting Metabolism and Cellular Senescence.

    Science.gov (United States)

    Wiley, Christopher D; Campisi, Judith

    2016-06-14

    Cellular senescence is a complex stress response that permanently arrests the proliferation of cells at risk for oncogenic transformation. However, senescent cells can also drive phenotypes associated with aging. Although the senescence-associated growth arrest prevents the development of cancer, and the metabolism of cancer cells has been studied in depth, the metabolic causes and consequences of cellular senescence were largely unexplored until recently. New findings reveal key roles for several aspects of cellular metabolism in the establishment and control of senescent phenotypes. These discoveries have important implications for both cancer and aging. In this review, we highlight some of the recent links between metabolism and phenotypes that are commonly associated with senescent cells. PMID:27304503

  9. Action of Selenium Compounds on the Cellular Metabolism by Microcalorimetry

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A new method is introduced to study the action between biomaterials and organism.By using an LKB-2277 bioactivity monitor and ampoule method,the fundamental thermogenesis curves of the metabolic process of pk-15 and the toxic effect of three kinds of selenomorpholine compounds on it were studied at 37℃.From the thermogenesis curves,the heat released by pk-15 metabolism was calculated.The results show that the selenium compounds all have toxic action on the metabolism process of pk-15 at the range of experimental concentrations.The sequence of the toxic action of selenium compounds is:Na2SeO3>β-(N-selenomorpholine)-ethyl phenylketone hydrochloride>selenomorpholine.

  10. Cinnamon extract regulates intestinal lipid metabolism related gene expression in primary enterocytes of rats

    Science.gov (United States)

    Emerging evidence suggests that the small intestine is not a passive organ, but is actively involved in the regulation of lipid absorption, intracellular transport, and metabolism, and is closely linked to systemic lipoprotein metabolism. We have reported previously that the water-soluble components...

  11. Angiopoietin-Like Protein 4 and Postprandial Skeletal Muscle Lipid Metabolism in Overweight and Obese Prediabetics

    NARCIS (Netherlands)

    Kolk, van der Birgitta W.; Goossens, Gijs H.; Jocken, Johan W.; Kersten, Sander; Blaak, Ellen E.

    2016-01-01

    Context: Angiopoietin-like protein 4 (ANGPTL4) decreases plasma triacylglycerol (TAG) clearance by inhibiting lipoprotein lipase (LPL) and may contribute to impairments in lipid metabolism under compromised metabolic conditions. Objectives: To investigate the effects of a high-saturated fatty acid (

  12. Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders

    Directory of Open Access Journals (Sweden)

    Messina Vincenzo

    2011-10-01

    Full Text Available Abstract Objective To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI as a new possible biomarker. Methods 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs. The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision (DSM-IV-TR official/appendix criteria]. The levels of the cholesterol, triglycerides and apolipoproteins A and B were determined. The LI, for each subject, was obtained through a mathematical operation on the values of the cholesterol and triglycerides levels compared with the maximum cut-off of the general population. The autonomic functioning was tested with Ewing battery tests. Particularly, the correlation between heart rate variability (HRV and lipid metabolism has been investigated. Results Pathological and control groups, compared among each other, presented some peculiarities in the lipid metabolism and the autonomic dysfunction scores. In addition, a statistically significant correlation has been found between HRV and lipid metabolism. Conclusions Lipid metabolism and autonomic functioning seem to be related to the discussed psychiatric disorders. LI, in addition, could represent a new possible biomarker to be considered.

  13. Understanding the control of acyl flux through the lipid metabolic network of plant oil biosynthesis.

    Science.gov (United States)

    Bates, Philip D

    2016-09-01

    Plant oil biosynthesis involves a complex metabolic network with multiple subcellular compartments, parallel pathways, cycles, and pathways that have a dual function to produce essential membrane lipids and triacylglycerol. Modern molecular biology techniques provide tools to alter plant oil compositions through bioengineering, however with few exceptions the final composition of triacylglycerol cannot be predicted. One reason for limited success in oilseed bioengineering is the inadequate understanding of how to control the flux of fatty acids through various fatty acid modification, and triacylglycerol assembly pathways of the lipid metabolic network. This review focuses on the mechanisms of acyl flux through the lipid metabolic network, and highlights where uncertainty resides in our understanding of seed oil biosynthesis. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID:27003249

  14. Remodeling lipid metabolism and improving insulin responsiveness in human primary myotubes.

    Directory of Open Access Journals (Sweden)

    Lauren M Sparks

    Full Text Available OBJECTIVE: Disturbances in lipid metabolism are strongly associated with insulin resistance and type 2 diabetes (T2D. We hypothesized that activation of cAMP/PKA and calcium signaling pathways in cultured human myotubes would provide further insight into regulation of lipid storage, lipolysis, lipid oxidation and insulin responsiveness. METHODS: Human myoblasts were isolated from vastus lateralis, purified, cultured and differentiated into myotubes. All cells were incubated with palmitate during differentiation. Treatment cells were pulsed 1 hour each day with forskolin and ionomycin (PFI during the final 3 days of differentiation to activate the cAMP/PKA and calcium signaling pathways. Control cells were not pulsed (control. Mitochondrial content, (14C lipid oxidation and storage were measured, as well as lipolysis and insulin-stimulated glycogen storage. Myotubes were stained for lipids and gene expression measured. RESULTS: PFI increased oxidation of oleate and palmitate to CO(2 (p<0.001, isoproterenol-stimulated lipolysis (p = 0.01, triacylglycerol (TAG storage (p<0.05 and mitochondrial DNA copy number (p = 0.01 and related enzyme activities. Candidate gene and microarray analysis revealed increased expression of genes involved in lipolysis, TAG synthesis and mitochondrial biogenesis. PFI increased the organization of lipid droplets along the myofibrillar apparatus. These changes in lipid metabolism were associated with an increase in insulin-mediated glycogen storage (p<0.001. CONCLUSIONS: Activation of cAMP/PKA and calcium signaling pathways in myotubes induces a remodeling of lipid droplets and functional changes in lipid metabolism. These results provide a novel pharmacological approach to promote lipid metabolism and improve insulin responsiveness in myotubes, which may be of therapeutic importance for obesity and type 2 diabetes.

  15. ABCC6 : a new player in cellular cholesterol and lipoprotein metabolism?

    OpenAIRE

    Kuzaj, Patricia; Kuhn, Joachim; Dabisch-Ruthe, Mareike; Faust, Isabel; Götting, Christian; Knabbe, Cornelius; Hendig, Doris

    2014-01-01

    Background Dysregulations in cholesterol and lipid metabolism have been linked to human diseases like hypercholesterolemia, atherosclerosis or the metabolic syndrome. Many ABC transporters are involved in trafficking of metabolites derived from these pathways. Pseudoxanthoma elasticum (PXE), an autosomal-recessive disease caused by ABCC6 mutations, is characterized by atherogenesis and soft tissue calcification. Methods In this study we investigated the regulation of cholesterol biosynthesis ...

  16. Regulatory mechanisms underlying oil palm fruit mesocarp maturation, ripening, and functional specialization in lipid and carotenoid metabolism.

    Science.gov (United States)

    Tranbarger, Timothy J; Dussert, Stéphane; Joët, Thierry; Argout, Xavier; Summo, Marilyne; Champion, Antony; Cros, David; Omore, Alphonse; Nouy, Bruno; Morcillo, Fabienne

    2011-06-01

    Fruit provide essential nutrients and vitamins for the human diet. Not only is the lipid-rich fleshy mesocarp tissue of the oil palm (Elaeis guineensis) fruit the main source of edible oil for the world, but it is also the richest dietary source of provitamin A. This study examines the transcriptional basis of these two outstanding metabolic characters in the oil palm mesocarp. Morphological, cellular, biochemical, and hormonal features defined key phases of mesocarp development. A 454 pyrosequencing-derived transcriptome was then assembled for the developmental phases preceding and during maturation and ripening, when high rates of lipid and carotenoid biosynthesis occur. A total of 2,629 contigs with differential representation revealed coordination of metabolic and regulatory components. Further analysis focused on the fatty acid and triacylglycerol assembly pathways and during carotenogenesis. Notably, a contig similar to the Arabidopsis (Arabidopsis thaliana) seed oil transcription factor WRINKLED1 was identified with a transcript profile coordinated with those of several fatty acid biosynthetic genes and the high rates of lipid accumulation, suggesting some common regulatory features between seeds and fruits. We also focused on transcriptional regulatory networks of the fruit, in particular those related to ethylene transcriptional and GLOBOSA/PISTILLATA-like proteins in the mesocarp and a central role for ethylene-coordinated transcriptional regulation of type VII ethylene response factors during ripening. Our results suggest that divergence has occurred in the regulatory components in this monocot fruit compared with those identified in the dicot tomato (Solanum lycopersicum) fleshy fruit model. PMID:21487046

  17. Ectopic lipid deposition and the metabolic profile of skeletal muscle in ovariectomized mice

    OpenAIRE

    Jackson, Kathryn C.; Wohlers, Lindsay M.; Richard M. Lovering; Schuh, Rosemary A.; Maher, Amy C.; Bonen, Arend; Koves, Timothy R.; Ilkayeva, Olga; Thomson, David M.; Muoio, Deborah M.; Spangenburg, Espen E.

    2012-01-01

    Disruptions of ovarian function in women are associated with increased risk of metabolic disease due to dysregulation of peripheral glucose homeostasis in skeletal muscle. Our previous evidence suggests that alterations in skeletal muscle lipid metabolism coupled with altered mitochondrial function may also develop. The objective of this study was to use an integrative metabolic approach to identify potential areas of dysfunction that develop in skeletal muscle from ovariectomized (OVX) femal...

  18. Lipid droplets as fat storage organelles in Caenorhabditis elegans: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man

    OpenAIRE

    Mak, Ho Yi

    2012-01-01

    Lipid droplets are evolutionarily conserved organelles where cellular fat storage and mobilization are exquisitely regulated. Recent studies have defined lipid droplets in C. elegans and explored how they are regulated by genetic and dietary factors. C. elegans offers unique opportunities to visualize lipid droplets at single-cell resolution in live animals. The development of novel microscopy techniques and protein markers for lipid droplets will accelerate studies on how nutritional states ...

  19. The orchestra of lipid-transfer proteins at the crossroads between metabolism and signaling.

    Science.gov (United States)

    Chiapparino, Antonella; Maeda, Kenji; Turei, Denes; Saez-Rodriguez, Julio; Gavin, Anne-Claude

    2016-01-01

    Within the eukaryotic cell, more than 1000 species of lipids define a series of membranes essential for cell function. Tightly controlled systems of lipid transport underlie the proper spatiotemporal distribution of membrane lipids, the coordination of spatially separated lipid metabolic pathways, and lipid signaling mediated by soluble proteins that may be localized some distance away from membranes. Alongside the well-established vesicular transport of lipids, non-vesicular transport mediated by a group of proteins referred to as lipid-transfer proteins (LTPs) is emerging as a key mechanism of lipid transport in a broad range of biological processes. More than a hundred LTPs exist in humans and these can be divided into at least ten protein families. LTPs are widely distributed in tissues, organelles and membrane contact sites (MCSs), as well as in the extracellular space. They all possess a soluble and globular domain that encapsulates a lipid monomer and they specifically bind and transport a wide range of lipids. Here, we present the most recent discoveries in the functions and physiological roles of LTPs, which have expanded the playground of lipids into the aqueous spaces of cells. PMID:26658141

  20. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  1. Cellular metabolic rate is influenced by life-history traits in tropical and temperate birds.

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Jimenez

    Full Text Available In general, tropical birds have a "slow pace of life," lower rates of whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding of how variation in life-history at the whole-organism level might be linked to cellular function. Because tropical birds have lower rates of whole-animal metabolism, we hypothesized that cells from tropical species would also have lower rates of cellular metabolism than cells from temperate species of similar body size and common phylogenetic history. We cultured primary dermal fibroblasts from 17 tropical and 17 temperate phylogenetically-paired species of birds in a common nutritive and thermal environment and then examined basal, uncoupled, and non-mitochondrial cellular O2 consumption (OCR, proton leak, and anaerobic glycolysis (extracellular acidification rates [ECAR], using an XF24 Seahorse Analyzer. We found that multiple measures of metabolism in cells from tropical birds were significantly lower than their temperate counterparts. Basal and uncoupled cellular metabolism were 29% and 35% lower in cells from tropical birds, respectively, a decrease closely aligned with differences in whole-animal metabolism between tropical and temperate birds. Proton leak was significantly lower in cells from tropical birds compared with cells from temperate birds. Our results offer compelling evidence that whole-animal metabolism is linked to cellular respiration as a function of an animal's life-history evolution. These findings are consistent with the idea that natural selection has uniquely fashioned cells of long-lived tropical bird species to have lower rates of metabolism than cells from shorter-lived temperate species.

  2. Alkalizing reactions streamline cellular metabolism in acidogenic microorganisms.

    Directory of Open Access Journals (Sweden)

    Stefania Arioli

    Full Text Available An understanding of the integrated relationships among the principal cellular functions that govern the bioenergetic reactions of an organism is necessary to determine how cells remain viable and optimise their fitness in the environment. Urease is a complex enzyme that catalyzes the hydrolysis of urea to ammonia and carbonic acid. While the induction of urease activity by several microorganisms has been predominantly considered a stress-response that is initiated to generate a nitrogen source in response to a low environmental pH, here we demonstrate a new role of urease in the optimisation of cellular bioenergetics. We show that urea hydrolysis increases the catabolic efficiency of Streptococcus thermophilus, a lactic acid bacterium that is widely used in the industrial manufacture of dairy products. By modulating the intracellular pH and thereby increasing the activity of β-galactosidase, glycolytic enzymes and lactate dehydrogenase, urease increases the overall change in enthalpy generated by the bioenergetic reactions. A cooperative altruistic behaviour of urease-positive microorganisms on the urease-negative microorganisms within the same environment was also observed. The physiological role of a single enzymatic activity demonstrates a novel and unexpected view of the non-transcriptional regulatory mechanisms that govern the bioenergetics of a bacterial cell, highlighting a new role for cytosol-alkalizing biochemical pathways in acidogenic microorganisms.

  3. Alkalizing Reactions Streamline Cellular Metabolism in Acidogenic Microorganisms

    Science.gov (United States)

    Arioli, Stefania; Ragg, Enzio; Scaglioni, Leonardo; Fessas, Dimitrios; Signorelli, Marco; Karp, Matti; Daffonchio, Daniele; De Noni, Ivano; Mulas, Laura; Oggioni, Marco; Guglielmetti, Simone; Mora, Diego

    2010-01-01

    An understanding of the integrated relationships among the principal cellular functions that govern the bioenergetic reactions of an organism is necessary to determine how cells remain viable and optimise their fitness in the environment. Urease is a complex enzyme that catalyzes the hydrolysis of urea to ammonia and carbonic acid. While the induction of urease activity by several microorganisms has been predominantly considered a stress-response that is initiated to generate a nitrogen source in response to a low environmental pH, here we demonstrate a new role of urease in the optimisation of cellular bioenergetics. We show that urea hydrolysis increases the catabolic efficiency of Streptococcus thermophilus, a lactic acid bacterium that is widely used in the industrial manufacture of dairy products. By modulating the intracellular pH and thereby increasing the activity of β-galactosidase, glycolytic enzymes and lactate dehydrogenase, urease increases the overall change in enthalpy generated by the bioenergetic reactions. A cooperative altruistic behaviour of urease-positive microorganisms on the urease-negative microorganisms within the same environment was also observed. The physiological role of a single enzymatic activity demonstrates a novel and unexpected view of the non-transcriptional regulatory mechanisms that govern the bioenergetics of a bacterial cell, highlighting a new role for cytosol-alkalizing biochemical pathways in acidogenic microorganisms. PMID:21152088

  4. Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

    Directory of Open Access Journals (Sweden)

    Blanca Estela Ríos-González

    2014-01-01

    Full Text Available Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP. We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591 with blood pressure and lipid values in Mexican hypertensive (HT patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; P=0.001 under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.

  5. FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

    Science.gov (United States)

    Murata, Yusuke; Konishi, Morichika; Itoh, Nobuyuki

    2011-01-01

    The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases. PMID:21331285

  6. FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

    Directory of Open Access Journals (Sweden)

    Yusuke Murata

    2011-01-01

    Full Text Available The FGF family comprises twenty-two structurally related proteins with functions in development and metabolism. The Fgf21 gene was generated early in vertebrate evolution. FGF21 acts as an endocrine regulator in lipid metabolism. Hepatic Fgf21 expression is markedly induced in mice by fasting or a ketogenic diet. Experiments with Fgf21 transgenic mice and cultured cells indicate that FGF21 exerts pharmacological effects on glucose and lipid metabolism in hepatocytes and adipocytes via cell surface FGF receptors. However, experiments with Fgf21 knockout mice indicate that FGF21 inhibits lipolysis in adipocytes during fasting and attenuates torpor induced by a ketogenic diet but maybe not a physiological regulator for these hepatic functions. These findings suggest the pharmacological effects to be distinct from the physiological roles. Serum FGF21 levels are increased in patients with metabolic diseases having insulin resistance, indicating that FGF21 is a metabolic regulator and a biomarker for these diseases.

  7. Impaired lipid metabolism in idiopathic pulmonary alveolar proteinosis

    Directory of Open Access Journals (Sweden)

    Xu Wenbing

    2011-04-01

    Full Text Available Abstract Background It is well known that lipids abnormally accumulate in the alveoli during idiopathic pulmonary alveolar proteinosis (PAP. It is unclear, however, whether lipids also abnormally accumulate in serum. This study investigated the serum lipid panels in idiopathic PAP patients and explored the relationships between serum levels and the severity of idiopathic PAP. Methods and Results Clinical data including the level of serum lipids were evaluated in 33 non-diabetic idiopathic PAP patients and 157 healthy volunteers. Serum levels of triglyceride were higher in PAP patients than in healthy subjects (median: 192.00 mg/dl (P25: 104.36, P75: 219.00 vs 119.56 mg/dl (P25: 78.81, P75: 193.03, P vs 51.34 ± 12.06 mg/dl, P 2 (r = -0.403, P P Conclusions PAP associates with high triglyceride and low HDL levels in the serum, and these lipids provide potential intervention strategy for treatment.

  8. LMNA Mutations, Skeletal Muscle Lipid Metabolism, and Insulin Resistance

    OpenAIRE

    Boschmann, M.; Engeli, S; Moro, C.; A Luedtke; Adams, F.; Gorzelniak, K; G Rahn; A Mdhler; Dobberstein, K.; A Kr'ger; S. Schmidt; Spuler, S.; Luft, F. C.; Smith, S.R.; Schmidt, H. H.

    2010-01-01

    Context: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated.

  9. Unraveling algal lipid metabolism: Recent advances in gene identification.

    Science.gov (United States)

    Khozin-Goldberg, Inna; Cohen, Zvi

    2011-01-01

    Microalgae are now the focus of intensive research due to their potential as a renewable feedstock for biodiesel. This research requires a thorough understanding of the biochemistry and genetics of these organisms' lipid-biosynthesis pathways. Genes encoding lipid-biosynthesis enzymes can now be identified in the genomes of various eukaryotic microalgae. However, an examination of the predicted proteins at the biochemical and molecular levels is mandatory to verify their function. The essential molecular and genetic tools are now available for a comprehensive characterization of genes coding for enzymes of the lipid-biosynthesis pathways in some algal species. This review mainly summarizes the novel information emerging from recently obtained algal gene identification. PMID:20709142

  10. Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins.

    Science.gov (United States)

    Yamaji, Toshiyuki; Hanada, Kentaro

    2015-02-01

    In recent decades, many sphingolipid enzymes, sphingolipid-metabolism regulators and sphingolipid transfer proteins have been isolated and characterized. This review will provide an overview of the intracellular localization and topology of sphingolipid enzymes in mammalian cells to highlight the locations where respective sphingolipid species are produced. Interestingly, three sphingolipids that reside or are synthesized in cytosolic leaflets of membranes (ceramide, glucosylceramide and ceramide-1-phosphate) all have cytosolic lipid transfer proteins (LTPs). These LTPs consist of ceramide transfer protein (CERT), four-phosphate adaptor protein 2 (FAPP2) and ceramide-1-phosphate transfer protein (CPTP), respectively. These LTPs execute functions that affect both the location and metabolism of the lipids they bind. Molecular details describing the mechanisms of regulation of LTPs continue to emerge and reveal a number of critical processes, including competing phosphorylation and dephosphorylation reactions and binding interactions with regulatory proteins and lipids that influence the transport, organelle distribution and metabolism of sphingolipids. PMID:25382749

  11. Autonomic nervous system and lipid metabolism: findings in anxious-depressive spectrum and eating disorders

    OpenAIRE

    Messina Vincenzo; Luca Antonina; De Luca Maria; Pistorio Elisabetta; Calandra Carmela

    2011-01-01

    Abstract Objective To correlate lipid metabolism and autonomic dysfunction with anxious-depressive spectrum and eating disorders. To propose the lipid index (LI) as a new possible biomarker. Methods 95 patients and 60 controls were enrolled from the University Psychiatry Unit of Catania and from general practitioners (GPs). The patients were divided into four pathological groups: Anxiety, Depression, Anxious-Depressive Disorder and Eating Disorders [Diagnostic and Statistical Manual of Mental...

  12. Detrimental effects of fluvastatin on plasma lipid metabolism in rat breast carcinoma model

    OpenAIRE

    Kapinová Andrea; Kubatka P.; Žihlavniková Katarína; Stollárová Nadežda; Péč M.; Dobrota D.; Bojková Bianka; Kassayová Monika; Orendáš P.

    2013-01-01

    From clinical practice, obvious positive effects of statins on plasma lipid metabolism are well known. On the other hand, there are several experimental rodent studies, where these beneficial effects were not confirmed. The effects of fluvastatin on selected serum lipid parameters in a rat model of experimental breast cancer were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. At the end of the study (experiment dura...

  13. The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

    Science.gov (United States)

    Morris, Gerwyn; Walder, Ken; Puri, Basant K; Berk, Michael; Maes, Michael

    2016-09-01

    Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer's and Parkinson's disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling. PMID:26310971

  14. Skeletal muscle lipid metabolism in exercise and insulin resistance

    DEFF Research Database (Denmark)

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

  15. GIM3E: Condition-specific Models of Cellular Metabolism Developed from Metabolomics and Expression Data

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Brian; Ebrahim, Ali; Metz, Thomas O.; Adkins, Joshua N.; Palsson, Bernard O.; Hyduke, Daniel R.

    2013-11-15

    Motivation: Genome-scale metabolic models have been used extensively to investigate alterations in cellular metabolism. The accuracy of these models to represent cellular metabolism in specific conditions has been improved by constraining the model with omics data sources. However, few practical methods for integrating metabolomics data with other omics data sources into genome-scale models of metabolism have been reported. Results: GIMMME (Gene Inactivation Moderated by Metabolism, Metabolomics, and Expression) is an algorithm that enables the development of condition-specific models based on an objective function, transcriptomics, and intracellular metabolomics data. GIMMME establishes metabolite utilization requirements with metabolomics data, uses model-paired transcriptomics data to find experimentally supported solutions, and also provides calculations of the turnover (production / consumption) flux of metabolites. GIMMME was employed to investigate the effects of integrating additional omics datasets to create increasingly constrained solution spaces of Salmonella Typhimurium metabolism during growth in both rich and virulence media. This integration proved to be informative and resulted in a requirement of additional active reactions (12 in each case) or metabolites (26 or 29, respectively). The addition of constraints from transcriptomics also impacted the allowed solution space, and the cellular metabolites with turnover fluxes that were necessarily altered by the change in conditions increased from 118 to 271 of 1397. Availability: GIMMME has been implemented in Python and requires a COBRApy 0.2.x. The algorithm and sample data described here are freely available at: http://opencobra.sourceforge.net/

  16. Influence of difenoconazole on lipid metabolism in marine medaka (Oryzias melastigma).

    Science.gov (United States)

    Dong, Xiaocui; Li, Yan; Zhang, Lemeng; Zuo, Zhenghong; Wang, Chonggang; Chen, Meng

    2016-07-01

    Difenoconazole (DFZ) is a triazole fungicide that inhibits the biosynthesis of sterols in cell membranes and is widely used in agriculture for effectively treating fungal infections. However, there are few studies available addressing the effects of DFZ on lipid metabolism in marine fishes. The present study was conducted to investigate the effects of DFZ on lipid metabolism in marine medaka (Oryzias melastigma). After exposure to 1, 10, 100 and 1000 ng/L DFZ for 180 days, an increase in condition factor (CF), total lipids and polyunsaturated fatty acids (PUFA) contents accompanied with a decrease in saturated fatty acids was observed in the muscle of DFZ-exposed fish. The expression of peroxisome proliferator-activated receptor γ as well as retinoid X receptors in the muscle was up-regulated, which would be responsible for the lipid accumulation in the muscle. The elevation of Δ6-desaturase (FADS2) and Δ9-desaturase (SCD) mRNA levels in the muscle and liver might result in the increase of PUFA content. The increased CF index and total lipid amounts indicated that DFZ exposure could affect the health of fish. ∑SFA (sum of saturated fatty acids) and DHA (docosahexaenoic acid; 22:6n-3) concentrations decreased, and the levels of ∑PUFA and ∑n-6PUFA increased in the muscle, which suggested that DFZ exposure could change lipid metabolism and profiles in fish. PMID:27112457

  17. Cellular electron transfer and radical mechanisms for drug metabolism

    International Nuclear Information System (INIS)

    Aerobic and anaerobic reductions of various nitroaromatic compounds by mammalian cells result in the production of reactive intermediates. Drug reduction is dependent upon glucose, nonprotein thiols, endogenous enzyme levels, and drug electron affinity. Drugs with electron affinities approaching that of oxygen are reduced, in the presence of oxygen, beyond a one-electron radical anion. Nitroaromatic radical anion inactivation occurs by reaction with cellular ferricytochrome c, endogenous thiols, and with oxygen. In the latter case the reaction results in the production of peroxide. Drugs that are substrates for the enzyme glutathione-S-transferase remove endogeneous thiols and demonstrate peroxide production without prior thiol removal. Less electron affinic drugs such as misonidazole require thiol removal as well as the presence of cyanide or azide for maximal peroxide production. Under anaerobic conditions radical anion and nitroso intermediates are reactive with glutathione. Removal of endogenous thiols by hypoxic preincubation with misonidazole may be related to the enhanced radiation response and cytotoxicity of this drug. Reduction of nitro compounds in the presence of DNA and chemicals such as dithionite, zinc dust, or polarographic techniques causes binding to macromolecules and DNA breaks. Chemical-reduction of nitro compounds by ascorbate in the presence of cells enhances drug cytotoxic effects

  18. Regulation of glucose and lipid metabolism by dietary carbohydrate levels and lipid sources in gilthead sea bream juveniles.

    Science.gov (United States)

    Castro, Carolina; Corraze, Geneviève; Firmino-Diógenes, Alexandre; Larroquet, Laurence; Panserat, Stéphane; Oliva-Teles, Aires

    2016-07-01

    The long-term effects on growth performance, body composition, plasma metabolites, liver and intestine glucose and lipid metabolism were assessed in gilthead sea bream juveniles fed diets without carbohydrates (CH-) or carbohydrate-enriched (20 % gelatinised starch, CH+) combined with two lipid sources (fish oil; or vegetable oil (VO)). No differences in growth performance among treatments were observed. Carbohydrate intake was associated with increased hepatic transcripts of glucokinase but not of 6-phosphofructokinase. Expression of phosphoenolpyruvate carboxykinase was down-regulated by carbohydrate intake, whereas, unexpectedly, glucose 6-phosphatase was up-regulated. Lipogenic enzyme activities (glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase) and ∆6 fatty acyl desaturase (FADS2) transcripts were increased in liver of fish fed CH+ diets, supporting an enhanced potential for lipogenesis and long-chain PUFA (LC-PUFA) biosynthesis. Despite the lower hepatic cholesterol content in CH+ groups, no influence on the expression of genes related to cholesterol efflux (ATP-binding cassette G5) and biosynthesis (lanosterol 14 α-demethylase, cytochrome P450 51 cytochrome P450 51 (CYP51A1); 7-dehydrocholesterol reductase) was recorded at the hepatic level. At the intestinal level, however, induction of CYP51A1 transcripts by carbohydrate intake was recorded. Dietary VO led to decreased plasma phospholipid and cholesterol concentrations but not on the transcripts of proteins involved in phospholipid biosynthesis (glycerol-3-phosphate acyltransferase) and cholesterol metabolism at intestinal and hepatic levels. Hepatic and muscular fatty acid profiles reflected that of diets, despite the up-regulation of FADS2 transcripts. Overall, this study demonstrated that dietary carbohydrates mainly affected carbohydrate metabolism, lipogenesis and LC-PUFA biosynthesis, whereas effects of dietary lipid source were mostly related with tissue fatty acid composition

  19. 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...... 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...

  20. High-calorie diet partially ameliorates dysregulation of intrarenal lipid metabolism in remnant kidney

    OpenAIRE

    Kim, Hyun Ju; Yuan, Jun; Norris, Keith; Vaziri, Nosratola D.

    2009-01-01

    Chronic renal failure (CRF) is associated with malnutrition and renal tissue accumulation of lipids, which can contribute to progression of renal disease. This study was designed to explore the effect of a high-calorie diet on pathways involved in lipid metabolism in the remnant kidney of rats with CRF. 5/6 nephrectomized rats were randomized to receive a regular diet (3.0 kcal/g) or a high-calorie diet (4.5 kcal/g) for 12 weeks. Renal lipid contents and abundance of molecules involved in cho...

  1. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism.

    Directory of Open Access Journals (Sweden)

    Sebastiano Collino

    Full Text Available The aging phenotype in humans has been thoroughly studied but a detailed metabolic profiling capable of shading light on the underpinning biological processes of longevity is still missing. Here using a combined metabonomics approach compromising holistic (1H-NMR profiling and targeted MS approaches, we report for the first time the metabolic phenotype of longevity in a well characterized human aging cohort compromising mostly female centenarians, elderly, and young individuals. With increasing age, targeted MS profiling of blood serum displayed a marked decrease in tryptophan concentration, while an unique alteration of specific glycerophospholipids and sphingolipids are seen in the longevity phenotype. We hypothesized that the overall lipidome changes specific to longevity putatively reflect centenarians' unique capacity to adapt/respond to the accumulating oxidative and chronic inflammatory conditions characteristic of their extreme aging phenotype. Our data in centenarians support promotion of cellular detoxification mechanisms through specific modulation of the arachidonic acid metabolic cascade as we underpinned increased concentration of 8,9-EpETrE, suggesting enhanced cytochrome P450 (CYP enzyme activity. Such effective mechanism might result in the activation of an anti-oxidative response, as displayed by decreased circulating levels of 9-HODE and 9-oxoODE, markers of lipid peroxidation and oxidative products of linoleic acid. Lastly, we also revealed that the longevity process deeply affects the structure and composition of the human gut microbiota as shown by the increased extrection of phenylacetylglutamine (PAG and p-cresol sulfate (PCS in urine of centenarians. Together, our novel approach in this representative Italian longevity cohort support the hypothesis that a complex remodeling of lipid, amino acid metabolism, and of gut microbiota functionality are key regulatory processes marking exceptional longevity in humans.

  2. Comprehensive insights into microcystin-LR effects on hepatic lipid metabolism using cross-omics technologies.

    Science.gov (United States)

    Zhang, Zongyao; Zhang, Xu-Xiang; Wu, Bing; Yin, Jinbao; Yu, Yunjiang; Yang, Liuyan

    2016-09-01

    Microcystin-LR (MC-LR) can induce hepatic tissue damages and molecular toxicities, but its effects on lipid metabolism remain unknown. This study investigated the effects of MC-LR exposure on mice lipid metabolism and uncovered the underlying mechanism through metabonomic, transcriptomic and metagenomic analyses after administration of mice with MC-LR by gavage for 28 d. Increased liver weight and abdominal fat weight, and evident hepatic lipid vacuoles accumulation were observed in the mice fed with 0.2mg/kg/d MC-LR. Serum nuclear magnetic resonance analysis showed that MC-LR treatment altered the levels of serum metabolites including triglyceride, unsaturated fatty acid (UFA) and very low density lipoprotein. Digital Gene Expression technology was used to reveal differential expression of hepatic transcriptomes, demonstrating that MC-LR treatment disturbed hepatic UFA biosynthesis and activated peroxisome proliferator-activated receptor (PPAR) signaling pathways via Pparγ, Fabp1 and Fabp2 over-expression. Metagenomic analyses of gut microbiota revealed that MC-LR exposure also increased abundant ratio of Firmicutes vs. Bacteroidetes in gut and altered biosynthetic pathways of various microbial metabolic and pro-inflammatory molecules. In conclusion, oral MC-LR exposure can induce hepatic lipid metabolism disorder mediated by UFA biosynthesis and PPAR activation, and gut microbial community shift may play an important role in the metabolic disturbance. PMID:27208774

  3. A new fluorescence-based method identifies protein phosphatases regulating lipid droplet metabolism.

    Directory of Open Access Journals (Sweden)

    Bruno L Bozaquel-Morais

    Full Text Available In virtually every cell, neutral lipids are stored in cytoplasmic structures called lipid droplets (LDs and also referred to as lipid bodies or lipid particles. We developed a rapid high-throughput assay based on the recovery of quenched BODIPY-fluorescence that allows to quantify lipid droplets. The method was validated by monitoring lipid droplet turnover during growth of a yeast culture and by screening a group of strains deleted in genes known to be involved in lipid metabolism. In both tests, the fluorimetric assay showed high sensitivity and good agreement with previously reported data using microscopy. We used this method for high-throughput identification of protein phosphatases involved in lipid droplet metabolism. From 65 yeast knockout strains encoding protein phosphatases and its regulatory subunits, 13 strains revealed to have abnormal levels of lipid droplets, 10 of them having high lipid droplet content. Strains deleted for type I protein phosphatases and related regulators (ppz2, gac1, bni4, type 2A phosphatase and its related regulator (pph21 and sap185, type 2C protein phosphatases (ptc1, ptc4, ptc7 and dual phosphatases (pps1, msg5 were catalogued as high-lipid droplet content strains. Only reg1, a targeting subunit of the type 1 phosphatase Glc7p, and members of the nutrient-sensitive TOR pathway (sit4 and the regulatory subunit sap190 were catalogued as low-lipid droplet content strains, which were studied further. We show that Snf1, the homologue of the mammalian AMP-activated kinase, is constitutively phosphorylated (hyperactive in sit4 and sap190 strains leading to a reduction of acetyl-CoA carboxylase activity. In conclusion, our fast and highly sensitive method permitted us to catalogue protein phosphatases involved in the regulation of LD metabolism and present evidence indicating that the TOR pathway and the SNF1/AMPK pathway are connected through the Sit4p-Sap190p pair in the control of lipid droplet biogenesis.

  4. Effect of Cyolane on carbohydrate and lipid metabolism in rat

    International Nuclear Information System (INIS)

    Cyolane was orally administrated daily for 1-5 weeks (1 mg/kg body weight), induced a marked increase in liver glycogen content reaching its highest values after 1,2,3 and 15 weeks. In kidney and brain the glycogen contents showed a significant increase after 10, 12 and 15 weeks of intoxication. Serum glucose content was increased after 2, 3 and 8 weeks. It has been found that Cyolane caused a fluctuation in liver, kidney and brain total lipid through the first 8 weeks, thereafter it exhibited a significant increase after 10, 12 and 15 weeks. Serum total lipid exhibited a highly significant increase after 2-12 weeks, reaching its maximum value (288.66%) after 15 weeks. 3 figs., 4 tabs

  5. Regulation of exercise-induced lipid metabolism in skeletal muscle

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting; Kiens, Bente

    2014-01-01

    binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle...... mice. In skeletal muscle, 98% of the lipase activity is accounted for by adipose triglyceride lipase and hormone-sensitive lipase. Give that inhibition or knockout of hormone-sensitive lipase does not impair lipolysis in muscle during contraction, the data point to an important role of adipose......Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid...

  6. The effect of hypokinesia on lipid metabolism in adipose tissue

    Science.gov (United States)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

    The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

  7. Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes

    OpenAIRE

    Barbagallo, Ignazio; Vanella, Luca; Cambria, Maria T.; Tibullo, Daniele; Godos, Justyna; Guarnaccia, Laura; Zappalà, Agata; Galvano, Fabio; Li Volti, Giovanni

    2016-01-01

    Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti-neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 μM) treatment, either at the beginning or at the end of adipogenic differentiati...

  8. Roles of phosphatidate phosphatase enzymes in lipid metabolism

    OpenAIRE

    Carman, George M.; Han, Gil-Soo

    2006-01-01

    Phosphatidate phosphatase (PAP) enzymes catalyze the dephosphorylation of phosphatidate, yielding diacylglycerol and inorganic phosphate. In eukaryotic cells, PAP activity has a central role in the synthesis of phospholipids and triacylglycerol through its product diacylglycerol, and it also generates and/or degrades lipid-signaling molecules that are related to phosphatidate. There are two types of PAP enzyme, Mg2+ dependent (PAP1) and Mg2+ independent (PAP2), but only genes encoding PAP2 en...

  9. Conservation of lipid metabolic gene transcriptional regulatory networks in fish and mammals.

    Science.gov (United States)

    Carmona-Antoñanzas, Greta; Tocher, Douglas R; Martinez-Rubio, Laura; Leaver, Michael J

    2014-01-15

    Lipid content and composition in aquafeeds have changed rapidly as a result of the recent drive to replace ecologically limited marine ingredients, fishmeal and fish oil (FO). Terrestrial plant products are the most economic and sustainable alternative; however, plant meals and oils are devoid of physiologically important cholesterol and long-chain polyunsaturated fatty acids (LC-PUFA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acids. Although replacement of dietary FO with vegetable oil (VO) has little effect on growth in Atlantic salmon (Salmo salar), several studies have shown major effects on the activity and expression of genes involved in lipid homeostasis. In vertebrates, sterols and LC-PUFA play crucial roles in lipid metabolism by direct interaction with lipid-sensing transcription factors (TFs) and consequent regulation of target genes. The primary aim of the present study was to elucidate the role of key TFs in the transcriptional regulation of lipid metabolism in fish by transfection and overexpression of TFs. The results show that the expression of genes of LC-PUFA biosynthesis (elovl and fads2) and cholesterol metabolism (abca1) are regulated by Lxr and Srebp TFs in salmon, indicating highly conserved regulatory mechanism across vertebrates. In addition, srebp1 and srebp2 mRNA respond to replacement of dietary FO with VO. Thus, Atlantic salmon adjust lipid metabolism in response to dietary lipid composition through the transcriptional regulation of gene expression. It may be possible to further increase efficient and effective use of sustainable alternatives to marine products in aquaculture by considering these important molecular interactions when formulating diets. PMID:24177230

  10. Gastrodia elata Ameliorates High-Fructose Diet-Induced Lipid Metabolism and Endothelial Dysfunction

    OpenAIRE

    Min Chul Kho; Yun Jung Lee; Jeong Dan Cha; Kyung Min Choi; Dae Gill Kang; Ho Sub Lee

    2014-01-01

    Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB) attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF) diet animal model. Rats were fed the 65% HF diet with/...

  11. Ractopamine effect on lipid metabolism and GLUT4 amount of finishing pigs

    OpenAIRE

    ARAUJO, Thiago Santos; PORTO, Laura Cristina JARDIM; MARIO, Erica GUILHEN; PEREIRA, Luciano Jose; FERREIRA, Matheus Soares DA SILVA; ZANGERONIMO, Marcio Gilberto; NAPIMOGA, MARCELO HENRIQUE; BOTION, Leida Maria; SOUSA, Raimundo Vicente DE

    2014-01-01

    Ractopamine (RAC) causes fat deposition and/or fatty acid synthesis reduction and increases the rate of protein synthesis and muscle growth. However, there are few scientific studies detailing the mechanism of action of RAC and its possible metabolic pathways in swine. The objective of this study was to evaluate the effect of RAC on lipid metabolism of finishing pigs. Subcutaneous and retroperitoneal fat, muscle, and blood samples were collected at slaughter. Forty pigs were fed different RAC...

  12. Significantly fewer protein functional changing variants for lipid metabolism in Africans than in Europeans

    OpenAIRE

    Xue, Cheng; Liu, Xiaoming; Gong, Yun; Zhao, Yuhai; Fu, Yun-Xin

    2013-01-01

    Background The disorders in metabolism of energy substances are usually related to some diseases, such as obesity, diabetes and cancer, etc. However, the genetic background for these disorders has not been well understood. In this study, we explored the genetic risk differences among human populations in metabolism (catabolism and biosynthesis) of energy substances, including lipids, carbohydrates and amino acids. Results Two genotype datasets (Hapmap and 1000 Genome) were used for this study...

  13. Lipid metabolism disorders and bone dysfunction-interrelated and mutually regulated (Review)

    OpenAIRE

    Tian, Li; Yu, Xijie

    2015-01-01

    The association between lipid and bone metabolism has become an increasing focus of interest in recent years, and accumulating evidence has shown that atherosclerosis (AS) and osteoporosis (OP), a disorder of bone metabolism, frequently co-exist. Fat and bone are known to share a common progenitor cell: Multipotent mesenchymal stem cells (MSC) in the bone marrow (BM), which are able to differentiate into various cell phenotypes, including osteoblasts, adipocytes and chondrocytes. Laboratory-b...

  14. Effect of Centella asiatica on Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

    OpenAIRE

    Yun Zhao; Ping Shu; Youzhi Zhang; Limin Lin; Haihong Zhou; Zhentian Xu; Daqin Suo; Anzhi Xie; Xin Jin

    2014-01-01

    Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) of Centella asiatica had a...

  15. Alterations of metabolic activity in human osteoarthritic osteoblasts by lipid peroxidation end product 4-hydroxynonenal

    OpenAIRE

    Shi, Qin; Vaillancourt, France; Côté, Véronique; Fahmi, Hassan; Lavigne, Patrick; Afif, Hassan; Di Battista, John A.; Fernandes, Julio C; Benderdour, Mohamed

    2006-01-01

    4-Hydroxynonenal (HNE), a lipid peroxidation end product, is produced abundantly in osteoarthritic (OA) articular tissues, but its role in bone metabolism is ill-defined. In this study, we tested the hypothesis that alterations in OA osteoblast metabolism are attributed, in part, to increased levels of HNE. Our data showed that HNE/protein adduct levels were higher in OA osteoblasts compared to normal and when OA osteoblasts were treated with H2O2. Investigating osteoblast markers, we found t...

  16. Effect of hydrogen fluoride inhalation on lipid metabolism in guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Philibert, C.; Dousset, J.C.; Rioufol, C.; Bourbon, P. (Department of Toxicology, Faculte de Pharmacie, Toulouse (France))

    1991-01-01

    The action of fluoride in vivo (exposure 96 hrs to 7 mg/m3) on the metabolism of cyclic AMP and relationship between cAMP and lipid metabolism was investigated. The mean values for cAMP, non esterified fatty acids and cholesterol were significantly increased after hydrogen fluoride exposure. cAMP is directly responsible for the increased lipolysis. In animals exposed to HF, theophylline injection causes increases of non esterified fatty acids and not produces modification of cholesterol level.

  17. Role of insulin-like growth factor binding protein-3 in glucose and lipid metabolism

    OpenAIRE

    Kim, Ho-Seong

    2013-01-01

    Insulin-like growth factor binding protein (IGFBP)-3 has roles in modulating the effect of IGFs by binding to IGFs and inhibiting cell proliferation in an IGF-independent manner. Although recent studies have been reported that IGFBP-3 has also roles in metabolic regulation, their exact roles in adipose tissue are poorly understood. In this review, we summarized the studies about the biological roles in glucose and lipid metabolism. IGFBP-3 overexpression in transgenic mice suggested that IGFB...

  18. The functions of cardiolipin in cellular metabolism-potential modifiers of the Barth syndrome phenotype.

    Science.gov (United States)

    Raja, Vaishnavi; Greenberg, Miriam L

    2014-04-01

    The phospholipid cardiolipin (CL) plays a role in many cellular functions and signaling pathways both inside and outside of mitochondria. This review focuses on the role of CL in energy metabolism. Many reactions of electron transport and oxidative phosphorylation, the transport of metabolites required for these processes, and the stabilization of electron transport chain supercomplexes require CL. Recent studies indicate that CL is required for the synthesis of iron-sulfur (Fe-S) co-factors, which are essential for numerous metabolic pathways. Activation of carnitine shuttle enzymes that are required for fatty acid metabolism is CL dependent. The presence of substantial amounts of CL in the peroxisomal membrane suggests that CL may be required for peroxisomal functions. Understanding the role of CL in energy metabolism may identify physiological modifiers that exacerbate the loss of CL and underlie the variation in symptoms observed in Barth syndrome, a genetic disorder of CL metabolism. PMID:24445246

  19. Daily rhythms in expression of genes of hepatic lipid metabolism in Atlantic salmon (Salmo salar L..

    Directory of Open Access Journals (Sweden)

    Mónica B Betancor

    Full Text Available In mammals, several genes involved in liver lipid and cholesterol homeostasis are rhythmically expressed with expression shown to be regulated by clock genes via Rev-erb 1α. In order to elucidate clock gene regulation of genes involved in lipid metabolism in Atlantic salmon (Salmo salar L., the orphan nuclear receptor Rev-erb 1α was cloned and 24 h expression of clock genes, transcription factors and genes involved in cholesterol and lipid metabolism determined in liver of parr acclimated to a long-day photoperiod, which was previously shown to elicit rhythmic clock gene expression in the brain. Of the 31 genes analysed, significant daily expression was demonstrated in the clock gene Bmal1, transcription factor genes Srebp1, Lxr, Pparα and Pparγ, and several lipid metabolism genes Hmgcr, Ipi, ApoCII and El. The possible regulatory mechanisms and pathways, and the functional significance of these patterns of expression were discussed. Importantly and in contrast to mammals, Per1, Per2, Fas, Srebp2, Cyp71α and Rev-erb 1α did not display significant daily rhythmicity in salmon. The present study is the first report characterising 24 h profiles of gene expression in liver of Atlantic salmon. However, more importantly, the predominant role of lipids in the nutrition and metabolism of fish, and of feed efficiency in determining farming economics, means that daily rhythmicity in the regulation of lipid metabolism will be an area of considerable interest for future research in commercially important species.

  20. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Ji P

    2016-03-01

    Full Text Available Peng Ji, Tong Yu, Ying Liu, Jie Jiang, Jie Xu, Ying Zhao, Yanna Hao, Yang Qiu, Wenming Zhao, Chao WuCollege of Pharmacy, Liaoning Medical University, Jinzhou, Liaoning Province, People’s Republic of ChinaAbstract: Naringenin (NRG, a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only ~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle

  1. Lipidomics reveals control of Mycobacterium tuberculosis virulence lipids via metabolic coupling.

    Science.gov (United States)

    Jain, Madhulika; Petzold, Christopher J; Schelle, Michael W; Leavell, Michael D; Mougous, Joseph D; Bertozzi, Carolyn R; Leary, Julie A; Cox, Jeffery S

    2007-03-20

    Mycobacterium tuberculosis synthesizes specific polyketide lipids that interact with the host and are required for virulence. Using a mass spectrometric approach to simultaneously monitor hundreds of lipids, we discovered that the size and abundance of two lipid virulence factors, phthiocerol dimycocerosate (PDIM) and sulfolipid-1 (SL-1), are controlled by the availability of a common precursor, methyl malonyl CoA (MMCoA). Consistent with this view, increased levels of MMCoA led to increased abundance and mass of both PDIM and SL-1. Furthermore, perturbation of MMCoA metabolism attenuated pathogen replication in mice. Importantly, we detected increased PDIM synthesis in bacteria growing within host tissues and in bacteria grown in culture on odd-chain fatty acids. Because M. tuberculosis catabolizes host lipids to grow during infection, we propose that growth of M. tuberculosis on fatty acids in vivo leads to increased flux of MMCoA through lipid biosynthetic pathways, resulting in increased virulence lipid synthesis. Our results suggest that the shift to host lipid catabolism during infection allows for increased virulence lipid anabolism by the bacterium. PMID:17360366

  2. Lipid metabolism and body composition in Gclm(−/−) mice

    International Nuclear Information System (INIS)

    In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate–cysteine ligase modifier subunit gene (Gclm(−/−)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(−/−) mice and littermate wild-type (WT) controls received a normal diet or an HFD for 11 weeks. HFD-fed Gclm(−/−) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(−/−) mice, feeding these mice an HFD did not produce excess body weight nor fat storage. Gclm(−/−) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(−/−) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(−/−) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(−/−) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis. -- Highlights: ► A high fat diet does not produce body weight and fat gain in Gclm(−/−) mice. ► A high fat diet does not induce steatosis or insulin resistance in Gclm(−/−) mice. ► Gclm(−/−) mice have high basal metabolism and mitochondrial oxygen consumption.

  3. Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice

    Directory of Open Access Journals (Sweden)

    Yuan-Fu Lu

    2014-11-01

    Full Text Available Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2 were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1 and FA synthetase (Fasn were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.

  4. Sex Hormones Affect Aging Process by Influencing Lipid Profiles,Cellular Immunological Function and Lipid Peroxides and Oxidation System

    Institute of Scientific and Technical Information of China (English)

    吴赛珠; 谭家余; 周忠江; 周可祥; 容志毅

    2003-01-01

    .136、0.532、0.379、0.394、0.234 (P<0.001); HDL - C、HDL - C/TC、HDL - C/LDL - C、CD3 + 、CD4 +/CD8 + 、SOD showed a negatively correlation with E2/T respectively, γequaled - 0.563、 - 0.332、 - 0.654、 -0.1530、-0.4140、-0.236(P<0.001). In women,the serum concentrations of FSH、 LH increased significantly after menopause; PRL increased little with aging; compared with young group, E2 and P in postmenopausal groups reduced obviously, E2/P revealed significant reduce with aging. T enhanced significantly after menopause, but nor did FT. E2, P and the ratio of E2/P were negatively correlated with age respectively by bivariate correlation analysis, and a positive relation between T and age. After 70 years old, the level of TC increased obviously, and so did that of TG after menopause; HDL decreased with aging, but LDL increased after 70, with the result that the ratios of HDL - C/TC and HDL- C/LDL- C all reduced with aging; apoA1 decreased gently after 70, but apoB increased significantly after menopause; correspondingly, the ratio of apoA1/apoB declined obviously. The concentration of GLU increased with aging. CD3 + and CD4 + didn't change until 60, but reduced after 60. Compared with the young groups, CD8 + remained unchanged, CD4 +/CD8 + reduced greatly with aging, CD4 + and CD8 + presented a negatively correlation with age respectively. The value of MDA in serum of women increased notably after 70 years old, but SOD activity already decreased significantly from 60. By partial correlation analysis (controlling BMI, FSH, LH and PRL),HDL- C、 CD4 +、 CD4 +/CD8 + showed a certain correlation with E2/P respectively; γ were 0.245、 0.157、0.154 (P<O.05); TG、 LDL、 apoB、 apoA1/ apoB、SOD presented a negatively correlation with E2/P respectively, γ were 0.452、 0.236、 0.321、 0.135、0.156、0.154、 0.426 (P<0.05). Conclusions The Disequilibrium of SH had correlations with lipid profile, cellular immunological function and lipid

  5. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    International Nuclear Information System (INIS)

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes

  6. Effect of oral arginine supplementation on GH secretion and lipid metabolism in Wistar trained rats

    Directory of Open Access Journals (Sweden)

    E. Luciano

    2009-01-01

    Full Text Available The Oral Arginine Supplementation (OAS and exercise are able to modify the secretion of the Growth Hormone (GH that stimulates the lipid metabolism. The aim of the study was to verify the effect of the OAS, the aerobic exercise and the combination of the OAS with the aerobic exercise on the GH secretion and lipid metabolism in rats. The sample was composted for 40 male wistar rats, divided in four groups: Sedentary control (SC, sedentary arginine (SA, trained control (TC and trained arginine (TA. The AS and AT received the oral supplementation in alternated days and the groups CT and AT realized swimming exercise for 1hour/day with overload equivalent to 5% of body mass five days per week during 4 weeks. The concentrations of GH were significantly difference between the sedentary groups (SC and AS and (TC and AT and the lipid metabolism did not change throughout all groups. In conclusions, aerobic physical training did not modify the lipid metabolism and diminishes the values of GH concentration and the OAS did not modify the concentration of GH in Wistar rats.

  7. Overexpression of Jazf1 reduces body weight gain and regulates lipid metabolism in high fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Woo Young; Bae, Ki Beom; Kim, Sung Hyun; Yu, Dong Hun; Kim, Hei Jung; Ji, Young Rae; Park, Seo Jin; Park, Si Jun; Kang, Min-Cheol; Jeong, Ja In [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Park, Sang-Joon [College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Sang Gyu [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of); Lee, Inkyu [School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842 (Korea, Republic of); Kim, Myoung Ok [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Yoon, Duhak, E-mail: dhyoon@knu.ac.kr [School of Animal BT Sciences, Sangju Campus, Kyungpook National University, 386 Gajang-dong, Sangju, Gyeongsangbuk-do 742-211 (Korea, Republic of); Ryoo, Zae Young, E-mail: jaewoong64@hanmail.net [School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701 (Korea, Republic of)

    2014-02-14

    Highlights: • The expression of Jazf1 in the liver suppressed lipid accumulation. • Jazf1 significantly increases transcription of fatty acid synthase. • Jazf1 plays a critical role in the regulation of energy and lipid homeostasis. • Jazf1 associates the development of metabolic disorder. • Jazf1 may provide a new therapeutic target in the management of metabolic disorder. - Abstract: Jazf1 is a 27 kDa nuclear protein containing three putative zinc finger motifs that is associated with diabetes mellitus and prostate cancer; however, little is known about the role that this gene plays in regulation of metabolism. Recent evidence indicates that Jazf1 transcription factors bind to the nuclear orphan receptor TR4. This receptor regulates PEPCK, the key enzyme involved in gluconeogenesis. To elucidate Jazf1’s role in metabolism, we fed a 60% fat diet for up to 15 weeks. In Jazf1 overexpression mice, weight gain was found to be significantly decreased. The expression of Jazf1 in the liver also suppressed lipid accumulation and decreased droplet size. These results suggest that Jazf1 plays a critical role in the regulation of lipid homeostasis. Finally, Jazf1 may provide a new therapeutic target in the management of obesity and diabetes.

  8. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan; Fenger, Mogens

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI R...... five polymorphisms was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting for...

  9. Lipid metabolism in employees of the Poles'e state radiation-ecological reserve

    International Nuclear Information System (INIS)

    The results of the investigation show significant deviation in indexes of lipid metabolism typical for Chernobyl liquidators and employees of the reserve, living on territories with density of 137Cs contamination exceeding 15 Ci/km2 thus they are at a higher risk of atherosclerosis

  10. Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice

    Science.gov (United States)

    HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R (Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor ...

  11. Lipid Metabolism, Compartmentalization and Signalling in the Regulation of Pollen Tube Growth

    Czech Academy of Sciences Publication Activity Database

    Žárský, Viktor; Potocký, Martin; Baluška, F.; Cvrčková, F.

    Volume 3. Heidelberg: Springer Verlag, 2006 - (Malho, R.), s. 117-138. (Plant Cell Monographs). ISBN 3-540-31121-1 R&D Projects: GA AV ČR IAA6038410; GA ČR GA204/05/0268 Institutional research plan: CEZ:AV0Z50380511 Keywords : Pollen Tube Growth * Lipid Metabolism * Compartmentalization Subject RIV: EB - Genetics ; Molecular Biology

  12. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  13. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Science.gov (United States)

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  14. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

  15. The Assessment of Relation Between Lipids Metabolism Disorder and Periodontal Diseases in Cardiovascular Patients

    Directory of Open Access Journals (Sweden)

    AK.Khoshkhoo Nejad

    2005-02-01

    Full Text Available Statement of Problem: There are many risk factor for periodontal diseases and from this point the disorders of lipid metabolism also may be a risk factor for pcriodononlal diseases.Purpose: The purpose of this study was to evaluate the relation of periodontal disease and disorder of lipids metabolism in cardio vascular patients.Materials and Methods: In this sectional study, 45 patients who were hospitalized in shahid rajaee hospital divided and studied in two group, (included test group with 27 patents and control group with 18 patient. In both group the level of serum lipids including triglycerid, total cholesterol and LDL cholesterol were determined and periodontal status were estimated by CPITN index. Then statistical result processed by Mann-Whiney U test and spearman- correlation.Results: The results showed thai CPITN index in high lipid group was more than low lipid group and spearman correlation between triglycerid and CPITN was 0.2S3 between cholesterol and CPITN was 0.372 and between LDL and CPITN was 0.230.Conclusion: In this study we found that there is a specific and significant relation between periodontal disease and serum lipids in cardio vascular patients.

  16. Lipid signaling in adipose tissue: Connecting inflammation & metabolism

    Czech Academy of Sciences Publication Activity Database

    Masoodi, M.; Kuda, Ondřej; Rossmeisl, Martin; Flachs, Pavel; Kopecký, Jan

    2015-01-01

    Roč. 1851, č. 4 (2015), s. 503-518. ISSN 1388-1981 R&D Projects: GA ČR(CZ) GA13-00871S; GA MŠk(CZ) 7E12073; GA MŠk(CZ) LH14040 Institutional support: RVO:67985823 Keywords : adipocyte * futile substrate cycle * macrophage Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.162, year: 2014

  17. Alterations in Lipid and Inositol Metabolisms in Two Dopaminergic Disorders.

    Directory of Open Access Journals (Sweden)

    Eva C Schulte

    Full Text Available Serum metabolite profiling can be used to identify pathways involved in the pathogenesis of and potential biomarkers for a given disease. Both restless legs syndrome (RLS and Parkinson`s disease (PD represent movement disorders for which currently no blood-based biomarkers are available and whose pathogenesis has not been uncovered conclusively. We performed unbiased serum metabolite profiling in search of signature metabolic changes for both diseases.456 metabolites were quantified in serum samples of 1272 general population controls belonging to the KORA cohort, 82 PD cases and 95 RLS cases by liquid-phase chromatography and gas chromatography separation coupled with tandem mass spectrometry. Genetically determined metabotypes were calculated using genome-wide genotyping data for the 1272 general population controls.After stringent quality control, we identified decreased levels of long-chain (polyunsaturated fatty acids of individuals with PD compared to both RLS (PD vs. RLS: p = 0.0001 to 5.80x10-9 and general population controls (PD vs. KORA: p = 6.09x10-5 to 3.45x10-32. In RLS, inositol metabolites were increased specifically (RLS vs. KORA: p = 1.35x10-6 to 3.96x10-7. The impact of dopaminergic drugs was reflected in changes in the phenylalanine/tyrosine/dopamine metabolism observed in both individuals with RLS and PD.A first discovery approach using serum metabolite profiling in two dopamine-related movement disorders compared to a large general population sample identified significant alterations in the polyunsaturated fatty acid metabolism in PD and implicated the inositol metabolism in RLS. These results provide a starting point for further studies investigating new perspectives on factors involved in the pathogenesis of the two diseases as well as possible points of therapeutic intervention.

  18. FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1.

    Directory of Open Access Journals (Sweden)

    Carsten C Scholz

    2016-01-01

    Full Text Available The asparagine hydroxylase, factor inhibiting HIF (FIH, confers oxygen-dependence upon the hypoxia-inducible factor (HIF, a master regulator of the cellular adaptive response to hypoxia. Studies investigating whether asparagine hydroxylation is a general regulatory oxygen-dependent modification have identified multiple non-HIF targets for FIH. However, the functional consequences of this outside of the HIF pathway remain unclear. Here, we demonstrate that the deubiquitinase ovarian tumor domain containing ubiquitin aldehyde binding protein 1 (OTUB1 is a substrate for hydroxylation by FIH on N22. Mutation of N22 leads to a profound change in the interaction of OTUB1 with proteins important in cellular metabolism. Furthermore, in cultured cells, overexpression of N22A mutant OTUB1 impairs cellular metabolic processes when compared to wild type. Based on these data, we hypothesize that OTUB1 is a target for functional hydroxylation by FIH. Additionally, we propose that our results provide new insight into the regulation of cellular energy metabolism during hypoxic stress and the potential for targeting hydroxylases for therapeutic benefit.

  19. An evaluation of the mechanism of ABCA7 on cellular lipid release in ABCA7-HEC293 cell

    Institute of Scientific and Technical Information of China (English)

    WU Cheng-ai; WANG Na; ZHAO Dan-hui

    2013-01-01

    Background ABCA7 is a member of the ABCA subfamily that shows a high degree of homology to ABCA1 and,like ABCA1,mediates cellular cholesterol and phospholipid release by apolipoproteins when transfected in vitro.However,expression of ABCA7 has been shown to be downregulated by increased cellular cholesterol while ABCA1 was upregulated.Methods The underlying mechanism for this effect was examined in ABCA1 or ABCA7-transfected HEC293.Lipid content in the medium and cells was determined by enzymatic assays.Gene expression was quantitated by real time PCR,and protein content was determined by Western blotting.Results While ABCA7 mRNA was decreased by 25-hydroxycholesterol treatment,ABCA1 was apparently increased.Treatment with the synthetic LXR agonist T0901317 (T09) upregulated ABCA1 expression and apoAI-mediated cellular lipid release in ABCA1-transfected HEC293 cells,but ABCA7 expression and cellular lipid release in ABCA7-transfected HEC293 cells showed no obvious changes.Conclusion The ABCA7 gene is regulated by sterol in a direction opposite to that of ABCA1.

  20. Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation

    Science.gov (United States)

    Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

    2016-01-01

    Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms. PMID:27386520

  1. Relationship between resting pulse rate and lipid metabolic dysfunctions in Chinese adults living in rural areas.

    Directory of Open Access Journals (Sweden)

    Chong-jian Wang

    Full Text Available BACKGROUND: Resting pulse rate has been observed to be associated with cardiovascular diseases. However, its association with lipid metabolic dysfunctions remains unclear, especially resting pulse rate as an indicator for identifying the risk of lipid metabolic dysfunctions. The purpose of this study was to examine the association between resting pulse rate and lipid metabolic dysfunctions, and then evaluate the feasibility of resting pulse rate as an indicator for screening the risk of lipid metabolic dysfunctions. METHODS: A cross-sectional survey was performed, and 16,926 subjects were included in this study from rural community residents aged 35-78 years. Resting pulse rate and relevant covariates were collected from a standard questionnaire. The fasting blood samples were collected and measured for lipid profile. Predictive performance was analyzed by receiver operating characteristic (ROC curve. RESULTS: A significant correlation was observed between resting pulse rate and TC (r = 0.102, P = 0.001, TG (r = 0.182, P = 0.001, and dyslipidemia (r = 0.037, P = 0.008. In the multivariate models, the adjusted odds ratios for hypercholesterolemia (from 1.07 to 1.15, hypertriglyceridemia (1.11 to 1.16, low HDL hypercholesterolemia (1.03 to 1.06, high LDL hypercholesterolemia (0.92 to 1.14, and dyslipidemia (1.04 to 1.07 were positively increased across quartiles of resting pulse rate (P for trend <0.05. The ROC curve indicated that resting pulse rate had low sensitivity (78.95%, 74.18%, 51.54%, 44.39%, and 54.22%, specificity (55.88%, 59.46%, 57.27%, 65.02%, and 60.56%, and the area under ROC curve (0.70, 0.69, 0.54, 0.56, and 0.58 for identifying the risk of hypercholesterolemia, hypertriglyceridemia, low HDL hypercholesterolemia, high LDL hypercholesterolemia, and dyslipidemia, respectively. CONCLUSION: Fast resting pulse rate was associated with a moderate increased risk of lipid metabolic dysfunctions in rural adults. However, resting pulse

  2. Acute effects of ghrelin administration on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob;

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, p......CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single......-blind, placebo-controlled two-period crossover study. SETTING: The study was performed in a university clinical research laboratory. PARTICIPANTS: Eight healthy men aged 27.2 +/- 0.9 yr with a body mass index of 23.4 +/- 0.5 kg/m(2) were included in the study. INTERVENTION: Subjects received infusion of ghrelin...... the final 2 h of each infusion. RESULTS: Basal and insulin-stimulated glucose disposal decreased with ghrelin [basal: 1.9 +/- 0.1 (ghrelin) vs. 2.3 +/- 0.1 mg x kg(-1) x min(-1), P = 0.03; clamp: 3.9 +/- 0.6 (ghrelin) vs. 6.1 +/- 0.5 mg x kg(-1) x min(-1), P = 0.02], whereas endogenous glucose...

  3. Gender Differences in Musculoskeletal Lipid Metabolism as Assessed by Localized Two-Dimensional Correlation Spectroscopy

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    S. Sendhil Velan; Department of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia, U.S.A.

    2008-01-01

    Full Text Available Gender differences in lipid metabolism are poorly understood and difficult to study using conventional approaches. Magnetic resonance spectroscopy (MRS permits non-invasive investigation of lipid metabolism. We employed novel two- dimensional MRS techniques to quantify intramyocellular (IMCL and extramyocellular (EMCL lipid compartments and their degree of unsaturation in normal weight adult male and female subjects. Using muscle creatine (Cr for normalization, a statistically significant (p 0.05 increase in IMCL/Cr (7.8 ± 1.6 and EMCL/Cr (22.5 ± 3.6 for female subjects was observed (n = 8, as compared to IMCL/Cr (5.9 ± 1.7 and EMCL/Cr (18.4 ± 2.64 for male subjects. The degree of unsaturation within IMCL and EMCL was lower in female subjects, 1.3 ± 0.075 and 1.04 ± 0.06, respectively, as compared to that observed in males (n = 8, 1.5 ± 0.08 and 1.12 ± 0.03, respectively (p 0.05 male vs female for both comparisons. We conclude that certain salient gender differences in lipid metabolism can be assessed noninvasively by advanced MRS approaches.

  4. The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism*

    Science.gov (United States)

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E.; Hatch, Grant M.; Mayer, Gaétan

    2014-01-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  5. The epigenetic drug 5-azacytidine interferes with cholesterol and lipid metabolism.

    Science.gov (United States)

    Poirier, Steve; Samami, Samaneh; Mamarbachi, Maya; Demers, Annie; Chang, Ta Yuan; Vance, Dennis E; Hatch, Grant M; Mayer, Gaétan

    2014-07-01

    DNA methylation and histone acetylation inhibitors are widely used to study the role of epigenetic marks in the regulation of gene expression. In addition, several of these molecules are being tested in clinical trials or already in use in the clinic. Antimetabolites, such as the DNA-hypomethylating agent 5-azacytidine (5-AzaC), have been shown to lower malignant progression to acute myeloid leukemia and to prolong survival in patients with myelodysplastic syndromes. Here we examined the effects of DNA methylation inhibitors on the expression of lipid biosynthetic and uptake genes. Our data demonstrate that, independently of DNA methylation, 5-AzaC selectively and very potently reduces expression of key genes involved in cholesterol and lipid metabolism (e.g. PCSK9, HMGCR, and FASN) in all tested cell lines and in vivo in mouse liver. Treatment with 5-AzaC disturbed subcellular cholesterol homeostasis, thereby impeding activation of sterol regulatory element-binding proteins (key regulators of lipid metabolism). Through inhibition of UMP synthase, 5-AzaC also strongly induced expression of 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) and promoted triacylglycerol synthesis and cytosolic lipid droplet formation. Remarkably, complete reversal was obtained by the co-addition of either UMP or cytidine. Therefore, this study provides the first evidence that inhibition of the de novo pyrimidine synthesis by 5-AzaC disturbs cholesterol and lipid homeostasis, probably through the glycerolipid biosynthesis pathway, which may contribute mechanistically to its beneficial cytostatic properties. PMID:24855646

  6. Detrimental effects of fluvastatin on plasma lipid metabolism in rat breast carcinoma model

    Directory of Open Access Journals (Sweden)

    Kapinová Andrea

    2013-01-01

    Full Text Available From clinical practice, obvious positive effects of statins on plasma lipid metabolism are well known. On the other hand, there are several experimental rodent studies, where these beneficial effects were not confirmed. The effects of fluvastatin on selected serum lipid parameters in a rat model of experimental breast cancer were determined. The drug was dietary administered at two concentrations of 20 and 200 mg/kg. At the end of the study (experiment duration - 18 weeks the blood from each animal was collected and serum lipid parameters were evaluated. Fluvastatin in both treated groups significantly increased parameters of serum lipids (mostly in a dose dependent manner. Fluvastatin in both treated groups of animals significantly increased serum levels of triacylglycerols, total cholesterol, and LDL-, HDL-, VLDL-cholesterol when compared to the control group. Our results pointed out to the apparent harmful effects of fluvastatin on plasma lipid metabolism in rat mammary carcinogenesis. Based on our previous results, it seems that rats commonly used in cancer model studies are generally unresponsive to the hypocholesterolemic effects of statins.

  7. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism.

    Science.gov (United States)

    Molehin, Deborah; Dekker Nitert, Marloes; Richard, Kerry

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  8. THE COMBINED EFFECTS OF CATECHINS AND CAFFEINE ON CELLULAR PROLIFERATION AND LIPID METABOLISM IN 3T3-L1 CELLS%儿茶素和咖啡碱组合对3T3-L1细胞增殖及脂肪代谢的影响

    Institute of Scientific and Technical Information of China (English)

    郑国栋; 邱阳阳; 张清峰; 徐峰

    2013-01-01

    目的 研究对儿茶素和咖啡碱对3T3-L1细胞的增殖及脂肪代谢的影响.方法 采用四甲基偶氮唑盐比色法(MTT)检测对3T3-L1细胞增殖的影响;3T3-L1细胞诱导分化8d后,对各组细胞进行油红O染色并测定细胞内甘油三酯(TG)含量;细胞分化12d后,添加儿茶素和咖啡碱组合或同时添加去甲肾上腺素(NA)作用24h,分析各组细胞内脂肪分解.结果 儿茶素能明显抑制3T3-L1细胞的增殖;儿茶素和咖啡碱组合能明显抑制3T3-L1细胞分化后,细胞内TG的沉积,且在相同儿茶素浓度下,咖啡碱浓度越高抑制效果越明显.咖啡碱明显提高NA诱导成熟脂肪细胞脂解的能力,且呈剂量效应关系.结论 儿茶素和咖啡碱组合能够抑制脂肪细胞增殖和甘油三酯积聚,咖啡碱促进激素诱导脂肪细胞中脂肪分解.%Objective To investigate the combined effects of catechins and caffeine on cells proliferation and lipid metabolism in 3T3-L1 cells. Method MTT colorimetry was used to detect the effects of catechins and caffeine combination on the proliferation of 3T3-L1 cells. The differentiation of 3T3-L1 cells was induced for 8 d, then the adipocytes were stained by oil Red O, and the level of triglyceride (TG) was measured. The lipolytic effect of catechins and caffeine combination in presence or absence of noradrenaline (NA) for 24 h on 3T3-L1 cells was analyzed on the 12 th day after differentiation. Results Catechins significantly inhibited 3T3-L1 cells proliferation. Catechins and caffeine combination remarkably decreased TG accumulation after differentiation of 3T3-L1 cells, and the higher caffeine concentration was better when combined with the same catechins dose. Caffeine significantly improved NA-induced lipolysis in mature adipocytes. Conclusion Catechins and caffeine combination might inhibit cells proliferation and TG accumulation in 3T3-L1 cells. Caffeine promotes hormone-induced lipolysis in adipocytes.

  9. Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism

    Directory of Open Access Journals (Sweden)

    Benita L. McVicker

    2012-01-01

    Full Text Available Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs. However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38 and Fao rat hepatoma cells. An OA dose-dependent increase in triglyceride and stained lipids was identified which doubled (P<0.05 in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux. These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis.

  10. Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

    Energy Technology Data Exchange (ETDEWEB)

    McClure, Janela [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Margineantu, Daciana H. [Department of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Sweet, Ian R. [Department of Medicine (Division of Metabolism, Endocrinology, and Nutrition), University of Washington, Seattle, WA (United States); Polyak, Stephen J., E-mail: polyak@uw.edu [Department of Laboratory Medicine, University of Washington, Seattle, WA (United States); Department of Global Health, University of Washington, Seattle, WA (United States)

    2014-01-20

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases.

  11. Inhibition of HIV by Legalon-SIL is independent of its effect on cellular metabolism

    International Nuclear Information System (INIS)

    In this report, we further characterized the effects of silibinin (SbN), derived from milk thistle extract, and Legalon-SIL (SIL), a water-soluble derivative of SbN, on T cell metabolism and HIV infection. We assessed the effects of SbN and SIL on peripheral blood mononuclear cells (PBMC) and CEM-T4 cells in terms of cellular growth, ATP content, metabolism, and HIV infection. SIL and SbN caused a rapid and reversible (upon removal) decrease in cellular ATP levels, which was associated with suppression of mitochondrial respiration and glycolysis. SbN, but not SIL inhibited glucose uptake. Exposure of T cells to SIL (but not SbN or metabolic inhibitors) during virus adsorption blocked HIV infection. Thus, both SbN and SIL rapidly perturb T cell metabolism in vitro, which may account for its anti-inflammatory and anti-proliferative effects that arise with prolonged exposure of cells. However, the metabolic effects are not involved in SIL's unique ability to block HIV entry. - Highlights: • Silibinin (SbN) and Legalon-SIL (SIL) are cytoprotective mixtures of natural products. • SbN and SIL reduce T cell oxidative phosphorylation and glycolysis in vitro. • SIL but not SbN blocks entry of multiple HIV isolates into T cells in vitro. • SIL's suppression of HIV appears independent of its effects on T cell metabolism. • Metabolic effects of SIL and SbN may be relevant in inflammatory diseases

  12. A Novel Mathematical Model Describing Adaptive Cellular Drug Metabolism and Toxicity in the Chemoimmune System

    OpenAIRE

    Tóth, Attila; Brózik, Anna; Szakács, Gergely; Sarkadi, Balázs; Hegedüs, Tamás

    2015-01-01

    Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This “chemoimmune system” consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on d...

  13. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics.

    Science.gov (United States)

    Ji, Peng; Yu, Tong; Liu, Ying; Jiang, Jie; Xu, Jie; Zhao, Ying; Hao, Yanna; Qiu, Yang; Zhao, Wenming; Wu, Chao

    2016-01-01

    Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of -31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w

  14. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

    OpenAIRE

    Wen Tan; Zhangfeng Zhong; Shengpeng Wang; Zhanwei Suo; Xian Yang; Xiaodong Hu; Yitao Wang

    2015-01-01

    Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast can...

  15. Water Extract of Dolichos lablab Attenuates Hepatic Lipid Accumulation in a Cellular Nonalcoholic Fatty Liver Disease Model.

    Science.gov (United States)

    Im, A-Rang; Kim, Yun Hee; Lee, Hye Won; Song, Kwang Hoon

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD. PMID:27152979

  16. EFFECTS OF OZONE EXPOSURE ON LIPID METABOLISM IN HUMAN ALVEOLAR MACROPHAGES

    Science.gov (United States)

    Alveolar macrophages (AM) store arachidonic acid (AA) which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. ollowing release, there can be subsequent metabolism of AA into various potent, biological active m...

  17. Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism

    Science.gov (United States)

    Horniblow, Richard D.; Dowle, Miriam; Iqbal, Tariq H.; Latunde-Dada, Gladys O.; Palmer, Richard E.

    2015-01-01

    Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease. PMID:26378798

  18. Flight metabolism in Panstrongylus megistus (Hemiptera: Reduviidae: the role of carbohydrates and lipids

    Directory of Open Access Journals (Sweden)

    Lilián E Canavoso

    2003-10-01

    Full Text Available The metabolism of lipids and carbohydrates related to flight activity in Panstrongylus megistus was investigated. Insects were subjected to different times of flight under laboratory conditions and changes in total lipids, lipophorin density and carbohydrates were followed in the hemolymph. Lipids and glycogen were also assayed in fat body and flight muscle. In resting insects, hemolymph lipids averaged 3.4 mg/ml and significantly increased after 45 min of flight (8.8 mg/ml, P < 0.001. High-density lipophorin was the sole lipoprotein observed in resting animals. A second fraction with lower density corresponding to low-density lipophorin appeared in insects subjected to flight. Particles from both fractions showed significant differences in diacylglycerol content and size. In resting insects, carbohydrate levels averaged 0.52 mg/ml. They sharply declined more than twofold after 15 min of flight, being undetectable in hemolymph of insects flown for 45 min. Lipid and glycogen from fat body and flight muscle decreased significantly after 45 min of flight. Taken together, the results indicate that P. megistus uses carbohydrates during the initiation of the flight after which, switching fuel for flight from carbohydrates to lipids.

  19. Stearoyl-CoA desaturase – the lipid metabolism regulator

    Directory of Open Access Journals (Sweden)

    Mirosław Kucharski

    2014-03-01

    Full Text Available Stearoyl-CoA desaturase is an enzyme from the class of oxidoreductase, which catalyzes the formation of a fatty acid double bond between C9 and C10. It plays a key role in composition of the fatty acid profile in adipose tissue and animal products such as meat and milk. Additionally, it is an important regulator of metabolic processes in the body, and it determines the maintenance of energy homeostasis. This enzyme is encoded by an SCD gene, which, depending on the species, may exist as different isoforms. mRNA expression of stearoyl-CoA desaturase is dependent on many factors, including diet, hormones, and the activity of other genes. In previous studies, several mutations were characterized within the sequence of Δ9-desaturase, which may affect the activity of the protein in the tissues, as well as the value of breeding animals. Effects of particular mutations of the gene encoding the enzyme appears to be particularly important for diseases associated with obesity, diabetes, hypertension, heart diseases or cancer in humans. Also, it seems that using sheep as a potential animal model could be helpful in uncovering and understanding the mechanisms regulated by stearoyl-CoA desaturase.

  20. The emerging role of autophagy in peroxisome dynamics and lipid metabolism of phyllosphere microorganisms

    Directory of Open Access Journals (Sweden)

    Masahide eOku

    2014-03-01

    Full Text Available Eukaryotic microorganisms resident in the phyllosphere (above-ground, plant-surface environments undergo dynamic changes in nutrient conditions and adapt their metabolic pathways during proliferation or in the course of infection of host plants. Some of these metabolic switches are accomplished by regulation of organelle abundance. Recent studies have shown that autophagy plays a major role in reducing the organelle quantity, thereby contributing to the metabolic switch required for survival or virulence of the microorganisms in the phyllosphere. In this minireview the metabolic pathways in several phytopathogenic fungi and the non-infectious asporogenous yeast Candida boidinii, which involve lipid droplets and peroxisomes, are summarized. The physiological functions of Atg (Autophagy-related proteins in these organisms are discussed in relation to the dynamics of these two important organelles.

  1. The emerging role of autophagy in peroxisome dynamics and lipid metabolism of phyllosphere microorganisms.

    Science.gov (United States)

    Oku, Masahide; Takano, Yoshitaka; Sakai, Yasuyoshi

    2014-01-01

    Eukaryotic microorganisms resident in the phyllosphere (above-ground, plant-surface environments) undergo dynamic changes in nutrient conditions and adapt their metabolic pathways during proliferation or in the course of infection of host plants. Some of these metabolic switches are accomplished by regulation of organelle abundance. Recent studies have shown that autophagy plays a major role in reducing the organelle quantity, thereby contributing to the metabolic switch required for survival or virulence of the microorganisms in the phyllosphere. In this mini review the metabolic pathways in several phytopathogenic fungi and the non-infectious asporogenous yeast Candida boidinii, which involve lipid droplets and peroxisomes, are summarized. The physiological functions of Atg (Autophagy-related) proteins in these organisms are discussed in relation to the dynamics of these two important organelles. PMID:24653730

  2. Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism.

    Science.gov (United States)

    Nikkanen, Joni; Forsström, Saara; Euro, Liliya; Paetau, Ilse; Kohnz, Rebecca A; Wang, Liya; Chilov, Dmitri; Viinamäki, Jenni; Roivainen, Anne; Marjamäki, Päivi; Liljenbäck, Heidi; Ahola, Sofia; Buzkova, Jana; Terzioglu, Mügen; Khan, Nahid A; Pirnes-Karhu, Sini; Paetau, Anders; Lönnqvist, Tuula; Sajantila, Antti; Isohanni, Pirjo; Tyynismaa, Henna; Nomura, Daniel K; Battersby, Brendan J; Velagapudi, Vidya; Carroll, Christopher J; Suomalainen, Anu

    2016-04-12

    Mitochondrial dysfunction affects cellular energy metabolism, but less is known about the consequences for cytoplasmic biosynthetic reactions. We report that mtDNA replication disorders caused by TWINKLE mutations-mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)-remodel cellular dNTP pools in mice. MM muscle shows tissue-specific induction of the mitochondrial folate cycle, purine metabolism, and imbalanced and increased dNTP pools, consistent with progressive mtDNA mutagenesis. IOSCA-TWINKLE is predicted to hydrolyze dNTPs, consistent with low dNTP pools and mtDNA depletion in the disease. MM muscle also modifies the cytoplasmic one-carbon cycle, transsulfuration, and methylation, as well as increases glucose uptake and its utilization for de novo serine and glutathione biosynthesis. Our evidence indicates that the mitochondrial replication machinery communicates with cytoplasmic dNTP pools and that upregulation of glutathione synthesis through glucose-driven de novo serine biosynthesis contributes to the metabolic stress response. These results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy. PMID:26924217

  3. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage

    Directory of Open Access Journals (Sweden)

    Peter Belenky

    2015-11-01

    Full Text Available Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones. These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.

  4. ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

    Science.gov (United States)

    Vargas, Teodoro; Moreno-Rubio, Juan; Herranz, Jesús; Cejas, Paloma; Molina, Susana; González-Vallinas, Margarita; Mendiola, Marta; Burgos, Emilio; Aguayo, Cristina; Custodio, Ana B.; Machado, Isidro; Ramos, David; Gironella, Meritxell; Espinosa-Salinas, Isabel; Ramos, Ricardo; Martín-Hernández, Roberto; Risueño, Alberto; De Las Rivas, Javier; Reglero, Guillermo; Yaya, Ricardo; Fernández-Martos, Carlos; Aparicio, Jorge; Maurel, Joan; Feliu, Jaime; de Molina, Ana Ramírez

    2015-01-01

    Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group. PMID:25749516

  5. Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.

    Science.gov (United States)

    Yu, Dan; Ye, Xianlong; Wu, Qiang; Li, Shujie; Yang, Yongbi; He, Jinjiao; Liu, Yunye; Zhang, Xiaoyu; Yuan, Qingyan; Liu, Mingyao; Li, Deshan; Ren, Guiping

    2016-06-01

    Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization. PMID:26607153

  6. Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.

    Science.gov (United States)

    Ouimet, Mireille; Koster, Stefan; Sakowski, Erik; Ramkhelawon, Bhama; van Solingen, Coen; Oldebeken, Scott; Karunakaran, Denuja; Portal-Celhay, Cynthia; Sheedy, Frederick J; Ray, Tathagat Dutta; Cecchini, Katharine; Zamore, Philip D; Rayner, Katey J; Marcel, Yves L; Philips, Jennifer A; Moore, Kathryn J

    2016-06-01

    Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host. PMID:27089382

  7. Effects of Different Intensities of Endurance Exercise in Morning and Evening on the Lipid Metabolism Response

    Directory of Open Access Journals (Sweden)

    Hyeon-Ki Kim, Karina Ando, Hiroki Tabata, Masayuki Konishi, Masaki Takahashi, Mio Nishimaki, Mi Xiang, Shizuo Sakamoto

    2016-09-01

    Full Text Available To study the effects of different exercise intensity performed at different exercise times on lipid metabolism response during prolonged exercise. Nine young men performed endurance exercise at different exercise intensities (60%VO2max or Fatmax in the morning (9 am to 10 am or evening (5 pm to 6 pm; blood samples were collected before exercise and immediately and one and two hours after exercise completion. Expired gas was analyzed from the start of exercise until two hours after exercise completion. There were no significant changes in catecholamine (adrenaline and noradrenaline and free fatty acid levels between morning and evening trials for each endurance exercise intensity. However, the morning and evening trials both exhibited significantly higher lipid oxidation at Fatmax than that at 60%VO2max. These results suggest that exercise at Fatmax offers greater lipid oxidation than that at 60%VO2max, regardless of exercise timing.

  8. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

    Directory of Open Access Journals (Sweden)

    Guodong Zheng

    Full Text Available In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD, and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK, carnitine acyltransferase (CAT and hormone-sensitive lipase (HSL were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2 was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases.

  9. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens Juul; Dela, Flemming; Madsbad, Sten; Vaag, Allan A

    2003-01-01

    not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.......We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp...

  10. Regulatory role of leptin in glucose and lipid metabolism in skeletal muscle

    OpenAIRE

    Yasuhiko Minokoshi; Chitoku Toda; Shiki Okamoto

    2012-01-01

    Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulation of food intake, energy expenditure, and neuroendocrine function. Several lines of evidences indicate that independent of the anorexic effect, leptin regulates glucose and lipid metabolism in peripheral tissues in rodents and humans. It has been shown that leptin improves the diabetes phenotype in lipodystrophic patients and rodents. Moreover, leptin suppresses the development of severe, progressive impairment o...

  11. Influence of selenium deficiency and sulforaphane on lipid metabolism in growing rats

    OpenAIRE

    Nicole M. Blum; Mueller, Kristin; Mueller, Andreas S

    2014-01-01

    Introduction In recent years the trace element selenium (Se) was subject to a critical discussion regarding its role in lipid metabolism and diabetes. Some studies with animal models have shown positive effects of Se in the treatment of obesity, diabetes and hyperlipidemia. However, only high supranutritive selenate concentrations were effective [1, 2]. More recent studies in humans have shown that a high selenium status is associated with hyperlipidemia, including both increased cholesterol ...

  12. Perturbation in kidney lipid metabolic profiles in diabetic rats with reference to alcoholic oxidative stress

    OpenAIRE

    K. R. Shanmugam; Ramakrishna, C. H.; K Mallikarjuna; Reddy, K. Sathyavelu

    2009-01-01

    Diabetes is a major threat to global public health, and the number of diabetic patients is rapidly increasing worldwide. Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and alcoholic diseases. The aim of this study is to find out the impact of alcohol on lipid metabolic profiles in kidney tissue under streptozotocin induced diabetic condition. No study has been reported so far on the effect of alcohol on diabetic condition and also with ref...

  13. Supplemental N-3 polyunsaturated fatty acids in diet: their influence on lipid metabolism in the rat

    Czech Academy of Sciences Publication Activity Database

    Rauchová, Hana; Pavelka, Stanislav; Vokurková, Martina; Tribulová, N.; Soukup, Tomáš

    Bratislava: Slovak University of Technology, 2013, s. 140-145. ISBN 978-80-227-3959-7. [Industrial Toxicology 2013 /33./. Svit, Vysoké Tatry (SK), 19.06.2013-21.06.2013] R&D Projects: GA MŠk(CZ) 7AMB12SK158 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : lipid metabolism * n-3 polyunsaturated fatty acids * thyroid hormones Subject RIV: ED - Physiology

  14. Cardiovascular Risks Factors and their Relationship with Disorders of Carbohydrate and Lipid Metabolism

    OpenAIRE

    Lilian Leguen Gulgar; Maricel Castellanos; María de Jesús Sánchez Bouza; Mikhail Benet Rodríguez

    2014-01-01

    Background: cardiovascular disease has been the leading cause of death in Cuba, where studies on emerging cardiovascular risk factors as predictors of cardiovascular risk are scarce. Objective: to determine the association between cardiovascular risk factors and disorders of carbohydrate and lipid metabolism. Methods: a correlational study was conducted with a sample of 105 men and women selected from a total of 346 workers of the University of Medical Sciences of Cienfuegos from June 2011 th...

  15. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism

    DEFF Research Database (Denmark)

    Feng, Dan; Liu, Tao; Sun, Zheng;

    2011-01-01

    Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost whe...... hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis....

  16. Fructose modifies the hormonal response and modulates lipid metabolism in aerobic exercise after glucose supplementation

    OpenAIRE

    Fernández, Juan Marcelo; Da Silva-Grigoletto, Marzo Edir; Ruano-Ruiz, Juan; Caballero-Villarraso, Javier; Moreno-Luna, Rafael; Tunez-Fiñana, Isaac; Tasset-Cuevas, Inmaculada; Pérez-Martinez, Pablo; López-Miranda, José; Pérez-Jiménez, Francisco

    2008-01-01

    Abstract The metabolic response, when aerobic exercise is performed after the ingestion of glucose plus fructose, is unclear. To compare the hormonal and lipid responses provoked by the ingestion of glucose plus fructose in relation to glucose alone, during aerobic exercise and the recovery phase, we administered two beverages containing glucose plus fructose or glucose in a randomised crossover design, to twenty healthy, aerobically trained volunteers. After a 15-minute resting pe...

  17. Is hepatic lipid metabolism of beef cattle influenced by breed and dietary silage level?

    Science.gov (United States)

    2014-01-01

    Background In ruminants, unsaturated dietary fatty acids are biohydrogenated in the rumen and are further metabolised in various tissues, including liver, which has an important role in lipid and lipoprotein metabolism. Therefore, manipulation of muscle fatty acid composition should take into account liver metabolism. In the present study, the influence of breed and diet on liver lipid composition and gene expression was investigated in order to clarify the role of this organ in the lipid metabolism of ruminants. Forty purebred young bulls from two phylogenetically distant autochthonous cattle breeds, Alentejana and Barrosã, were assigned to two different diets (low vs. high silage) and slaughtered at 18 months of age. Liver fatty acid composition, mRNA levels of enzymes and transcription factors involved in lipid metabolism, as well as the plasma lipid profile, were assessed. Results In spite of similar plasma non-esterified fatty acids levels, liver triacylglycerols content was higher in Barrosã than in Alentejana bulls. Moreover, the fatty acid composition of liver was clearly distinct from the remaining tissues involved in fatty acid metabolism of ruminants, as shown by Principal Components Analysis. The hepatic tissue is particularly rich in α-linolenic acid and their products of desaturation and elongation. Results indicate that DGAT1, ELOVL2, FADS1 and FADS2 genes influence the fatty acid composition of the liver the most. Moreover, genes such as DGAT1 and ELOVL2 appear to be more sensitive to genetic background than to dietary manipulation, whereas genes encoding for desaturases, such as FADS1, appear to be modulated by dietary silage level. Conclusions Our results indicate that liver plays an important role in the biosynthesis of n-3 LC-PUFA. It is also suggested that dietary silage level influences the hepatic fatty acid metabolism in a breed-dependent manner, through changes in the expression of genes encoding for enzymes associated with the

  18. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

    2014-04-04

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  19. Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

    International Nuclear Information System (INIS)

    Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carrier systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of

  20. Interactions of Lipid Genetic Risk Scores with Estimates of Metabolic Health in a Danish Population

    DEFF Research Database (Denmark)

    Justesen, Johanne M; Allin, Kristine H; Sandholt, Camilla H; Borglykke, Anders; Krarup, Nikolaj Thure; Grarup, Niels; Linneberg, Allan; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf

    2015-01-01

    these susceptibility loci has not been fully elucidated. We tested if genetic risk scores (GRS) of lipid-associated SNPs associate with fasting serum lipid traits and if the effects are modulated by lifestyle factors or estimates of metabolic health. METHODS AND RESULTS: -The SNPs were genotyped in two...... cross-sectional design, we investigated if the effect of these wGRSs on lipid levels were modulated by diet, alcohol consumption, physical activity and smoking or the individual metabolic health status as estimated from BMI, waist circumference and insulin resistance assessed using HOMA-IR. All four...... lipid wGRSs associated strongly with their respective trait (from P=3.3×10(-69) to P=1.1×10(-123)). We found interactions between the triglyceride wGRS and BMI and waist circumference on fasting triglyceride levels in Inter99 and replicated these findings in Health2006 (Pinteraction=9.8×10(-5) and 2...

  1. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

    Institute of Scientific and Technical Information of China (English)

    Rong ZHOU; Ling WANG; Xing XU; Jing CHEN; Li-hong HU; Li-li CHEN; Xu SHEN

    2013-01-01

    Aim:To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro.Methods:HepG2 and C2C12 cells were used.Cell viability was determined using MTT assay.Real-time PCR was performed to measure the gene expression.Western blotting assay was applied to investigate the protein phosphorylation level.Enzymatic assay kits were used to detect the total cholesterol (TC),triglyceride (TG) and glucose contents.Results:Danthron (0.1,1,and 10 μmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC)in both HepG2 and C2C12 cells.Meanwhile,danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions,and the TC and TG levels.In addition,danthron treatment efficiently increased glucose consumption.The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C.Conclusion:Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.

  2. Genetic polymorphisms associated with lipid metabolism involved in the pathophysiology of ischemic stroke

    Directory of Open Access Journals (Sweden)

    Tamires Flauzino

    2014-12-01

    Full Text Available The stroke is a complex, multifactorial, and polygenic disorder that results from the interaction between the individual genetic components and environmental factors. Previous studies have established hypertension, smoking, diabetes mellitus, dyslipidemia, elevated body mass index, disturbances of coagulation and increasing age as predictors of stroke risk factors. The stroke is a more crippling than deadly disease that requires long-term institutionalization, as it decreases the quality of life of patients, resulting in higher costs to social and economic levels. It thus becomes increasingly important to emphasize the Preventive Medicine strategies. Dyslipidemia has been associated with pathophysiology of ischemic stroke and genetic polymorphisms that occur in the metabolic pathway, such as lipids metabolism, has been one of the hereditary factors related to ischemic stroke. The identification of the genetic component in the cause of dyslipidemia has been intensively investigated in recent years. Among the several genetic polymorphisms, the gene of the low-density lipoprotein receptor has been the object of many studies in the population worldwide. Data on lipid profile and study of polymorphisms of genes encoding structural proteins and enzymes related to lipid metabolism may reveal the prevalence of dyslipidemia in a population, enabling a targeted intervention for the control and prevention of atherosclerotic diseases such as ischemic stroke.

  3. Surface properties of lipoplexes modified with mannosylerythritol lipid-a and tween 80 and their cellular association.

    Science.gov (United States)

    Ding, Wuxiao; Hattori, Yoshiyuki; Qi, Xianrong; Kitamoto, Dai; Maitani, Yoshie

    2009-02-01

    The surface properties of cationic liposomes and lipoplexes largely determine the cellular association and gene transfection efficiency. In this study, we measured the surface properties, such as zeta potentials, surface pH and hydration levels of MHAPC- and OH-Chol-lipoplexes and their cellular association, without and with the modification of biosurfactant mannosylerythritol lipid-A (MEL-A) or Tween 80 (MHAPC=N,N-methyl hydroxyethyl aminopropane carbamoyl cholesterol; OH-Chol=cholesteryl-3beta-carboxyamindoethylene-N-hydroxyethylamine). Compared to OH-Chol-lipoplexes, the higher cellular association of MHAPC-lipoplexes correlated with the significantly higher zeta potentials, lower surface pH levels and "drier" surface, as evaluated by the generalized polarization of laurdan. Both MEL-A and Tween 80 modification of MHAPC-lipoplexes did not significantly change zeta potentials and surface pH levels, while MEL-A modification of OH-Chol-lipoplexes seriously decreased them. MEL-A hydrated the liposomal surface of MHAPC-lipoplexes but dehydrated that of OH-Chol-lipoplexes, while Tween 80 hydrated those of MHAPC- and OH-Chol-lipoplexes. In all, cationic liposomes composed of lipids with secondary and tertiary amine exhibited different surface properties and cellular associations of lipoplexes, and modification with surfactants further enlarged their difference. The strong hydration ability of Tween 80 may relate to the low cellular association of lipoplexes, while the dehydration of MEL-A-modified OH-Chol-lipoplexes seemed to compensate the negative zeta potential for the cellular association of lipoplexes. PMID:19182402

  4. Chronic Endocannabinoid System Stimulation Induces Muscle Macrophage and Lipid Accumulation in Type 2 Diabetic Mice Independently of Metabolic Endotoxaemia

    OpenAIRE

    Geurts, Lucie; Muccioli, Giulio G.; Delzenne, Nathalie M.; Cani, Patrice D.

    2013-01-01

    Aims Obesity and type 2 diabetes are characterised by low-grade inflammation, metabolic endotoxaemia (i.e., increased plasma lipopolysaccharides [LPS] levels) and altered endocannabinoid (eCB)-system tone. The aim of this study was to decipher the specific role of eCB-system stimulation or metabolic endotoxaemia in the onset of glucose intolerance, metabolic inflammation and altered lipid metabolism. Methods Mice were treated with either a cannabinoid (CB) receptor agonist (HU210) or low-dose...

  5. Chronic endocannabinoid system stimulation induces muscle macrophage and lipid accumulation in type 2 diabetic mice independently of metabolic endotoxaemia

    OpenAIRE

    Geurts, Lucie; Muccioli, Giulio; Delzenne, Nathalie M.; Cani, Patrice D.

    2013-01-01

    AIMS: Obesity and type 2 diabetes are characterised by low-grade inflammation, metabolic endotoxaemia (i.e., increased plasma lipopolysaccharides [LPS] levels) and altered endocannabinoid (eCB)-system tone. The aim of this study was to decipher the specific role of eCB-system stimulation or metabolic endotoxaemia in the onset of glucose intolerance, metabolic inflammation and altered lipid metabolism. METHODS: Mice were treated with either a cannabinoid (CB) receptor agonist (HU210) or low-do...

  6. The assembly of lipid droplets and its relation to cellular insulin sensitivity

    DEFF Research Database (Denmark)

    Boström, Pontus; Andersson, Linda; Li, Lu;

    2009-01-01

    The assembly of lipid droplets is dependent on PtdIns(4,5)P(2) that activates PLD(1) (phospholipase D(1)), which is important for the assembly process. ERK2 (extracellular-signal-regulated kinase 2) phosphorylates the motor protein dynein and sorts it to lipid droplets, allowing them to be...

  7. Effects of sildenafil on lipid profile and glycemic control in patients with type 2 diabetes mellitus and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Haedar Abdulhafith Al-biati

    2014-12-01

    Conclusion: We have provided the first evidence that sildenafil therapy improve glycemic control, lipid profile and body mass index in diabetic patients with metabolic syndrome. [Int J Basic Clin Pharmacol 2014; 3(6.000: 1048-1051

  8. Effect of Chromium Supplementation on Glucose Metabolism and Lipids: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

    Science.gov (United States)

    Objective. A systematic review of the effect of chromium supplementation on glucose metabolism and lipid levels. Research Design and Methods. Literature search conducted in MEDLINE and Commonwealth Agricultural Bureau. Eligible studies were English language randomized controlled trials of chromium ...

  9. New Features on the Environmental Regulation of Metabolism Revealed by Modeling the Cellular Proteomic Adaptations Induced by Light, Carbon, and Inorganic Nitrogen in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Gérin, Stéphanie; Leprince, Pierre; Sluse, Francis E; Franck, Fabrice; Mathy, Grégory

    2016-01-01

    Microalgae are currently emerging to be very promising organisms for the production of biofuels and high-added value compounds. Understanding the influence of environmental alterations on their metabolism is a crucial issue. Light, carbon and nitrogen availability have been reported to induce important metabolic adaptations. So far, the influence of these variables has essentially been studied while varying only one or two environmental factors at the same time. The goal of the present work was to model the cellular proteomic adaptations of the green microalga Chlamydomonas reinhardtii upon the simultaneous changes of light intensity, carbon concentrations (CO2 and acetate), and inorganic nitrogen concentrations (nitrate and ammonium) in the culture medium. Statistical design of experiments (DOE) enabled to define 32 culture conditions to be tested experimentally. Relative protein abundance was quantified by two dimensional differential in-gel electrophoresis (2D-DIGE). Additional assays for respiration, photosynthesis, and lipid and pigment concentrations were also carried out. A hierarchical clustering survey enabled to partition biological variables (proteins + assays) into eight co-regulated clusters. In most cases, the biological variables partitioned in the same cluster had already been reported to participate to common biological functions (acetate assimilation, bioenergetic processes, light harvesting, Calvin cycle, and protein metabolism). The environmental regulation within each cluster was further characterized by a series of multivariate methods including principal component analysis and multiple linear regressions. This metadata analysis enabled to highlight the existence of a clear regulatory pattern for every cluster and to mathematically simulate the effects of light, carbon, and nitrogen. The influence of these environmental variables on cellular metabolism is described in details and thoroughly discussed. This work provides an overview of the

  10. Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress

    Directory of Open Access Journals (Sweden)

    Bross Peter

    2009-05-01

    Full Text Available Abstract Background Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides. Results When fibroblast cultures were exposed to mild metabolic stress – by cultivation in galactose medium- the amount of mitochondria appeared to be maintained whereas the levels of individual proteins were altered. Proteins of respiratory chain complex I and IV were increased together with NAD+-dependent isocitrate dehydrogenase of the citric acid cycle illustrating cellular strategies to cope with altered energy metabolism. Furthermore, quantitative protein data, with a median standard error below 6%, were obtained for the following mitochondrial pathways: fatty acid oxidation, citric acid cycle, respiratory chain, antioxidant systems, amino acid metabolism, mitochondrial translation, protein quality control, mitochondrial morphology and apoptosis. Conclusion The robust analytical platform in combination with a well-defined compendium of mitochondrial proteins allowed quantification of single proteins as well as mapping of entire pathways. This enabled characterization of the interplay between metabolism and stress response in human cells exposed to mild stress.

  11. Radiolabelling studies on the lipid metabolism in the marine brown alga Dictyopteris membranacea

    International Nuclear Information System (INIS)

    The lipid metabolism of the marine brown alga D. membranacea was investigated using [2-14C]acetate, [1-14C]myristate, [1-14C]oleate and [1-14C]arachidonate as precursors. On incubation with [2-14C]acetate, 18:1 and 16:0 were the main products formed by de novo synthesis and incorporated into polar lipids. With all the exogenous substrates used, DGTA was strongly labelled and the subsequent rapid turnover of radioactivity suggested a key role for this lipid in the redistribution of acyl chains and most likely also in the biosynthesis of the eukaryotic galactolipids produced in the absence of PC. In the glycolipids a continuous accumulation of radioactivity was observed with all the substrates used. The labelling kinetics of molecular species of MGDG suggested the desaturation of 18:1 to 18:4 and of 20:4 (n-6) to 20:5 (n-3) acids on this lipid. Both PG and PE were primary acceptors of de novo synthesized fatty acids and exogenous [1-14C]oleate, but no evidence exists for a further processing of acyl chains on these lipids. TAG, although strongly labelled with all exogenous [1-14C]acids, was not labelled when [2-14C]acetate was used as a precursor indicating the flux of endogenous fatty acids to be different of that of exogenously supplied fatty acids. (author)

  12. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    Science.gov (United States)

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (Pfat formation and secretion was down-regulated (PCD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  13. Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for Intracellular Arachidonic Acid Metabolism

    Science.gov (United States)

    Toledo, Daniel A. M.; Roque, Natália R.; Teixeira, Lívia; Milán-Garcés, Erix A.; Carneiro, Alan B.; Almeida, Mariana R.; Andrade, Gustavo F. S.; Martins, Jefferson S.; Pinho, Roberto R.; Freire-de-Lima, Célio G.; Bozza, Patrícia T.; D’Avila, Heloisa

    2016-01-01

    Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as macrophages, these lipid-rich organelles are formed in response to host-pathogen interaction during infectious diseases and are sites for biosynthesis of arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear are the functions of LBs in pathogenic lower eukaryotes. In this study, we demonstrated that LBs, visualized by light microscopy with different probes and transmission electron microscopy (TEM), are produced in trypomastigote forms of the parasite Trypanosoma cruzi, the causal agent of Chagas’ disease, after both host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs from amastigotes, the intracellular forms of the parasite, growing in vivo have increased size and electron-density compared to LBs from amastigotes living in vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2 (PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated increased unsaturated lipid content and AA incorporation in stimulated parasites. Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in LBs purified from AA-stimulated parasites compared to LBs from unstimulated group. By using a specific technique for eicosanoid detection, we immunolocalized PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid storage inclusions but dynamic organelles, able to respond to host interaction and inflammatory events and involved in the AA metabolism. Acting as sources of PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of innate and adaptive immunity, newly-formed parasite LBs may be implicated with the pathogen survival in its host. PMID:27490663

  14. Effects of Insulin Treatment on Intracellular Lipid Metabolism in Liver of Diabetic Rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Lulu; WANG Yongbo; ZHOU Min; WANG Baoping

    2006-01-01

    The effects and the mechanism of insulin treatment on intracellular lipid metabolism in liver of diabetic rats were evaluated. Type 2 diabetic rats were induced by injecting the streptozotocin (25 mg/kg) and fat rich food. According to the results of oral glucose tolerance test (OGTT)and glucose-induced insulin secretion test (IRT), the rats were divided into two groups: untreated group (UT) and insulin-treated group (IT). Normal rats (NC) served as controls. The treatment with either Humulin N (4-6 U/kg every day), or saline lasted for 4 weeks. Body weight, OGTT,IRT, blood lipids, intracellular lipids in liver, hepatic fatty acid oxidation and the activity of fatty acid synthase (FAS) were detected. The change of liver histology was observed. The insulin sensitivity index (ISI) was applied to assess the status of insulin resistance. The results showed that as compared with NC group, the plasma and hepatic intracellular Triglyceride (TG), total cholesterol (TC) and free fatty acids (FFAs) were increased significantly in UT group (P<0.05), and lipid droplets could be seen dispersedly in the liver specimens, the hepatic fatty acid oxidation was increased markedly (P<0.05), while the fatty acid synthase activity decreased (P<0.05). Insulin treatment resulted in a further accumulation of lipids in liver by 55.7 %, 19.87 % and 22.2 % increase in TG, TC, FFAs respectively. The size of hepatocytes was enlarged and the cells were filled with fat drops. Plasma lipids showed little decrease and still significantly higher than those in NC group after the insulin treatment. Meanwhile, insulin treatment was companied by 20 % decrease in the rate of fatty acid oxidation and 31% increase in hepatic FAS activity compared to UT group. It was concluded that treatment with insulin on type 2 diabetic rat increases hepatic intracellular lipid accumulation by inhibiting hepatic fatty acid oxidation and activating FAS.

  15. Effects of Reductions of Body Fat and Regional Adipose Tissue on Glucose and Lipid Metabolism Among Eldery Japanese

    OpenAIRE

    Shigeto, Kazuhiro; Koyama, Hiroshi; Takemoto, Tai-ichiro

    1989-01-01

    To evaluate effects of improvement of obesity on glucose and lipid metabolism, changes of body weight, skinfolds and biochemical parameters in glucose and lipid metabolism were examined through a six month health education on excercise and diet. Subjects were 20 men and 36 women aged from 48 to 87, who had overweight and/or glucose intolerance. Weight, relative weight and fat mass were significantly reduced after the program in both sexes. Circumference ratios were reduced only in women. The ...

  16. Creatine transporter deficiency leads to increased whole body and cellular metabolism.

    Science.gov (United States)

    Perna, Marla K; Kokenge, Amanda N; Miles, Keila N; Udobi, Kenea C; Clark, Joseph F; Pyne-Geithman, Gail J; Khuchua, Zaza; Skelton, Matthew R

    2016-08-01

    Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice. PMID:27401086

  17. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T

    1997-01-01

    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  18. Relevance of liver fat to the impact of dietary extrinsic sugars on lipid metabolism.

    Science.gov (United States)

    Griffin, B A

    2015-08-01

    In contrast to the decline in mortality from many non-infectious, chronic diseases in the UK, death from liver disease has increased exponentially in men and women over the past 40 years. This is primarily because of the over consumption of alcohol, but also the increased prevalence of obesity, which is linked to early pathology through the accumulation of liver fat. Supra-physiological intakes of fructose-containing sugar can produce acute, adverse effects on lipid metabolism, and deliver excess energy that increases bodyweight and the deposition of fat in sites other than adipose tissue, including the liver. This review addresses the variable metabolic origins of liver fat, and the key importance of postprandial lipid metabolism in this respect. The effects of supra-physiological intakes of sugar are also considered in context of the real world and established threshold for the adverse effects of sugar on cardio-metabolic risk factors. The review concludes that while the average intake of sugar in the UK falls well below this critical threshold, intakes in subgroups of adults, and especially adolescents, may be cause for concern. There is also evidence to suggest that raised liver fat, acquired, in part, through an impaired removal of postprandial lipaemia, can increase sensitivity to the adverse effects of sugar at all ages. PMID:25992705

  19. Diet-gene interactions between dietary fat intake and common polymorphisms in determining lipid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Corella, D.

    2009-07-01

    Current dietary guidelines for fat intake have not taken into consideration the possible genetic differences underlying the individual variability in responsiveness to dietary components. Genetic variability has been identified in humans for all the known lipid metabolism-related genes resulting in a plethora of candidate genes and genetic variants to examine in diet-gene interaction studies focused on fat consumption. Some examples of fat-gene interaction are reviewed. These include: the interaction between total intake and the 14C/T in the hepatic lipase gene promoter in determining high-density lipoprotein cholesterol (HDL-C) metabolism; the interaction between polyunsaturated fatty acids (PUFA) and the 5G/A polymorphism in the APOA1 gene plasma HDL-C concentrations; the interaction between PUFA and the L162V polymorphism in the PPARA gene in determining triglycerides and APOC3 concentrations; and the interaction between PUFA intake and the -1131T>C in the APOA5 gene in determining triglyceride metabolism. Although hundreds of diet-gene interaction studies in lipid metabolism have been published, the level of evidence to make specific nutritional recommendations to the population is still low and more research in nutrigenetics has to be undertaken. (Author) 31 refs.

  20. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    International Nuclear Information System (INIS)

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  1. Differential effect of waterborne cadmium exposure on lipid metabolism in liver and muscle of yellow catfish Pelteobagrus fulvidraco

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Gong, Yuan [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Luo, Zhi, E-mail: luozhi99@mail.hzau.edu.cn [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China); Zheng, Jia-Lang; Zhu, Qing-Ling [Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture of P.R.C., Fishery College, Huazhong Agricultural University, Wuhan 430070 (China); Freshwater Aquaculture Collaborative Innovative Centre of Hubei Province, Wuhan 430070 (China)

    2013-10-15

    Highlights: •Cd triggered hepatic lipid accumulation through the improvement of lipogenesis. •Lipid homeostasis in muscle after Cd exposure derived from the down-regulation of both lipogenesis and lipolysis. •Our study determines the mechanism of waterborne Cd exposure on lipid metabolism in fish on a molecular level. •Our study indicates the tissue-specific regulatory effect of lipid metabolism under waterborne Cd exposure. -- Abstract: The present study was conducted to investigate the effect of waterborne cadmium (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and 0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation, the activities and expression level of several enzymes as well as the mRNA expression of transcription factors involved in lipid metabolism in liver and muscle were determined. Waterborne Cd exposure reduced growth performance, but increased Cd accumulation in liver and muscle. In liver, lipid content, the activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome proliferators-activated receptor (PPAR) α were down-regulated by Cd exposure. Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions of CPT1 and PPARγ showed no significant differences among the treatments. In muscle, lipid contents showed no significant differences among the treatments. The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARα and PPARγ were down-regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic lipid accumulation through the improvement of lipogenesis, and that lipid homeostasis in muscle was probably conducted by the down

  2. Lipid trafficking sans Vesicles: where, why, how?

    OpenAIRE

    Prinz, William A.

    2010-01-01

    Eukaryotic cells possess a remarkable diversity of lipids, which distribute among cellular membranes by well-characterized vesicle trafficking pathways. However, transport of lipids by alternate or “nonvesicular” routes is also critical for lipid synthesis, metabolism, and proper membrane partitioning. In the past few years, considerable progress has been made in characterizing the mechanisms of nonvesicular lipid transport and how it may go awry in particular diseases, but many fundamental q...

  3. Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature

    Directory of Open Access Journals (Sweden)

    María López-Malo

    2014-10-01

    Full Text Available Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 – 15°C. The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1, LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.

  4. Altered lipid metabolism in residual white adipose tissues of Bscl2 deficient mice.

    Directory of Open Access Journals (Sweden)

    Weiqin Chen

    Full Text Available Mutations in BSCL2 underlie human congenital generalized lipodystrophy type 2 disease. We previously reported that Bscl2 (-/- mice develop lipodystrophy of white adipose tissue (WAT due to unbridled lipolysis. The residual epididymal WAT (EWAT displays a browning phenotype with much smaller lipid droplets (LD and higher expression of brown adipose tissue marker proteins. Here we used targeted lipidomics and gene expression profiling to analyze lipid profiles as well as genes involved in lipid metabolism in WAT of wild-type and Bscl2(-/- mice. Analysis of total saponified fatty acids revealed that the residual EWAT of Bscl2(-/- mice contained a much higher proportion of oleic 18:1n9 acid concomitant with a lower proportion of palmitic 16:0 acid, as well as increased n3- polyunsaturated fatty acids (PUFA remodeling. The acyl chains in major species of triacylglyceride (TG and diacylglyceride (DG in the residual EWAT of Bscl2(-/- mice were also enriched with dietary fatty acids. These changes could be reflected by upregulation of several fatty acid elongases and desaturases. Meanwhile, Bscl2(-/- adipocytes from EWAT had increased gene expression in lipid uptake and TG synthesis but not de novo lipogenesis. Both mitochondria and peroxisomal β-oxidation genes were also markedly increased in Bscl2(-/- adipocytes, highlighting that these machineries were accelerated to shunt the lipolysis liberated fatty acids through uncoupling to dissipate energy. The residual subcutaneous white adipose tissue (ScWAT was not browning but displays similar changes in lipid metabolism. Overall, our data emphasize that, other than being essential for adipocyte differentiation, Bscl2 is also important in fatty acid remodeling and energy homeostasis.

  5. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

    Science.gov (United States)

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T; Binder, Elisabeth B; Bisgaard, Hans; Chatila, Talal A; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Müller-Ladner, Ulf; Neurath, Markus F; Preissner, Klaus T; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald

    2016-07-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID:27373325

  6. Evaluation of intra-cellular lipid of skeletal muscle by 1H-MR spectroscopy: in vivo and phantom study

    International Nuclear Information System (INIS)

    Objective: To elucidate the spectrum of lipid peaks in 1H-MRS of skeletal muscle and it's interpretation, to investigate the utility of 1H-MRS in evaluating intramyocellular lipid (IMCL). Methods: 1H-MRS was acquired in vivo on tibialis anterior muscle (TA) and soleus muscle (S) on 5 healthy volunteers. The spectrum of the lipid peak between 0.80 and 1.80 ppm was observed with different angle between the long axis of the calf and B0. Ex vivo phantom was an cluster of capillary tubers filled with soybean oil and fat emulsion, simulating the extramyocellular lipid (EMCL) and IMCL, respectively. The spectra of the lipid peaks were compared using different angles between the phantom and Bo field. Results: The lipid spectrum split to 3 to 4 peaks between 0.80 and 1.80 ppm on calf muscles, with 0.20 to 0.30 ppm interval between each neighbouring peak. The methylene peak of EMCL shifted to the right when the angle between long axis of the calf and B0 increased. The phantom could simulate the spectrum of 1H-MRS of the muscle, presenting two peaks with 0.20 to 0.30 ppm chemical shift difference between 0.80 and 1.80 ppm. They are methyl triglyceride and methylene, representing IMCL and EMCL, respectively. The peak splitting could be attributed to the high ordered muscle fibers and their chemical shift difference between inta-and extra-cellular distribution. The interval of IMCL and EMCL peaks attenuated when the angle between the muscle fiber and B0 increased from 0 to the magic angle (54.7 degree). Conclusion: On 1H- MRS spectrum, the peak of the EMCL and IMCL splits. This indicated that 1H-MRS is an applicable method to detect IMCL noninvasively. TA is an optimizing muscle for 1H-MRS study. (authors)

  7. Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

    Directory of Open Access Journals (Sweden)

    Lewindon PJ

    2005-07-01

    Full Text Available Abstract Background Gastroesophageal reflux disease (GORD can cause respiratory disease in children from recurrent aspiration of gastric contents. GORD can be defined in several ways and one of the most common method is presence of reflux oesophagitis. In children with GORD and respiratory disease, airway neutrophilia has been described. However, there are no prospective studies that have examined airway cellularity in children with GORD but without respiratory disease. The aims of the study were to compare (1 BAL cellularity and lipid laden macrophage index (LLMI and, (2 microbiology of BAL and gastric juices of children with GORD (G+ to those without (G-. Methods In 150 children aged Results BAL neutrophil% in G- group (n = 63 was marginally but significantly higher than that in the G+ group (n = 77, (median of 7.5 and 5 respectively, p = 0.002. Lipid laden macrophage index (LLMI, BAL percentages of lymphocyte, eosinophil and macrophage were similar between groups. Viral studies were negative in all, bacterial cultures positive in 20.7% of BALs and in 5.3% of gastric aspirates. BAL cultures did not reflect gastric aspirate cultures in all but one child. Conclusion In children without respiratory disease, GORD defined by presence of reflux oesophagitis, is not associated with BAL cellular profile or LLMI abnormality. Abnormal microbiology of the airways, when present, is not related to reflux oesophagitis and does not reflect that of gastric juices.

  8. Lipids changes in liver cancer

    Institute of Scientific and Technical Information of China (English)

    JIANG Jing-ting; XU Ning; ZHANG Xiao-ying; WU Chang-ping

    2007-01-01

    Liver is one of the most important organs in energy metabolism.Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver.It depends on the integrity of liver cellular function,which ensures homeostasis of lipid and lipoprotein metabolism.When liver cancer occurs,these processes are impaired and the plasma lipid and lipoprotein patterns may be changed.Liver cancer is the fifth common malignant tumor worldwide,and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV).HBV and HCV infections are quite common in China and other Southeast Asian countries.In addition,liver cancer is often followed by a procession of chronic hepatitis or cirrhosis,so that hepatic function is damaged obviously on these bases,which may significantly influence lipid and lipoprotein metabolism in vivo.In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.

  9. The action of D-dopachrome tautomerase as an adipokine in adipocyte lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Takeo Iwata

    Full Text Available Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiation-dependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormone-sensitive lipase (HSL and acetyl-CoA carboxylase (ACC, in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT, suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA, which phosphorylates HSL to promote its activity, were observed. These results suggested that DDT acts on adipocytes to regulate lipid metabolism through

  10. Influence of a subinhibitory dose of antifungal fatty acids from Sporothrix flocculosa on cellular lipid composition in fungi.

    Science.gov (United States)

    Benyagoub, M; Willemot, C; Bélanger, R R

    1996-10-01

    Antifungal fatty acids produced by the biocontrol fungus Sporothrix flocculosa were studied on the basis of their effect on growth and cellular lipid composition of three fungi, Cladosporium cucumerinum, Fusarium oxysporum, and S. flocculosa, whose growth was decreased by 51, 33, and 5%, respectively, when exposed to 0.4 mg fatty acid per ml. The sensitivity to fatty acid antibiotics from S. flocculosa was related to a high degree of unsaturation of phospholipid fatty acids and a low proportion of sterols. The major responses of sensitive fungi to sublethal doses of antifungal fatty acids from liquid culture of S. flocculosa were: (i) a decrease in total lipid; (ii) an increase in the degree of fatty acid unsaturation (18:1 > 18:2 > 18:3); (iii) an increase in free fatty acids and phosphatidic acid and a decrease in total phospholipids; and (iv) an increase in sterol/phospholipid ratio. These modifications in lipid composition led to an increase in membrane fluidity in sensitive fungi as demonstrated by assessment of fluoresence anisotropy using liposomes and 1,6-diphenyl-1,3,5-hexatriene probe. This alteration in the physical state of lipids appears to be responsible for the previously demonstrated alteration of membrane structure and function in fungi confronted to S. flocculosa. PMID:8898307

  11. Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism.

    Science.gov (United States)

    Masri, Selma; Rigor, Paul; Cervantes, Marlene; Ceglia, Nicholas; Sebastian, Carlos; Xiao, Cuiying; Roqueta-Rivera, Manuel; Deng, Chuxia; Osborne, Timothy F; Mostoslavsky, Raul; Baldi, Pierre; Sassone-Corsi, Paolo

    2014-07-31

    Circadian rhythms are intimately linked to cellular metabolism. Specifically, the NAD(+)-dependent deacetylase SIRT1, the founding member of the sirtuin family, contributes to clock function. Whereas SIRT1 exhibits diversity in deacetylation targets and subcellular localization, SIRT6 is the only constitutively chromatin-associated sirtuin and is prominently present at transcriptionally active genomic loci. Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity and therefore define distinctly partitioned classes of circadian genes. SIRT6 interacts with CLOCK:BMAL1 and, differently from SIRT1, governs their chromatin recruitment to circadian gene promoters. Moreover, SIRT6 controls circadian chromatin recruitment of SREBP-1, resulting in the cyclic regulation of genes implicated in fatty acid and cholesterol metabolism. This mechanism parallels a phenotypic disruption in fatty acid metabolism in SIRT6 null mice as revealed by circadian metabolome analyses. Thus, genomic partitioning by two independent sirtuins contributes to differential control of circadian metabolism. PMID:25083875

  12. Molecular Biology, Biochemistry and Cellular Physiology of Cysteine Metabolism in Arabidopsis thaliana

    Science.gov (United States)

    Hell, Rüdiger; Wirtz, Markus

    2011-01-01

    Cysteine is one of the most versatile molecules in biology, taking over such different functions as catalysis, structure, regulation and electron transport during evolution. Research on Arabidopsis has contributed decisively to the understanding of cysteine synthesis and its role in the assimilatory pathways of S, N and C in plants. The multimeric cysteine synthase complex is present in the cytosol, plastids and mitochondria and forms the centre of a unique metabolic sensing and signaling system. Its association is reversible, rendering the first enzyme of cysteine synthesis active and the second one inactive, and vice-versa. Complex formation is triggered by the reaction intermediates of cysteine synthesis in response to supply and demand and gives rise to regulation of genes of sulfur metabolism to adjust cellular sulfur homeostasis. Combinations of biochemistry, forward and reverse genetics, structural- and cell-biology approaches using Arabidopsis have revealed new enzyme functions and the unique pattern of spatial distribution of cysteine metabolism in plant cells. These findings place the synthesis of cysteine in the centre of the network of primary metabolism. PMID:22303278

  13. Effects of ozone exposure on lipid metabolism in human alveolar macrophages.

    OpenAIRE

    Friedman, M.; Madden, M C; Samet, J M; Koren, H S

    1992-01-01

    Alveolar macrophages (AM) store arachidonic acid (AA), which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. After release, there can be subsequent metabolism of AA into various potent, biologically active mediators including prostaglandins and platelet-activating factor (PAF). To examine the possibility that these mediators may account for some of the pathophysiologic alterations seen in the lung after ozone (O3) exposu...

  14. [Effect of chronic social stress on lipid metabolism in golden Syrian hamsters].

    Science.gov (United States)

    Zahaĭko, A L; Voronina, L M; Kaliman, P A; Strel'chenko, K V

    2008-01-01

    The changes of total lipids, lipoproteins and their fractions, free fatty acids, triacylglyceroles, free and esterified cholesterol levels and parameters of its metabolism in the blood serum and liver, glucose-6-phosphate dehydrogenase and lysosomal lipase activity in the liver, and also post-heparin lipases activity in blood of hamsters with chronic social stress are investigated. Is has been shown, that in stressed animals the prevalence in early terms of chronic stress lipolysis above lipogenesis is observed. In later terms of chronic stress the lipogenesis activation is also observed which, alongside with active lipolysis, can cause hyperlipidemia in blood. The latter phenomenon is obviously more characteristic of males, while in females the main source of fatty acids in blood is probably lipolysis in the liver. Proatherogenic redistribution of lipoprotein fractions, which was observed at chronic stress, becomes complicated by changes of their transformations processes under blood lipases action, in particular, lipases disbalance: by increasing of hepatic lipase activity without lipoprotein lipase activity increase. The increase of CETP activity in HDL, which is observed at stress, can be accompanied by atherogenic LDLB accumulation in the blood plasma. The chronic social stress is proatherogenic owing to lipid and lipoprotein metabolism changes, which lead to the shift of balance during lipids transport and their use by tissues. PMID:19140458

  15. Effect of dietary phosphorus levels on meat quality and lipid metabolism in broiler chickens.

    Science.gov (United States)

    Li, Xue-Ke; Wang, Jin-Zhi; Wang, Chun-Qing; Zhang, Chun-Hui; Li, Xia; Tang, Chun-Hong; Wei, Xiu-Li

    2016-08-15

    To analyze the influence of dietary phosphorus (P) levels on meat quality and lipid metabolism, a 42-day feeding experiment (P deficient group; normal group; high P level groups of H1 and H2, respectively) using 100 one-day-old broilers was conducted. Results demonstrated that the quality of broiler chicken meat in deficient or high P groups decreased relative to the normal group. High P diets resulted in increased lightness, redness values, shear forces and decreased fatty acid contents and intramuscular fat content in breast meat (p<0.01). Compared with normal group, lower malic enzyme activity, higher fatty acid synthase and AMP-activated protein kinase activities were observed in the treatment groups (p<0.05). Chickens fed with normal diets had the lowest serum total cholesterol and triglyceride levels which differed from that of other treatments (p<0.05). High-P diets significantly decreased the lipid accumulation in the liver (p<0.01), whereas phosphorus levels in breast meat increased significantly (p<0.01). It can be concluded that deficient or higher P levels could affect meat quality and expression of indicators on lipid metabolism of broiler chickens. PMID:27006242

  16. Cellular Metabolic Activity and the Oxygen and Hydrogen Stable Isotope Composition of Intracellular Water and Metabolites

    Science.gov (United States)

    Kreuzer-Martin, H. W.; Hegg, E. L.

    2008-12-01

    Intracellular water is an important pool of oxygen and hydrogen atoms for biosynthesis. Intracellular water is usually assumed to be isotopically identical to extracellular water, but an unexpected experimental result caused us to question this assumption. Heme O isolated from Escherichia coli cells grown in 95% H218O contained only a fraction of the theoretical value of labeled oxygen at a position where the O atom was known to be derived from water. In fact, fewer than half of the oxygen atoms were labeled. In an effort to explain this surprising result, we developed a method to determine the isotope ratios of intracellular water in cultured cells. The results of our experiments showed that during active growth, up to 70% of the oxygen atoms and 50% of the hydrogen atoms in the intracellular water of E. coli are generated during metabolism and can be isotopically distinct from extracellular water. The fraction of isotopically distinct atoms was substantially less in stationary phase and chilled cells, consistent with our hypothesis that less metabolically-generated water would be present in cells with lower metabolic activity. Our results were consistent with and explained the result of the heme O labeling experiment. Only about 40% of the O atoms on the heme O molecule were labeled because, presumably, only about 40% of the water inside the cells was 18O water that had diffused in from the culture medium. The rest of the intracellular water contained 16O atoms derived from either nutrients or atmospheric oxygen. To test whether we could also detect metabolically-derived hydrogen atoms in cellular constituents, we isolated fatty acids from log-phase and stationary phase E. coli and determined the H isotope ratios of individual fatty acids. The results of these experiments showed that environmental water contributed more H atoms to fatty acids isolated in stationary phase than to the same fatty acids isolated from log-phase cells. Stable isotope analyses of

  17. High-Throughput Genetics Strategies for Identifying New Components of Lipid Metabolism in the Green Alga Chlamydomonas reinhardtii.

    Science.gov (United States)

    Li, Xiaobo; Jonikas, Martin C

    2016-01-01

    Microalgal lipid metabolism is of broad interest because microalgae accumulate large amounts of triacylglycerols (TAGs) that can be used for biodiesel production (Durrett et al Plant J 54(4):593-607, 2008; Hu et al Plant J 54(4):621-639, 2008). Additionally, green algae are close relatives of land plants and serve as models to understand conserved lipid metabolism pathways in the green lineage. The green alga Chlamydomonas reinhardtii (Chlamydomonas hereafter) is a powerful model organism for understanding algal lipid metabolism. Various methods have been used to screen Chlamydomonas mutants for lipid amount or composition, and for identification of the mutated loci in mutants of interest. In this chapter, we summarize the advantages and caveats for each of these methods with a focus on screens for mutants with perturbed TAG content. We also discuss technical opportunities and new tools that are becoming available for screens of mutants altered in TAG content or perturbed in other processes in Chlamydomonas. PMID:27023238

  18. Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

    Science.gov (United States)

    Younis, Sidra; Blumenberg, Miroslav; Javed, Qamar

    2016-05-01

    Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and -420C > G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age- and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment. PMID:26858108

  19. TPhP exposure disturbs carbohydrate metabolism, lipid metabolism, and the DNA damage repair system in zebrafish liver

    Science.gov (United States)

    Du, Zhongkun; Zhang, Yan; Wang, Guowei; Peng, Jianbiao; Wang, Zunyao; Gao, Shixiang

    2016-02-01

    Triphenyl phosphate is a high production volume organophosphate flame retardant that has been detected in multiple environmental media at increasing concentrations. The environmental and health risks of triphenyl phosphate have drawn attention because of the multiplex toxicity of this chemical compound. However, few studies have paid close attention to the impacts of triphenyl phosphate on liver metabolism. We investigated hepatic histopathological, metabolomic and transcriptomic responses of zebrafish after exposure to 0.050 mg/L and 0.300 mg/L triphenyl phosphate for 7 days. Metabolomic analysis revealed significant changes in the contents of glucose, UDP-glucose, lactate, succinate, fumarate, choline, acetylcarnitine, and several fatty acids. Transcriptomic analysis revealed that related pathways, such as the glycosphingolipid biosynthesis, PPAR signaling pathway and fatty acid elongation, were significantly affected. These results suggest that triphenyl phosphate exposure markedly disturbs hepatic carbohydrate and lipid metabolism in zebrafish. Moreover, DNA replication, the cell cycle, and non-homologous end-joining and base excision repair were strongly affected, thus indicating that triphenyl phosphate hinders the DNA damage repair system in zebrafish liver cells. The present study provides a systematic analysis of the triphenyl phosphate-induced toxic effects in zebrafish liver and demonstrates that low concentrations of triphenyl phosphate affect normal metabolism and cell cycle.

  20. Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain

    DEFF Research Database (Denmark)

    Koppelhus, Uffe; Shiraishi, Takehiko; Zachar, Vladimir; Pankratova, Stanislava; Nielsen, Peter E

    2008-01-01

    and therefore mechanisms that promote endosomal escape (or avoid the endosomal route) are required for improving bioavailability. A variety of auxiliary agents (chloroquine, calcium ions, or lipophilic photosensitizers) has this effect, but improved, unaided delivery would be highly advantageous in...... particular for future in vivo applications. We find that simply conjugating a lipid domain (fatty acid) to the cationic peptide (a CatLip conjugate) increases the biological effect of the corresponding PNA (CatLip) conjugates in a luciferase cellular antisense assay up to 2 orders of magnitude. The effect...... increases with increasing length of the fatty acid (C8-C16) but in parallel also results in increased cellular toxicity, with decanoic acid being optimal. Furthermore, the relative enhancement is significantly higher for Tat peptide compared to oligoarginine. Confocal microscopy and chloroquine enhancement...

  1. Altered lipid metabolism in the aging kidney identified by three layered omic analysis.

    Science.gov (United States)

    Braun, Fabian; Rinschen, Markus M; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Hoeijmakers, Jan H J; Schumacher, Björn; Dollé, Martijn E T; Müller, Roman-Ulrich; Benzing, Thomas; Schermer, Bernhard; Kurschat, Christine E

    2016-03-01

    Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID:26886165

  2. Effect of alcohol consumption on hormones involved in carbohydrate and lipid metabolism in premenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Law, J.S.; Bhathena, S.J.; Kim, Y.C.; Berlin, E.; Judd, J.T.; Reichman, M.E.; Taylor, P.R.; Schatzkin, A. (Dept. of Agriculture, Beltsville, MD (United States) NCI, Bethesda, MD (United States))

    1991-03-15

    Alcohol consumption alters carbohydrate and lipid metabolism which are in part regulated by pancreatic and adrenal hormones. The menstrual cycle per se produces changes in several peptide and steroid hormones besides the sex hormones. The authors investigated the effect of moderate alcohol consumption on plasma hormone levels in 40 premenopausal women. The subjects were fed controlled diets containing 35% of calories from fat. In a random crossover design women were given either alcohol or a soft-drink of equal caloric value for 3 menstrual cycles. Fasting blood samples were collected in the third cycle during follicular, ovulatory and luteal phases. Plasma dehydroepiandrosterone-sulphate (DHEA-S), insulin, glucagon and cortisol levels were measured by radioimmunoassay. Moderate alcohol consumption had no effect on plasma insulin and DHEA-S levels but significantly increased glucagon and cortisol levels. Menstrual cycle per se affected plasma glucagon level in that the levels were higher during follicular phase than luteal phase. Thus, changes in carbohydrate and lipid metabolism following alcohol consumption are mediated in part by alterations in hormones involved in their metabolism.

  3. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03 < p...

  4. The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2014-05-01

    Full Text Available Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesity’s impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol, regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VA’s role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided.

  5. Metabolic Discrimination of Select List Agents by Monitoring Cellular Responses in a Multianalyte Microphysiometer

    Directory of Open Access Journals (Sweden)

    John Wikswo

    2009-03-01

    Full Text Available Harnessing the potential of cells as complex biosensors promises the potential to create sensitive and selective detectors for discrimination of biodefense agents. Here we present toxin detection and suggest discrimination using cells in a multianalyte microphysiometer (MMP that is capable of simultaneously measuring flux changes in four extracellular analytes (acidification rate, glucose uptake, oxygen uptake, and lactate production in real-time. Differential short-term cellular responses were observed between botulinum neurotoxin A and ricin toxin with neuroblastoma cells, alamethicin and anthrax protective antigen with RAW macrophages, and cholera toxin, muscarine, 2,4-dinitro-phenol, and NaF with CHO cells. These results and the post exposure dynamics and metabolic recovery observed in each case suggest the usefulness of cell-based detectors to discriminate between specific analytes and classes of compounds in a complex matrix, and furthermore to make metabolic inferences on the cellular effects of the agents. This may be particularly valuable for classifying unknown toxins.

  6. A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system.

    Directory of Open Access Journals (Sweden)

    Attila Tóth

    Full Text Available Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein expression and xenobiotic exposure conditions. Our simulations suggest that multidrug ABC transporters at Phase 0 significantly facilitate the defense function of successive network members by lowering intracellular drug concentrations. The model was extended with a novel toxicity framework which opened the possibility of performing in silico cytotoxicity assays. The alterations of the in silico cytotoxicity curves show good agreement with in vitro cell killing experiments. The behavior of the simplified kinetic model suggests that it can serve as a basis for more complex models to efficiently predict xenobiotic and drug metabolism for human medical applications.

  7. Hepatic lipid metabolism changes in short-and long-term prehepatic portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Maria-Angeles Aller; Elena Vara; Cruz García; Maria-Paz Nava; Alejandra Angulo; Fernando Sánchez-Patán; Ana Calderón; Patri Vergara; Jaime Arias

    2006-01-01

    AIM:To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension.METHODS:The concentrations of free fatty acids,diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry,in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e.portal hypertensive rats) and the control rats.RESULTS:In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ±0.50 vs 4.70 ± 0.44 nCi/g protein; P < 0.01) and was associated with an increased synthesis of free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05),diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein),triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein)and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/gprotein; P < 0.01).CONCLUSION:Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides,diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.

  8. Vitamin C improves basal metabolic rate and lipid profile in alloxan-induced diabetes mellitus in rats

    Indian Academy of Sciences (India)

    D U Owu; A B Antai; K H Udofia; A O Obembe; K O Obasi; M U Eteng

    2006-12-01

    Diabetes mellitus (DM) is a multi-factorial disease which is characterized by hyperglycaemia, lipoprotein abnormalities and oxidative stress. This study evaluated effect of oral vitamin C administration on basal metabolic rate and lipid profile of alloxan-induced diabetic rats. Vitamin C was administered at 200 mg/kg body wt. by gavage for four weeks to diabetic rats after which the resting metabolic rate and plasma lipid profile was determined. The results showed that vitamin C administration significantly ( < 0.01) reduced the resting metabolic rate in diabetic rats; and also lowered plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol. These results suggest that the administration of vitamin C in this model of established diabetes mellitus might be beneficial for the restoration of basal metabolic rate and improvement of lipid profile. This may at least in part reduce the risk of cardiovascular events seen in diabetes mellitus.

  9. Effects of coumestrol on lipid and glucose metabolism as a farnesoid X receptor ligand

    International Nuclear Information System (INIS)

    In the course of an effort to identify novel agonists of the farnesoid X receptor (FXR), coumestrol was determined to be one such ligand. Reporter and in vitro coactivator interaction assays revealed that coumestrol bound and activated FXR. Treatment of Hep G2 cells with coumestrol stimulated the expression of FXR target genes, thereby regulating the expression of target genes of the liver X receptor and hepatocyte nuclear factor-4α. Through these actions, coumestrol is expected to exert beneficial effects on lipid and glucose metabolism

  10. Systematic Review of Chinese Traditional Exercise Baduanjin Modulating the Blood Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Lijuan Mei

    2012-01-01

    Full Text Available Background. Baduanjin exercise is considered to be beneficial to modulate the blood lipid metabolism. The purpose of the systematic review was to assess the potential efficacy and safety of Baduanjin exercise. Methods. MEDLINE, EMBASE, CBM, CNKI, VIP, Chinese Important Conference Papers Database, and Chinese Dissertation Database were searched for all prospective-controlled trials of Baduanjin exercise from their inception to December 31, 2011. Results. A total of 14 studies were included. Comparing with no treatment, Baduanjin exercise significantly reduced the levels of TC, TG, LDL-C in plasma, and elevated plasma HDL-C level for healthy participants, and the pooled MD (95% confidence interval, CI was −0.58 mmol/L (−0.86, −0.30 mmol/L, −0.22 mmol/L (−0.31, −0.13 mmol/L, −0.35 mmol/L (−0.54, −0.17 mmol/L, 0.13 mmol/L (0.06, 0.21 mmol/L, respectively. Baduanjin exercise also obviously decreased the levels of TG, LDL-C in plasma comparing with no treatment for patients, and the pooled MD (95% CI was −0.30 mmol/L (−0.40, −0.19 mmol/L, −0.38 mmol/L (−0.63, −0.13 mmol/L, but there was not obvious to decrease plasma TC level or elevate plasma HDL-C level in patients with the pooled MD (95%CI, −0.39 mmol/L (−1.09, 0.31 mmol/L and 0.22 mmol/L (−0.11, 0.55 mmol/L, respectively. In addition, the obvious advantage was not observed to modulate the blood lipid metabolism in comparing Baduanjin exercise with other exercises, regardless for health participants or patients. Conclusion. Studies indicated that Baduanjin exercise could significantly decrease the levels of TC, TG, LDL-C levels in plasma and elevate plasma HDL-C level for the healthy people. It also was helpful that Baduanjin exercise modulated the blood lipid metabolism for patients. Moreover, the Baduanjin exercise did not have an obvious advantage on modulating the lipid metabolism comparing with other exercises. But the

  11. Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Nehlin, Jan O; Just, Marlene; Rustan, Arild C;

    2011-01-01

    Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating that the...

  12. The model of rat lipid metabolism disorder induced by chronic stress accompanying high-fat-diet

    OpenAIRE

    Shaodong Chen; Jing Li; Haihong Zhou; Manting Lin; Yihua Liu

    2011-01-01

    Abstract Objective To develop an animal model of Lipid Metabolism Disorder, which conforms to human clinical characteristic. Methods: There were 24 male Wistar rats that were randomly divided into 3 groups with 8 rats in each. They were group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat-diet). Group A was fed with normal diet, while group B and C were fed with high-fat-diet, going on for 55 days. From the 35th day, group B and C received one time of daily chroni...

  13. 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......) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were...

  14. L-carnitine: a partner between immune response and lipid metabolism ?

    Directory of Open Access Journals (Sweden)

    Giuseppe Famularo

    1993-01-01

    Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

  15. Dynamics of uptake and metabolism of small molecules in cellular response systems.

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    Maria Werner

    Full Text Available BACKGROUND: Proper cellular function requires uptake of small molecules from the environment. In response to changes in extracellular conditions cells alter the import and utilization of small molecules. For a wide variety of small molecules the cellular response is regulated by a network motif that combines two feedback loops, one which regulates the transport and the other which regulates the subsequent metabolism. RESULTS: We analyze the dynamic behavior of two widespread but logically distinct two-loop motifs. These motifs differ in the logic of the feedback loop regulating the uptake of the small molecule. Our aim is to examine the qualitative features of the dynamics of these two classes of feedback motifs. We find that the negative feedback to transport is accompanied by overshoot in the intracellular amount of small molecules, whereas a positive feedback to transport removes overshoot by boosting the final steady state level. On the other hand, the negative feedback allows for a rapid initial response, whereas the positive feedback is slower. We also illustrate how the dynamical deficiencies of one feedback motif can be mitigated by an additional loop, while maintaining the original steady-state properties. CONCLUSIONS: Our analysis emphasizes the core of the regulation found in many motifs at the interface between the metabolic network and the environment of the cell. By simplifying the regulation into uptake and the first metabolic step, we provide a basis for elaborate studies of more realistic network structures. Particularly, this theoretical analysis predicts that FeS cluster formation plays an important role in the dynamics of iron homeostasis.

  16. Defective lipid metabolism in sickle cell anaemia subjects in vaso-occlusive crisis

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    Kehinde Sola Akinlade

    2014-01-01

    Full Text Available Background: Abnormal lipid homeostasis has been reported in sickle cell anaemia (SCA as well as in other haematological disorders. However, there is little information on the lipid profile of SCA subjects in vaso-occlusive crisis (VOC. This study determined the lipid profile of adult SCA subjects in VOC and in steady state (SSCA. Materials and Methods: Fifty-eight (58 adults with HbSS (30 in steady state and 28 in vaso-occlusive crisis and 24 age-matched healthy individuals with HbAA genotype were recruited into this study. Standard methods were used for the determination of blood pressure (BP, packed cell volume (PCV, total white blood cell count (WBC and haemoglobin phenotype. After an overnight fast, 5 ml of venous blood was obtained from each SSCA and the controls while samples were collected upon admission in the VOC group. Plasma lipid profile was determined using enzymatic method. Differences between two groups were determined using independent Student′s t-test or Man-Whitney U as appropriate. P-values less than 0.05 were considered significant. Results: Plasma total cholesterol (TC and high density lipoprotein (HDL were significantly lower while the ratio of triglyceride (TG to HDL (TG/HDL was significantly higher in SSCA compared with the controls. Low density lipoprotein (LDL and TC were significantly lower in SCA subjects in VOC compared with controls. However, TC, TG, LDL and TG/HDL were significantly lower while HDL was significantly higher in VOC compared with SSCA. Conclusion: Sickle cell anaemia subjects have defective fasting lipid metabolism which becomes pronounced with VOC.

  17. Ethanol alters cellular activation and CD14 partitioning in lipid rafts

    International Nuclear Information System (INIS)

    Alcohol consumption interferes with innate immunity. In vivo EtOH administration suppresses cytokine responses induced through Toll-like receptor 4 (TLR4) and inhibits TLR4 signaling. Actually, EtOH exhibits a generalized suppressive effect on signaling and cytokine responses induced by through most TLRs. However, the underlying mechanism remains unknown. RAW264.7 cells were treated with LPS or co-treated with EtOH or with lipid raft-disrupting drugs. TNF-α production, IRAK-1 activation, and CD14 partition were evaluated. EtOH or nystatin, a lipid raft-disrupting drug, suppressed LPS-induced production of TNF-α. The suppressive effect of EtOH on LPS-induced TNF-α production was additive with that of methyl-β-cyclodextrin (MCD), another lipid raft-disrupting drug. EtOH interfered with IRAK-1 activation, an early TLR4 intracellular signaling event. Cell fractionation analyses show that acute EtOH altered LPS-related partition of CD14, a critical component of the LPS receptor complex. These results suggest a novel mechanism of EtOH action that involves interference with lipid raft clustering induced by LPS. This membrane action of EtOH might be one of the mechanisms by which EtOH acts as a generalized suppressor for TLR signaling

  18. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D; Humphreys, S M; Frayn, K N; Powell, D; Gibbons, G F

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non...... NEFA was significantly lower than that for output of VLDL, implying depletion of hepatic TAG stores during the experiment. In the hyperinsulinemic clamp experiments, there was on average suppression of splanchnic VLDL-TAG output although between-person variability was marked. This suppression could be...... explained by a very low supply of NEFA during the clamp. We conclude that there is an integrated pattern of metabolism in splanchnic and adipose tissues in the postabsorptive and post-glucose states. Flux of NEFA from adipose tissue drives splanchnic NEFA uptake. Splanchnic VLDL-TAG secretion appears to be...

  19. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. [Emory-MED; (SBU); (TAM); (UNC); (Vanderbilt-MED); (Utah); (UCHSC)

    2014-07-11

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  20. A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jihui; Lin, Coney Pei-Chen; Pathak, Manish C.; Temple, Brenda R.S.; Nile, Aaron H.; Mousley, Carl J.; Duncan, Mara C.; Eckert, Debra M.; Leiker, Thomas J.; Ivanova, Pavlina T.; Myers, David S.; Murphy, Robert C.; Brown, H. Alex; Verdaasdonk, Jolien; Bloom, Kerry S.; Ortlund, Eric A.; Neiman, Aaron M.; Bankaitis, Vytas A. (Emory-MED); (UNCSM); (UNC); (UCHSC); (TAM); (Vanderbilt-MED); (SBU); (Utah)

    2016-07-06

    Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches.

  1. Effect of peripheral 5-HT on glucose and lipid metabolism in wether sheep.

    Directory of Open Access Journals (Sweden)

    Hitoshi Watanabe

    Full Text Available In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species.

  2. Phosphorylation of Yeast Pah1 Phosphatidate Phosphatase by Casein Kinase II Regulates Its Function in Lipid Metabolism.

    Science.gov (United States)

    Hsieh, Lu-Sheng; Su, Wen-Min; Han, Gil-Soo; Carman, George M

    2016-05-01

    Pah1 phosphatidate phosphatase in Saccharomyces cerevisiae catalyzes the penultimate step in the synthesis of triacylglycerol (i.e. the production of diacylglycerol by dephosphorylation of phosphatidate). The enzyme playing a major role in lipid metabolism is subject to phosphorylation (e.g. by Pho85-Pho80, Cdc28-cyclin B, and protein kinases A and C) and dephosphorylation (e.g. by Nem1-Spo7) that regulate its cellular location, catalytic activity, and stability/degradation. In this work, we show that Pah1 is a substrate for casein kinase II (CKII); its phosphorylation was time- and dose-dependent and was dependent on the concentrations of Pah1 (Km = 0.23 μm) and ATP (Km = 5.5 μm). By mass spectrometry, truncation analysis, site-directed mutagenesis, phosphopeptide mapping, and phosphoamino acid analysis, we identified that >90% of its phosphorylation occurs on Thr-170, Ser-250, Ser-313, Ser-705, Ser-814, and Ser-818. The CKII-phosphorylated Pah1 was a substrate for the Nem1-Spo7 protein phosphatase and was degraded by the 20S proteasome. The prephosphorylation of Pah1 by protein kinase A or protein kinase C reduced its subsequent phosphorylation by CKII. The prephosphorylation of Pah1 by CKII reduced its subsequent phosphorylation by protein kinase A but not by protein kinase C. The expression of Pah1 with combined mutations of S705D and 7A, which mimic its phosphorylation by CKII and lack of phosphorylation by Pho85-Pho80, caused an increase in triacylglycerol content and lipid droplet number in cells expressing the Nem1-Spo7 phosphatase complex. PMID:27044741

  3. Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise

    DEFF Research Database (Denmark)

    Catoire, Milène; Alex, Sheril; Paraskevopulos, Nicolas;

    2014-01-01

    Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercis...... use of plasma triglycerides as fuel for active muscles. Our data suggest that nonexercising muscle and the local regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing lipid homeostasis during exercise.......Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise......-activated receptor-δ, presumably leading to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the...

  4. The anticancer plant triterpenoid, avicin D, regulates glucocorticoid receptor signaling: implications for cellular metabolism.

    Science.gov (United States)

    Haridas, Valsala; Xu, Zhi-Xiang; Kitchen, Doug; Jiang, Anna; Michels, Peter; Gutterman, Jordan U

    2011-01-01

    Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from "ancient hopanoids," avicins bear a structural resemblance with glucocorticoids (GCs), which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex), a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR), leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use. PMID:22132201

  5. The anticancer plant triterpenoid, avicin D, regulates glucocorticoid receptor signaling: implications for cellular metabolism.

    Directory of Open Access Journals (Sweden)

    Valsala Haridas

    Full Text Available Avicins, a family of apoptotic triterpene electrophiles, are known to regulate cellular metabolism and energy homeostasis, by targeting the mitochondria. Having evolved from "ancient hopanoids," avicins bear a structural resemblance with glucocorticoids (GCs, which are the endogenous regulators of metabolism and energy balance. These structural and functional similarities prompted us to compare the mode of action of avicin D with dexamethasone (Dex, a prototypical GC. Using cold competition assay, we show that Avicin D competes with Dex for binding to the GC receptor (GR, leading to its nuclear translocation. In contrast to Dex, avicin-induced nuclear translocation of GR does not result in transcriptional activation of GC-dependent genes. Instead we observe a decrease in the expression of GC-dependent metabolic proteins such as PEPCK and FASN. However, like Dex, avicin D treatment does induce a transrepressive effect on the pro-inflammatory transcription factor NF-κB. While avicin's ability to inhibit NF-κB and its downstream targets appear to be GR-dependent, its pro-apoptotic effects were independent of GR expression. Using various deletion mutants of GR, we demonstrate the requirement of both the DNA and ligand binding domains of GR in mediating avicin D's transrepressive effects. Modeling of avicin-GR interaction revealed that avicin molecule binds only to the antagonist confirmation of GR. These findings suggest that avicin D has properties of being a selective GR modulator that separates transactivation from transrepression. Since the gene-activating properties of GR are mainly linked to its metabolic effects, and the negative interference with the activity of transcription factors to its anti-inflammatory and immune suppressive effects, the identification of such a dissociated GR ligand could have great potential for therapeutic use.

  6. The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii.

    Science.gov (United States)

    Bottova, Iveta; Sauder, Ursula; Olivieri, Vesna; Hehl, Adrian B; Sonda, Sabrina

    2010-01-01

    Up-regulation of the membrane-bound efflux pump P-glycoprotein (P-gp) is associated with the phenomenon of multidrug-resistance in pathogenic organisms, including protozoan parasites. In addition, P-gp plays a role in normal physiological processes, however our understanding of these P-gp functions remains limited. In this study we investigated the effects of the P-gp inhibitor GF120918 in Toxoplasma gondii, a model apicomplexan parasite and an important human pathogen. We found that GF120918 treatment severely inhibited parasite invasion and replication. Further analyses of the molecular mechanisms involved revealed that the P-gp inhibitor modulated parasite motility, microneme secretion and egress from the host cell, all cellular processes known to depend on Ca2+ signaling in the parasite. In support of a potential role of P-gp in Ca2+-mediated processes, immunoelectron and fluorescence microscopy showed that T. gondii P-gp was localized in acidocalcisomes, the major Ca2+ storage in the parasite, at the plasma membrane, and in the intravacuolar tubular network. In addition, metabolic labeling of extracellular parasites revealed that inhibition or down-regulation of T. gondii P-gp resulted in aberrant lipid synthesis. These results suggest a crucial role of T. gondii P-gp in essential processes of the parasite biology and further validate the potential of P-gp activity as a target for drug development. PMID:20386707

  7. The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Iveta Bottova

    Full Text Available Up-regulation of the membrane-bound efflux pump P-glycoprotein (P-gp is associated with the phenomenon of multidrug-resistance in pathogenic organisms, including protozoan parasites. In addition, P-gp plays a role in normal physiological processes, however our understanding of these P-gp functions remains limited. In this study we investigated the effects of the P-gp inhibitor GF120918 in Toxoplasma gondii, a model apicomplexan parasite and an important human pathogen. We found that GF120918 treatment severely inhibited parasite invasion and replication. Further analyses of the molecular mechanisms involved revealed that the P-gp inhibitor modulated parasite motility, microneme secretion and egress from the host cell, all cellular processes known to depend on Ca2+ signaling in the parasite. In support of a potential role of P-gp in Ca2+-mediated processes, immunoelectron and fluorescence microscopy showed that T. gondii P-gp was localized in acidocalcisomes, the major Ca2+ storage in the parasite, at the plasma membrane, and in the intravacuolar tubular network. In addition, metabolic labeling of extracellular parasites revealed that inhibition or down-regulation of T. gondii P-gp resulted in aberrant lipid synthesis. These results suggest a crucial role of T. gondii P-gp in essential processes of the parasite biology and further validate the potential of P-gp activity as a target for drug development.

  8. New avenues for regulation of lipid metabolism by thyroid hormones and analogs.

    Science.gov (United States)

    Senese, Rosalba; Lasala, Pasquale; Leanza, Cristina; de Lange, Pieter

    2014-01-01

    Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3'-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through "non-genomic" pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism. PMID:25538628

  9. New Avenues for Regulation of Lipid Metabolism by Thyroid Hormones and Analogs

    Directory of Open Access Journals (Sweden)

    Rosalba eSenese

    2014-12-01

    Full Text Available Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs. The classic, active TH, 3,5,3’-triiodo-L-thyronine (T3 acts predominantly by binding to nuclear receptors termed TH receptors (TRs, that recognize TH response elements (TREs on the DNA, and so regulate transcription. T3 also acts through non-genomic pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TR alpha. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2, that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.

  10. The mechanism of dietary cholesterol effects on lipids metabolism in rats

    Directory of Open Access Journals (Sweden)

    Wang Jing-Feng

    2010-01-01

    Full Text Available Abstract Background Cholesterol administration has been reported to influence hepatic lipid metabolism in rats. In the present study, the effect of dietary cholesterol on hepatic activity and mRNA expression of the enzymes involved in lipid metabolism were investigated. Fourteen male Wistar rats were randomly divided into 2 groups and fed 1% cholesterol or cholesterol free AIN76 diets for 4 weeks. Results The serum triglyceride and high density lipoprotein cholesterol levels were significantly decreased but the total cholesterol and non high density lipoprotein cholesterol levels were significantly increased in the cholesterol-fed rats compared with the control rats. And the concentrations of the hepatic total cholesterol and triglyceride increased about 4-fold and 20-fold separately by dietary cholesterol. The activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, fatty acid synthase, phosphatidate phophatase and carnitine palmitoyl transferase were depressed by the cholesterol feeding (40%, 70%, 50%, 15% and 25% respectively. The results of mRNA expression showed that fatty acid synthase, carnitine palmitoyl transferase 1, carnitine palmitoyl transferase 2, and HMG-CoA reductase were down-regulated (35%, 30%, 50% and 25% respectively and acyl-CoA: cholesterol acyltransferase and cholesterol 7α-hydroxylase were up regulated (1.6 and 6.5 folds in liver by the cholesterol administration. Conclusions The dietary cholesterol increased the triglyceride accumulation in liver, but did not stimulate the activity and the gene expression of hepatic enzymes related to triglyceride and fatty acid biosynthesis.

  11. Effects of oral administration of benzylamine on glucose tolerance and lipid metabolism in rats.

    Science.gov (United States)

    Bour, S; Visentin, V; Prévot, D; Daviaud, D; Saulnier-Blache, J S; Guigne, C; Valet, P; Carpéné, C

    2005-06-01

    Repeated administration of benzylamine plus vanadate have been reported to exhibit anti-hyperglycemic effects in different models of diabetic rats. Likewise oral treatment with Moringa oleifera extracts which contain the alkaloïd moringine, identical to benzylamine, has also been shown to prevent hyperglycemia in alloxan-induced diabetic rats. With these observations we tested whether prolonged oral administration of benzylamine could interact with glucose and/or lipid metabolism. Seven week old male Wistar rats were treated for seven weeks with benzylamine 2.9 g/l in drinking water and were submitted to glucose tolerance tests. A slight decrease in water consumption was observed in benzylamine-treated animals while there was no change in body and adipose tissue weights at the end of treatment. Blood glucose and plasma insulin, triacylglycerol or cholesterol levels were not modified. However, benzylamine treatment resulted in a decrease in plasma free fatty acids in both fed and fasted conditions. Benzylamine treatment improved glucose tolerance as shown by the reduction of hyperglycemic response to intra-peritoneal glucose load. Oral benzylamine treatment did not alter the response of adipocytes to insulin nor to insulin-like actions of benzylamine plus vanadate, via in vitro activation of glucose transport or inhibition of lipolysis. This work demonstrates for the first time that oral administration of benzylamine alone influences glucose and lipid metabolism. However, these results obtained in normoglycemic rats require to be confirmed in diabetic models. PMID:16180335

  12. Maternal and fetal lipid metabolism under normal and gestational diabetic conditions.

    Science.gov (United States)

    Herrera, Emilio; Desoye, Gernot

    2016-05-01

    Maternal lipids are strong determinants of fetal fat mass. Here we review the overall lipid metabolism in normal and gestational diabetes mellitus (GDM) pregnancies. During early pregnancy, the increase in maternal fat depots is facilitated by insulin, followed by increased adipose tissue breakdown and subsequent hypertriglyceridemia, mainly as a result of insulin resistance (IR) and estrogen effects. The response to diabetes is variable as a result of greater IR but decreased estrogen levels. The vast majority of fatty acids (FAs) in the maternal circulation are esterified and associated with lipoproteins. These are taken up by the placenta and hydrolyzed by lipases. The released FAs enter various metabolic routes and are released into fetal circulation. Although these determinants are modified in maternal GDM, the fetus does not seem to receive more FAs than in non-GDM pregnancies. Long-chain polyunsaturated FAs are essential for fetal development and are obtained from the mother. Mitochondrial FA oxidation occurs in fetal tissue and in placenta and contributes to energy production. Fetal fat accretion during the last weeks of gestation occurs very rapidly and is sustained not only by FAs crossing the placenta, but also by fetal lipogenesis. Fetal hyperinsulinemia in GDM mothers promotes excess accretion of adipose tissue, which gives rise to altered adipocytokine profiles. Fetal lipoproteins are low at birth, but the GDM effects are unclear. The increase in body fat in neonates of GDM women is a risk factor for obesity in early childhood and later life. PMID:26351960

  13. Effects of osthol on blood pressure and lipid metabolism in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Ogawa, Hiroshi; Sasai, Noriko; Kamisako, Toshinori; Baba, Kimiye

    2007-05-30

    Osthol, a coumarin compound, was isolated from the dried fruits of Cnidium monnieri (Umbelliferae) and the effect of dietary osthol on hypertension and lipid metabolism was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Six-week-old male SHRSP were fed the experimental diet containing 0.05% osthol by weight for 4 weeks with free access to the diet and water. Elevation of systolic blood pressure was significantly suppressed on and after 3 weeks. In addition, significant decreases in cholesterol and triglyceride contents in the liver were recognized without any significant changes in serum lipids profiles. A comparative study on hepatic mRNA expression indicated that osthol induced a significant increase in 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase mRNA expression, which may lead to decrease in hepatic cholesterol pool through inhibition of the enzyme activity. Moreover, osthol induced a significant increase in acyl-CoA oxidase mRNA expression associated with an increase in carnitine palmitoyl transferase 1a mRNA expression, which suggests the acceleration of beta-oxidation of hepatic fatty acids. This may be responsible, at least in part, for the reduction of hepatic triglyceride content in SHRSP. These beneficial effects of osthol could be useful for both prevention of atherosclerosis and suppression of hepatic lipid accumulation. PMID:17324541

  14. A Yeast Mutant Deleted of GPH1 Bears Defects in Lipid Metabolism.

    Directory of Open Access Journals (Sweden)

    Martina Gsell

    Full Text Available In a previous study we demonstrated up-regulation of the yeast GPH1 gene under conditions of phosphatidylethanolamine (PE depletion caused by deletion of the mitochondrial (M phosphatidylserine decarboxylase 1 (PSD1 (Gsell et al., 2013, PLoS One. 8(10:e77380. doi: 10.1371/journal.pone.0077380. Gph1p has originally been identified as a glycogen phosphorylase catalyzing degradation of glycogen to glucose in the stationary growth phase of the yeast. Here we show that deletion of this gene also causes decreased levels of phosphatidylcholine (PC, triacylglycerols and steryl esters. Depletion of the two non-polar lipids in a Δgph1 strain leads to lack of lipid droplets, and decrease of the PC level results in instability of the plasma membrane. In vivo labeling experiments revealed that formation of PC via both pathways of biosynthesis, the cytidine diphosphate (CDP-choline and the methylation route, is negatively affected by a Δgph1 mutation, although expression of genes involved is not down regulated. Altogether, Gph1p besides its function as a glycogen mobilizing enzyme appears to play a regulatory role in yeast lipid metabolism.

  15. Dietary Njavara rice bran oil reduces experimentally induced hypercholesterolaemia by regulating genes involved in lipid metabolism.

    Science.gov (United States)

    Chithra, Pushpan K; Sindhu, G; Shalini, V; Parvathy, Rathnam; Jayalekshmy, Ananthasankaran; Helen, Antony

    2015-04-28

    The present study was carried out to evaluate the anti-atherogenic effect of Njavara rice bran oil (NjRBO) on atherosclerosis by modulating enzymes and genes involved in lipid metabolism in rats fed a high-cholesterol diet (HCD). Adult male rats (Sprague-Dawley strain, weighing 100-120 g) were divided into three groups of nine animals each. Group I served as the control, group II were fed a HCD and group III were fed a HCD and NjRBO (100 mg/kg body weight). The study duration was 60 d. Serum and tissue lipid profile, atherogenic index, enzymes of lipid metabolism, plasma C-reactive protein levels, serum paraoxonase and arylesterase activities, thiobarbituric acid-reactive substances, gene and protein expression of paraoxonase 1 (PON1), PPARα, ATP-binding cassette transporter A1 (ABCA1), apoB and apoA1 in the liver were quantified. Total cholesterol, TAG, phospholipid, NEFA, LDL-cholesterol concentrations in the serum and liver, lipogenic enzyme activities, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and atherogenic index were significantly increased in HCD-fed rats, but they decreased after treatment with NjRBO. HDL-cholesterol level and lecithin cholesterol acyl transferase activity were increased in the NjRBO-treated group, but decreased in the HCD-fed group. The expression levels of ABCA1, apoA1, PON1 and PPARα were found to be significantly increased in NjRBO-treated group compared with the HCD-fed group; however, the expression level of apoB was found to be higher in HCD-fed group and lower in the NjRBO-treated group. These data suggest that NjRBO possesses an anti-atherogenic property by modulating lipid metabolism and up-regulating genes involved in reverse cholesterol transport and antioxidative defence mechanism through the induction of the gene expression PON1. PMID:25823019

  16. Regulation of Ras exchange factors and cellular localization of Ras activation by lipid messengers in T cells

    Directory of Open Access Journals (Sweden)

    Jesse E. Jun

    2013-09-01

    Full Text Available The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and SOS-family GEFs.Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood.One large group of biomolecules critically involved in the control of Ras-GEFs´functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.

  17. Importance of cellular lipid modulation for apoptotic and differentiation response of colon epithelial cells

    Czech Academy of Sciences Publication Activity Database

    Hofmanová, Jiřina; Vaculová, Alena; Koubková, Zuzana; Kozubík, Alois

    Brno, 2007. s. 36-37. ISBN 978-80-239-9591-6. [Analytical Cytometry IV. 23.06.2007-26.06.2007, Brno] R&D Projects: GA ČR(CZ) GA524/07/1178; GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : colon cancer * fatty acids * cell lipids Subject RIV: BO - Biophysics

  18. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

    Science.gov (United States)

    Kaur, Amandeep; Jyoti, Kiran; Rai, Shweta; Sidhu, Rupinder; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katyal, Anju; Madan, Jitender

    2016-05-01

    In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens. PMID:27056086

  19. MicroRNAs and Lipids Metabolism%MicroRNAs与脂类代谢

    Institute of Scientific and Technical Information of China (English)

    南雪梅; 王加启; 陈海燕; 胡菡

    2013-01-01

    This article overviewed the study progression of the roles of a class of non-coding RNAs termed microRNAs on lipid metabolism and the effects of fatty acids on microRNA expression. miRNAs can regulate lipid metabolism in multiple levels. miR-122, -307, -33 and so on can regulate fatty acid synthesis, fatty acid oxidation, triglyceride synthesis, cholesterol flow and lipoprotein synthesis in direct or indirect ways via the combination to their target genes. Lipids of diets, especially the essential fatty acids, can involve in the biology processes, such as cancer resistance and inflammation remission, via the regulation of miRNAs.%本文综述了miRNAs在脂类代谢调控以及脂肪酸对miRNAs影响的研究进展.miRNA能够在转录后水平参与脂类代谢的多个层面,其中miR-122、miR-370、miR33等能够通过与靶基因(Cptlα、ABCA1等)结合,直接或间接调节细胞内脂肪酸生成、脂肪酸氧化、甘油三酯合成、胆固醇流动及脂蛋白合成等多个路径.而饮食中的脂类,尤其是必需脂肪酸,能够通过对miRNAs表达的调节参与到包括癌症抵抗、炎症缓解等多个生物学进程中.

  20. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    Science.gov (United States)

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety. PMID:26987021

  1. Differential contribution of key metabolic substrates and cellular oxygen in HIF signalling

    Energy Technology Data Exchange (ETDEWEB)

    Zhdanov, Alexander V., E-mail: a.zhdanov@ucc.ie [School of Biochemistry and Cell Biology, University College Cork, Cavanagh Pharmacy Building, College Road, Cork (Ireland); Waters, Alicia H.C. [School of Biochemistry and Cell Biology, University College Cork, Cavanagh Pharmacy Building, College Road, Cork (Ireland); Golubeva, Anna V. [Alimentary Pharmabiotic Centre, University College Cork, Bioscience Institute, Western Road, Cork (Ireland); Papkovsky, Dmitri B. [School of Biochemistry and Cell Biology, University College Cork, Cavanagh Pharmacy Building, College Road, Cork (Ireland)

    2015-01-01

    Changes in availability and utilisation of O{sub 2} and metabolic substrates are common in ischemia and cancer. We examined effects of substrate deprivation on HIF signalling in PC12 cells exposed to different atmospheric O{sub 2}. Upon 2–4 h moderate hypoxia, HIF-α protein levels were dictated by the availability of glutamine and glucose, essential for deep cell deoxygenation and glycolytic ATP flux. Nuclear accumulation of HIF-1α dramatically decreased upon inhibition of glutaminolysis or glutamine deprivation. Elevation of HIF-2α levels was transcription-independent and associated with the activation of Akt and Erk1/2. Upon 2 h anoxia, HIF-2α levels strongly correlated with cellular ATP, produced exclusively via glycolysis. Without glucose, HIF signalling was suppressed, giving way to other regulators of cell adaptation to energy crisis, e.g. AMPK. Consequently, viability of cells deprived of O{sub 2} and glucose decreased upon inhibition of AMPK with dorsomorphin. The capacity of cells to accumulate HIF-2α decreased after 24 h glucose deprivation. This effect, associated with increased AMPKα phosphorylation, was sensitive to dorsomorphin. In chronically hypoxic cells, glutamine played no major role in HIF-2α accumulation, which became mainly glucose-dependent. Overall, the availability of O{sub 2} and metabolic substrates intricately regulates HIF signalling by affecting cell oxygenation, ATP levels and pathways involved in production of HIF-α. - Highlights: • Gln and Glc regulate HIF levels in hypoxic cells by maintaining low O{sub 2} and high ATP. • HIF-α levels under anoxia correlate with cellular ATP and critically depend on Glc. • Gln and Glc modulate activity of Akt, Erk and AMPK, regulating HIF production. • HIF signalling is differentially inhibited by prolonged Glc and Gln deprivation. • Unlike Glc, Gln plays no major role in HIF signalling in chronically hypoxic cells.

  2. Differential contribution of key metabolic substrates and cellular oxygen in HIF signalling

    International Nuclear Information System (INIS)

    Changes in availability and utilisation of O2 and metabolic substrates are common in ischemia and cancer. We examined effects of substrate deprivation on HIF signalling in PC12 cells exposed to different atmospheric O2. Upon 2–4 h moderate hypoxia, HIF-α protein levels were dictated by the availability of glutamine and glucose, essential for deep cell deoxygenation and glycolytic ATP flux. Nuclear accumulation of HIF-1α dramatically decreased upon inhibition of glutaminolysis or glutamine deprivation. Elevation of HIF-2α levels was transcription-independent and associated with the activation of Akt and Erk1/2. Upon 2 h anoxia, HIF-2α levels strongly correlated with cellular ATP, produced exclusively via glycolysis. Without glucose, HIF signalling was suppressed, giving way to other regulators of cell adaptation to energy crisis, e.g. AMPK. Consequently, viability of cells deprived of O2 and glucose decreased upon inhibition of AMPK with dorsomorphin. The capacity of cells to accumulate HIF-2α decreased after 24 h glucose deprivation. This effect, associated with increased AMPKα phosphorylation, was sensitive to dorsomorphin. In chronically hypoxic cells, glutamine played no major role in HIF-2α accumulation, which became mainly glucose-dependent. Overall, the availability of O2 and metabolic substrates intricately regulates HIF signalling by affecting cell oxygenation, ATP levels and pathways involved in production of HIF-α. - Highlights: • Gln and Glc regulate HIF levels in hypoxic cells by maintaining low O2 and high ATP. • HIF-α levels under anoxia correlate with cellular ATP and critically depend on Glc. • Gln and Glc modulate activity of Akt, Erk and AMPK, regulating HIF production. • HIF signalling is differentially inhibited by prolonged Glc and Gln deprivation. • Unlike Glc, Gln plays no major role in HIF signalling in chronically hypoxic cells

  3. Ramadan Fasting Diet Entailed a Lipid Metabolic Disorder Among Type 2 Diabetic Obese Women

    Directory of Open Access Journals (Sweden)

    Méghit B. Khaled

    2009-01-01

    Full Text Available We designed this study to assess the effect of diet during Ramadan fasting on body weight and on serum lipid components in type 2 diabetic obese women. During Ramadan of 2005, 89 diabetic women receiving oral treatment (BMI = 33.20±3.01 kg m-2, aged 52 (±5 years, were selected. The study was carried out over 3 periods-, before (T1: pre-fasting, during (T2: fasting, and after (T3: post-fasting Ramadan-in Sidi-bel-Abbes city. The daily food intake during the course of 3 days was recorded, and then weight, height, waist and hip circumferences, Body Mass Index (BMI and Waist to Hip Ratio (WHR were measured. Blood samples were analyzed for total cholesterol (TC, low-density lipoprotein cholesterol (LDL-c, high-density lipoprotein cholesterol (HDL-c, apolipoprotein A1 (apoA-I, apolipoprotein B (apoB, triglycerides (TGs, fasting serum glucose (FSG, and glycated haemoglobin (HbA1c and results were compared using Student’s t-test. The dietary fat consumption increased during Ramadan, especially for the saturated one and as a result induced a major lipid unbalance, marked by a disorder observed in nearly all of the serum lipid components. There was a significant weight loss in diabetic women (-2.56 kg, p2 = 0.313, p-1 compared to T1 (9.23±1.08 mmol L-1. Our study showed a significant weight loss during Ramadan period and an improvement of glucose homeostasis. However, the lipid metabolism was imbalanced and was strongly linked to the Ramadan diet and to the eating habits modification.

  4. Effects of a farnesoid X receptor antagonist on hepatic lipid metabolism in primates.

    Science.gov (United States)

    Amano, Yuichiro; Shimada, Mitsuyuki; Miura, Shotaro; Adachi, Ryutaro; Tozawa, Ryuichi

    2014-01-15

    We aimed to elucidate the mechanism underlying the anti-dyslipidemic effect of compound-T3, a farnesoid X receptor antagonist, by investigating its effects on hepatic lipid metabolism in non-human primates. We administered lipid-lowering drugs for 7 days to cynomolgus monkeys receiving a high-fat diet, and subsequently measured the levels of lipid parameters in plasma, feces, and hepatic tissue fluids. Compound-T3 (0.3 and 3mg/kg p.o.) significantly decreased the plasma levels of non-high-density lipoprotein (non-HDL) cholesterol and apolipoprotein B in a dose-dependent manner. It also decreased the mRNA levels of hepatic small heterodimer partner-1, induced the mRNA expression of hepatic cholesterol 7α-hydroxylase, reduced hepatic cholesterol and triglyceride levels, increased fecal bile acid excretion, and upregulated the expression of hepatic low-density lipoprotein (LDL) receptor. Furthermore, compound-T3 significantly increased plasma HDL cholesterol and apolipoprotein A-I levels. The mRNA expression levels of hepatic apolipoprotein A-I tended to increase after compound-T3 treatment. Compound-T3 also induced accumulation of hepatic bile acids and decreased the mRNA expression levels of the hepatic bile acid export pump. The effects of cholestyramine (300mg/kg p.o.) on the plasma and hepatic lipid parameters were similar to those of compound-T3, and it increased fecal bile acid levels without causing accumulation of hepatic bile acids. These findings suggest that LDL receptor-mediated hepatic LDL incorporation due to cholesterol catabolism catalyzed by cholesterol 7α-hydroxylase decreases plasma non-HDL cholesterol levels. Upregulation of hepatic apolipoprotein A-I mRNA expression may partially contribute to the increase in HDL cholesterol levels mediated by compound-T3. PMID:24361308

  5. Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets

    OpenAIRE

    Ryan D Michalek; Gerriets, Valerie A.; Jacobs, Sarah R.; Macintyre, Andrew N.; MacIver, Nancie J.; Mason, Emily F.; Sullivan, Sarah A.; Nichols, Amanda G.; Rathmell, Jeffrey C.

    2011-01-01

    Stimulated CD4+ T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation p...

  6. Phylogenomic Study of Lipid Genes Involved in Microalgal Biofuel Production—Candidate Gene Mining and Metabolic Pathway Analyses

    OpenAIRE

    Barada Kanta Mishra; Bikram Kumar Parida; Prasanna Kumar Panda; Namrata Misra

    2012-01-01

    Optimizing microalgal biofuel production using metabolic engineering tools requires an in-depth understanding of the structure-function relationship of genes involved in lipid biosynthetic pathway. In the present study, genome-wide identification and characterization of 398 putative genes involved in lipid biosynthesis in Arabidopsis thaliana Chlamydomonas reinhardtii, Volvox carteri, Ostreococcus lucimarinus, Ostreococcus tauri and Cyanidioschyzon merolae was undertaken on the basis of their...

  7. The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation

    Directory of Open Access Journals (Sweden)

    Zarbock Ralf

    2012-03-01

    Full Text Available Abstract Background Surfactant protein C (SP-C is important for the function of pulmonary surfactant. Heterozygous mutations in SFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects. Methods SP-CA116D was expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide. Results Stable expression of SP-CA116D in MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116D expression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116D cells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+ lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116D on neighboring cells in the alveolar space. Conclusions We show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy

  8. An acetone bio-sniffer (gas phase biosensor) enabling assessment of lipid metabolism from exhaled breath.

    Science.gov (United States)

    Ye, Ming; Chien, Po-Jen; Toma, Koji; Arakawa, Takahiro; Mitsubayashi, Kohji

    2015-11-15

    Several volatile organic compounds (VOCs) are released from human breath or skin. Like chemical substances in blood or urine, some of these vapors can provide valuable information regarding the state of the human body. A highly sensitive acetone biochemical gas sensor (bio-sniffer) was developed and used to measure exhaled breath acetone concentration, and assess lipid metabolism based on breath acetone analysis. A fiber-optic biochemical gas sensing system was constructed by attaching a flow-cell with nicotinamide adenine dinucleotide (NADH)-dependent secondary alcohol dehydrogenase (S-ADH) immobilized membrane onto a fiber-optic NADH measurement system. The NADH measurement system utilizes an ultraviolet-light emitting diode with peak emission of 335 nm as an excitation light source. NADH is consumed by the enzymatic reaction of S-ADH, and the consumption is proportional to the concentration of acetone vapor. Phosphate buffer which contained NADH was circulated into the flow-cell to rinse products and the excessive substrates from the optode. The change of fluorescent emitted from NADH is analyzed by the PMT. Hence, fluorescence intensity decreased as the acetone concentration increased. The relationship between fluorescence intensity and acetone concentration was identified from 20 ppb to 5300 ppb. This interval included the concentration of acetone vapor in the breath of healthy people and those suffering from disorders of carbohydrate metabolism. Finally, the acetone bio-sniffer was used to measure breath acetone during an exercise stress test on an ergometer after a period of fasting. The concentration of acetone in breath was shown to significantly increase after exercise. This biosensor allows rapid, highly sensitive and selective measurement of lipid metabolism. PMID:26079672

  9. A remedy against obesity? The role of lactoferrin in the metabolism of glucose and lipids

    Directory of Open Access Journals (Sweden)

    Jolanta Artym

    2012-11-01

    Full Text Available Obesity, dyslipidemia, hyperglycemia/type II diabetes and hypertension together constitute the so-called metabolic syndrome. Frequency of occurrence of these serious metabolic disturbances is associated with life style and is on the rise in prosperous industrialized countries. These diseases represent not only a serious health problem but also social and economic ones, and involve in prophylaxis and treatment various specialists (physicians, dieticians and psychologists. For about two decades research has been conducted on the possibility to apply milk-derived proteins in prevention and treatment of the above mentioned metabolic diseases. Lactoferrin (LF, a protein present in milk and excretory fluids of mammals, is one of the most intensively studied milk proteins for therapeutic application. Initial trials revealing an advantageous effect of LF on lipid metabolism and obesity enrolled only a few volunteers and were performed in Japan in 2003. Subsequent trials were conducted on animals as well as in clinics, and the positive results were supported by in vitro tests. After oral administration of LF, decreases of body weight, waist measurement, visceral fat tissue, plasma and liver fatty acid concentrations, triglycerides and cholesterol were registered. The mechanism of LF action may involve several processes, such as inhibition of adipogenesis, decrease of dietary triglyceride absorption, elevation of HDL cholesterol possessing anti-atherogenic properties, inhibition of accumulation of oxidized LDL cholesterol forms in macrophages and protection against formation of foam cells. LF also increases the susceptibility of cells to insulin action, including in conditions when the response to insulin is lowered (during inflammation. In addition, LF regulates activity of insulin-like growth factor (IGF. The data collected to date indicate that LF is a promising, completely nontoxic, natural remedy which (as for example a food supplement may be applied

  10. Varying plant protein sources in the diet of sea bass Dicentrarchus labrax differently affects lipid metabolism and deposition

    Directory of Open Access Journals (Sweden)

    E. Tibaldi

    2010-04-01

    Full Text Available The liver activity of lipogenic enzymes, the lipid content in various tissues, and plasma lipid levels of major, were measured in sea bass (D. labrax fed over 96 days either a, fish meal-based control diet or preparations where 70% of fish meal protein was replaced by wheat gluten singly or in combination with pea or soybean meals. Relative to the controls, sea bass fed the wheat gluten-based diet resulted in stimulated lipogenesis in liver and increased lipid deposition in muscle. The opposite occurred when a substantial amount of soybean meal was included in the diet. Mesenteric fat depots were apparently insensitive to major changes in dietary protein source in fish showing similar intakes of digestible protein, energy and lipid. These results confirm that varying plant protein source in the diet differently affects lipid metabolism and deposition in sea bass.

  11. Gastrodia elata Ameliorates High-Fructose Diet-Induced Lipid Metabolism and Endothelial Dysfunction

    Directory of Open Access Journals (Sweden)

    Min Chul Kho

    2014-01-01

    Full Text Available Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1 and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPKα in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome.

  12. Hyaluronic Acid-Modified Cationic Lipid-PLGA Hybrid Nanoparticles as a Nanovaccine Induce Robust Humoral and Cellular Immune Responses.

    Science.gov (United States)

    Liu, Lanxia; Cao, Fengqiang; Liu, Xiaoxuan; Wang, Hai; Zhang, Chao; Sun, Hongfan; Wang, Chun; Leng, Xigang; Song, Cunxian; Kong, Deling; Ma, Guilei

    2016-05-18

    Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred. Moreover, HA-DOTAP-PLGA NPs led to the up-regulation of MHC, costimulatory molecules, and cytokines. In vivo experiments further revealed that more powerful immune responses were induced from mice immunized with HA-DOTAP-PLGA NPs when compared with cationic lipid-PLGA nanoparticles and free ovalbumin (OVA); the responses included antigen-specific CD4(+) and CD8(+) T-cell responses, the production of antigen-specific IgG antibodies and the generation of memory CD4(+) and CD8(+) T cells. Overall, these data demonstrate the high potential of HA-DOTAP-PLGA NPs for use as vaccine delivery vehicles to elevate cellular and humoral immune responses. PMID:27088457

  13. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  14. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    International Nuclear Information System (INIS)

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  15. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.; Nielsen, Jens

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... is similar to the overflow metabolism observed in many other microorganisms, e.g. ethanol production by Sacchromyces cerevisiae at nitrogen limitation....

  16. ROLE OF PHYSICAL EXERCISE, FITNESS AND AEROBIC TRAINING IN TYPE 1 DIABETIC AND HEALTHY MEN IN RELATION TO THE LIPID PROFILE, LIPID PEROXIDATION AND THE METABOLIC SYNDROME

    Directory of Open Access Journals (Sweden)

    David E. Laaksonen

    2003-06-01

    Full Text Available Dyslipidemia and possibly lipid peroxidation play important roles in the development of macro- and microvascular disease in type 1 diabetes mellitus. Little is known, however, of the role of aerobic exercise in dyslipidemia and resting and exercise-induced lipid peroxidation in type 1 diabetes. Despite the well-known effect of leisure-time physical activity (LTPA on components of the metabolic syndrome, little is known of the association of LTPA and cardiorespiratory fitness (maximal oxygen consumption, VO2max with development of the metabolic syndrome itself. A randomized controlled trial assessing the effect of a 12-16 week aerobic exercise program on VO2max and the lipid profile was carried out in otherwise healthy young men with type 1 diabetes. The effect of acute physical exercise on oxidative stress and antioxidant defenses and the relation to VO2max in men with type 1 diabetes was also evaluated. To test four recently proposed definitions by the World Health Organization (WHO and National Cholesterol Education Program (NCEP of the metabolic syndrome, the sensitivity and specificity of the definitions for prevalent and incident diabetes were assessed in a population-based cohort of middle-aged men. We also studied the associations of LTPA and cardiorespiratory fitness with prevalent and incident cases of the metabolic syndrome. A 12-16 week endurance exercise program produced antiatherogenic changes in lipid, lipoprotein and apolipoprotein levels in 20 type 1 diabetic men who for the most part were already physically active at baseline. The most favorable training-induced changes in the high-density lipoprotein cholesterol (HDL/low-density lipoprotein cholesterol (LDL and apolipoprotein A-I/apolipoprotein B ratios were in patients with low baseline HDL/LDL levels, likely the group with the most benefit to be gained by such changes. Plasma thiobarbituric acid reactive substances (TBARS, a measure of lipid peroxidation, was higher in nine

  17. mRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas

    International Nuclear Information System (INIS)

    Highlights: •Genes regulating lipid metabolism were studied in ringed seals. •We compared highly contaminated Baltic seals and less contaminated Svalbard seals. •mRNA expression of hepatic PPARγ was higher in the Baltic seals. •mRNA expression of adipose PPARγ target genes was higher in the Baltic seals. •Contaminant exposure may affect lipid metabolism in the Baltic ringed seals. -- Abstract: There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes

  18. mRNA expression of genes regulating lipid metabolism in ringed seals (Pusa hispida) from differently polluted areas

    Energy Technology Data Exchange (ETDEWEB)

    Castelli, Martina Galatea [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway); University of Bergen, Department of Biology, 5020 Bergen (Norway); Rusten, Marte; Goksøyr, Anders [University of Bergen, Department of Biology, 5020 Bergen (Norway); Routti, Heli, E-mail: heli.routti@npolar.no [Norwegian Polar Institute, Fram Centre, 9296 Tromsø (Norway)

    2014-01-15

    Highlights: •Genes regulating lipid metabolism were studied in ringed seals. •We compared highly contaminated Baltic seals and less contaminated Svalbard seals. •mRNA expression of hepatic PPARγ was higher in the Baltic seals. •mRNA expression of adipose PPARγ target genes was higher in the Baltic seals. •Contaminant exposure may affect lipid metabolism in the Baltic ringed seals. -- Abstract: There is a growing concern about the ability of persistent organic pollutants (POPs) to influence lipid metabolism. Although POPs are found at high concentrations in some populations of marine mammals, for example in the ringed seal (Pusa hispida) from the Baltic Sea, little is known about the effects of POPs on their lipid metabolism. An optimal regulation of lipid metabolism is crucial for ringed seals during the fasting/molting season. This is a physiologically stressful period, during which they rely on the energy stored in their fat reserves. The mRNA expression levels for seven genes involved in lipid metabolism were analyzed in liver and/or blubber tissue from molting ringed seals from the polluted Baltic Sea and a less polluted reference location, Svalbard (Norway). mRNA expression of genes encoding peroxisome proliferator-activated receptors (PPAR) α and γ and their target genes acyl-coenzyme A oxidase 1 (ACOX1) and cluster of differentiation 36 (CD36) were analyzed in liver. mRNA expression level of genes encoding PPARβ, PPARγ and their target genes encoding fatty acid binding protein 4 (FABP4) and adiponectin (ADIPOQ) were measured in inner and middle blubber layers. In addition, we evaluated the influence of molting status on hepatic mRNA expression of genes encoding PPARs and their target genes in ringed seals from Svalbard. Our results show higher mRNA expression of genes encoding hepatic PPARγ and adipose PPARβ, FABP4, and ADIPOQ in the Baltic seals compared to the Svalbard seals. A positive relationship between mRNA expressions of genes

  19. DIFFERENTIAL-EFFECTS OF METABOLIC-INHIBITORS ON CELLULAR AND MITOCHONDRIAL UPTAKE OF ORGANIC CATIONS IN RAT-LIVER

    NARCIS (Netherlands)

    STEEN, H; MARING, JG; MEIJER, DKF

    1992-01-01

    The effects of several metabolic inhibitors on the uptake of tri-n-butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-Mediated uptake and cellular accumula

  20. Effect of fenitrothion and disulfoton on lipid metabolism in tissues of white leghorn chicks (Gallus domesticus)

    International Nuclear Information System (INIS)

    The effects of acute and chronic toxicity due to Disulfoton (diethyl S-(2-ehtyl thio) ethyl phosphorothionate) and Fenitrothion (dimethyl P-3-methyl-4 nitrophenyl phosphorothionate) on the lipid metabolism in tissues of white leghorn chicks (Gallus domesticus) was studied by using 32P-phosphate, 2-14C-acetate and U-14C-glucose as precursors. During acute toxicity, the biosynthesis of fatty acids and aerobic oxidation of glucose appear to be inhibited in nervous tissues. However, during chronic toxicity, the biosynthesis of fatty acids is not inhibited. The biosynthesis of phospholipids is depressed in certain tissues due to decreased availability of diglyceride precursors during acute toxicity. During chronic toxicity, the formation of diglyceride from phosphatidic acid appears to be inhibited. (author). 14 refs., 4 tabs

  1. Microscopic mechanism analyses on influence of metabolism of erythrocyte membrane-lipid etc. by LLLIB

    Science.gov (United States)

    Xu, Lin; Zhang, Canbang; Wen, Yuanbin; Liu, Shuxiao; Zhou, Lingyun

    2009-08-01

    Some cases with cerebral infarction were treated by He-Ne laser irradiation on blood. In the treatment before and after, membrane-cholesterol(C)/membrane-phosphatide(P), membrane fluidity(F) and deformability of erythrocyte were determined. The results showed that low level laser irradiation on blood (LLLIB) can sure reduce the ratio of (C)/(P), can heighten fluidity and improve deformability of erythrocyte .Thus the metabolism ability of erythrocyte membrane-lipid ,the blood circulation and the properties of hemorheology can be improved. In this paper, the microscopic mechanism of those aforesaid action effects by low level laser irradiation on blood were analyzed by means of Quantum theory and some corresponding models.

  2. Hepatic Lipase: a Comprehensive View of its Role on Plasma Lipid and Lipoprotein Metabolism.

    Science.gov (United States)

    Kobayashi, Junji; Miyashita, Kazuya; Nakajima, Katsuyuki; Mabuchi, Hiroshi

    2015-01-01

    Hepatic lipase (HL) is a key enzyme catalyzing the hydrolysis of triglycerides (TG) and phospholipids (PLs) in several lipoproteins. It is generally recognized that HL is involved in the remodeling of remnant, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and the production of small, dense low-density lipoproteins (sd-LDLs).On the other hand, it is unclear whether HL accelerates or retards atherosclerosis. From the clinical point of view, HL deficiency may provide useful information on answering this question, but the rarity of this disease makes it impossible to conduct epidemiological study.In this review, we describe a comprehensive and updated view of the clinical significance of HL on lipid and lipoprotein metabolism. PMID:26194979

  3. Regulation effects of Crataegus pinnatifida leaf on glucose and lipids metabolism.

    Science.gov (United States)

    Wang, Tao; An, Yating; Zhao, Chunfeng; Han, Lifeng; Boakye-Yiadom, Mavis; Wang, Wei; Zhang, Yi

    2011-05-11

    The leaf of Crataegus pinnatifida (Rosaceae) is commonly consumed either raw or cooked to improve digestion and promote blood circulation in China. To investigate the regulation effects of it on glucose and lipid metabolism, the flavonoids fraction was prepared and analyzed by HPLC and LC-MS. In vivo, at doses of 250 and 500 mg/kg, the flavonoids fraction showed inhibitory effects on TG and glucose absorption, accelerating effects on gastrointestinal transit but no effect on gastric emptying. In vitro, treatment of 3T3-L1 preadipocytes with 30 μg/mL flavonoids fraction significantly suppressed the accumulation of TG and free fatty acid. It also suppressed the gene expressions of C/EBPα, PPARγ, SREBP 1c, aP2 and adiponectin but did not affect that of leptin. C. pinnatifida leaf may be useful for type 2 diabetics and hyperlipidemics as a foodstuff. PMID:21425878

  4. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  5. Surfactant Lipids at the Host-Environment Interface. Metabolic Sensors, Suppressors, and Effectors of Inflammatory Lung Disease.

    Science.gov (United States)

    Fessler, Michael B; Summer, Ross S

    2016-05-01

    The lipid composition of pulmonary surfactant is unlike that of any other body fluid. This extracellular lipid reservoir is also uniquely susceptible by virtue of its direct and continuous exposure to environmental oxidants, inflammatory agents, and pathogens. Historically, the greatest attention has been focused on those biophysical features of surfactant that serve to reduce surface tension at the air-liquid interface. More recently, surfactant lipids have also been recognized as bioactive molecules that maintain immune quiescence in the lung but can also be remodeled by the inhaled environment into neolipids that mediate key roles in inflammation, immunity, and fibrosis. This review focuses on the roles in inflammatory and infectious lung disease of two classes of native surfactant lipids, glycerophospholipids and sterols, and their corresponding oxidized species, oxidized glycerophospholipids and oxysterols. We highlight evidence that surfactant composition is sensitive to circulating lipoproteins and that the lipid milieu of the alveolus should thus be recognized as susceptible to diet and common systemic metabolic disorders. We also discuss intriguing evidence suggesting that oxidized surfactant lipids may represent an evolutionary link between immunity and tissue homeostasis that arose in the primordial lung. Taken together, the emerging picture is one in which the unique environmental susceptibility of the lung, together with its unique extracellular lipid requirements, may have made this organ both an evolutionary hub and an engine for lipid-immune cross-talk. PMID:26859434

  6. Topographical body fat distribution links to amino acid and lipid metabolism in healthy obese women [corrected].

    Directory of Open Access Journals (Sweden)

    Francois-Pierre J Martin

    Full Text Available Visceral adiposity is increasingly recognized as a key condition for the development of obesity related disorders, with the ratio between visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT reported as the best correlate of cardiometabolic risk. In this study, using a cohort of 40 obese females (age: 25-45 y, BMI: 28-40 kg/m(2 under healthy clinical conditions and monitored over a 2 weeks period we examined the relationships between different body composition parameters, estimates of visceral adiposity and blood/urine metabolic profiles. Metabonomics and lipidomics analysis of blood plasma and urine were employed in combination with in vivo quantitation of body composition and abdominal fat distribution using iDXA and computerized tomography. Of the various visceral fat estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant associations with regio-specific body lean and fat composition. The integration of these visceral fat estimates with metabolic profiles of blood and urine described a distinct amino acid, diacyl and ether phospholipid phenotype in women with higher visceral fat. Metabolites important in predicting visceral fat adiposity as assessed by Random forest analysis highlighted 7 most robust markers, including tyrosine, glutamine, PC-O 44∶6, PC-O 44∶4, PC-O 42∶4, PC-O 40∶4, and PC-O 40∶3 lipid species. Unexpectedly, the visceral fat associated inflammatory profiles were shown to be highly influenced by inter-days and between-subject variations. Nevertheless, the visceral fat associated amino acid and lipid signature is proposed to be further validated for future patient stratification and cardiometabolic health diagnostics.

  7. Subchronic effects of valproic acid on gene expression profiles for lipid metabolism in mouse liver

    International Nuclear Information System (INIS)

    Valproic acid (VPA) is used clinically to treat epilepsy, however it induces hepatotoxicity such as microvesicular steatosis. Acute hepatotoxicity of VPA has been well documented by biochemical studies and microarray analysis, but little is known about the chronic effects of VPA in the liver. In the present investigation, we profiled gene expression patterns in the mouse liver after subchronic treatment with VPA. VPA was administered orally at a dose of 100 mg/kg/day or 500 mg/kg/day to ICR mice, and the livers were obtained after 1, 2, or 4 weeks. The activities of serum liver enzymes did not change, whereas triglyceride concentration increased significantly. Microarray analysis revealed that 1325 genes of a set of 32,996 individual genes were VPA responsive when examined by two-way ANOVA (P 1.5). Consistent with our previous results obtained using an acute VPA exposure model (Lee et al., Toxicol Appl Pharmacol. 220:45-59, 2007), the most significantly over-represented biological terms for these genes included lipid, fatty acid, and steroid metabolism. Biological pathway analysis suggests that the genes responsible for increased biosynthesis of cholesterol and triglyceride, and for decreased fatty acid β-oxidation contribute to the abnormalities in lipid metabolism induced by subchronic VPA treatment. A comparison of the VPA-responsive genes in the acute and subchronic models extracted 15 commonly altered genes, such as Cyp4a14 and Adpn, which may have predictive power to distinguish the mode of action of hepatotoxicants. Our data provide a better understanding of the molecular mechanisms of VPA-induced hepatotoxicity and useful information to predict steatogenic hepatotoxicity

  8. Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification

    International Nuclear Information System (INIS)

    Serine hydrolase KIAA1363 is an acetyl monoalkylglycerol ether (AcMAGE) hydrolase involved in tumor cell invasiveness. It is also an organophosphate (OP) insecticide-detoxifying enzyme. The key to understanding these dual properties was the use of KIAA1363 +/+ (wildtype) and -/- (gene deficient) mice to define the role of this enzyme in brain and other tissues and its effectiveness in vivo in reducing OP toxicity. KIAA1363 was the primary AcMAGE hydrolase in brain, lung, heart and kidney and was highly sensitive to inactivation by chlorpyrifos oxon (CPO) (IC50 2 nM) [the bioactivated metabolite of the major insecticide chlorpyrifos (CPF)]. Although there was no difference in hydrolysis product monoalkylglycerol ether (MAGE) levels in +/+ and -/- mouse brains in vivo, isopropyl dodecylfluorophosphonate (30 mg/kg) and CPF (100 mg/kg) resulted in 23-51% decrease in brain MAGE levels consistent with inhibition of AcMAGE hydrolase activity. On incubating +/+ and -/- brain membranes with AcMAGE and cytidine-5'-diphosphocholine, the absence of KIAA1363 activity dramatically increased de novo formation of platelet-activating factor (PAF) and lyso-PAF, signifying that metabolically-stabilized AcMAGE can be converted to this bioactive lipid in brain. On considering detoxification, KIAA1363 -/- mice were significantly more sensitive than +/+ mice to ip-administered CPF (100 mg/kg) and parathion (10 mg/kg) with increased tremoring and mortality that correlated for CPF with greater brain acetylcholinesterase inhibition. Docking AcMAGE and CPO in a KIAA1363 active site model showed similar positioning of their acetyl and trichloropyridinyl moieties, respectively. This study establishes the relevance of KIAA1363 in ether lipid metabolism and OP detoxification

  9. In vivo and in vitro studies of hepatic lipid metabolism in lean and reobese fetal pigs

    International Nuclear Information System (INIS)

    Fetuses were removed from pregnant (110 days of gestation) sows and 80 to 120 mg liver slices were prepared for two hour incubations with 14C-palmitate (1 μCi/ml) or 3H2O (1 mCi/ml). In vivo studies were conducted by injecting a single bolus of 0.5 or 10 ml of Liposyn (a 10% safflower oil emulsion) into fetuses (umbilical vein). One hour post injection (Liposyn) fetuses were removed from the uterus. Subsequently liver lipids were extracted and gas chromatographic analysis for 16:0, 18:0, 18:1, 18:2 and 20:4 were performed. Incorporation of C14-palmitate into total lipids was higher in lean livers whereas incorporation into CO2 was independent of fetal strain. Incorporation of 3H2O into triglyceride fatty acids was similar in lean and obese livers. Fatty acid composition of livers indicated strain differences (obese versus lean for 16:0 = 52 vs 27.8%; 18:0 = 20 vs 16.8%; 18:1 = 16.3 vs 32.6%; 20:4 = 8.8 vs 17.6%). There was a similar Liposyn dose dependent increase in the amount of 18:2 in chromatographs of lean (n = 7) and obese (n = 7) livers. Administration of Liposyn caused a significant increase in the amount of 18:1 and 20:4 in lean livers (least squares means +/- SEM, 0 vs 0.5 ml for 20:4 = .31 +/- .03 vs .48 +/- .04) but no increase in preobese livers. These studies illustrate significant alterations in hepatic lipid metabolism in the preobese state

  10. Dietary fat interacts with PCBs to induce changes in lipid metabolism in LDL receptor deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Hennig, B.; Reiterer, G.; Toborek, M.; Matveev, S.V.; Daugherty, A.; Smart, E. [Univ. of Kentucky, Lexington (United States); Robertson, L.W. [Univ. of Iowa, Iowa City (United States)

    2004-09-15

    From epidemiological studies, there is substantial evidence that cardiovascular diseases are linked to environmental pollution and that exposure to polycyclic and/or polyhalogenated aromatic hydrocarbons can lead to human cardiovascular toxicity. A major route of exposure to PCBs in humans is via oral ingestion of contaminated food products. Therefore, circulating environmental contaminants derived from diets, such as PCBs, are in intimate contact with the vascular endothelium. Endothelial activation and dysfunction is an important factor in the overall regulation of vascular lesion pathology. In addition to endothelial barrier dysfunction, another functional change in atherosclerosis is the activation of the endothelium that is manifested as an increase in the expression of specific cytokines and adhesion molecules. These cytokines and adhesion molecules are proposed to mediate the inflammatory aspects of the disease by regulating the vascular entry of leukocytes. Alterations in lipid profile and lipid metabolism as a result of exposure to PCBs may be important components of endothelial cell dysfunction. Little is known about the interaction of dietary fats and PCBs in the pathology of atherosclerosis. We have reported a significant disruption in endothelial barrier function when cells were exposed to linoleic acid. In the current study we aimed to demonstrate the PCB-fatty acid interaction in vivo and hypothesized that PCB toxicity can be modulated by the type of fat consumed.

  11. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Science.gov (United States)

    Caimi, Gregorio; Lo Presti, Rosalia; Montana, Maria; Canino, Baldassare; Averna, Maurizio R.

    2014-01-01

    Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), nitric oxide metabolites (nitrite + nitrate) expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS). In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS) and nondiabetic (NDMS) and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C) index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index. PMID:24987495

  12. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    Science.gov (United States)

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  13. Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Gregorio Caimi

    2014-01-01

    Full Text Available Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS, nitric oxide metabolites (nitrite + nitrate expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS. In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS and nondiabetic (NDMS and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NOx ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index.

  14. Effects of defatted amaranth (Amaranthus caudatus L. snacks on lipid metabolism of patients with moderate hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Rosa Nilda Chávez-Jáuregui

    2010-12-01

    Full Text Available We evaluated the effects of defatted amaranth (Amaranthus caudatus L. snacks on plasma lipids in moderate hypercholesterolemic patients. Twenty-two subjects [30-65 years old, 11 males, with total cholesterol (TC > 240 mg.dL-1, low-density cholesterol (LDL-c 160-190 mg.dL-1 and plasma triglycerides (TG < 400 mg.dL-1] were randomized in a double blind clinical trial to receive an amaranth snack (50 g/day or equivalent corn snack (placebo for 2 months. There were no differences between amaranth and placebo on TC and LDL-c, and TG respectively: -8.4 and -5.7% (p = 0.17; -12.3 and -9.7% (p = 0.41 and -0.6 and -7.3% (p = 0.47. However, amaranth snacks significantly reduced high-density cholesterol (HDL-c: -15.2 vs. -4% (p = 0.03. In conclusion, the intake of 50 g of extruded amaranth daily during 60 days did not significantly reduce LDL-c in moderate hypercholesterolemic subjects; furthermore there was a significant reduction in HDL-c. Studies with greater number of subjects and greater quantity of this food are necessary to test the effects of amaranth on lipid metabolism in humans.

  15. Soy Germ Protein With or Without-Zn Improve Plasma Lipid Profile in Metabolic Syndrome Women

    Directory of Open Access Journals (Sweden)

    SIWI PRAMATAMA MARS WIJAYANTI

    2012-03-01

    Full Text Available The aim of this research was to determine the effect of soy germ protein on lipid profile of metabolic syndrome (MetS patients. Respondents were 30 women with criteria, i.e. blood glucose level > normal, body mass index > 25 kg/m2, hypertriglyceridemia, low cholesterol-HDL level, 40-65 years old, living in Purwokerto, and signed the informed consent. The project was approved by the ethics committee of the Medical Faculty from Gadjah Mada University-Yogyakarta. Respondents were divided into three randomly chosen groups consisting of ten women each. The first, second, and third groups were treated, respectively, with milk enriched soy germ protein plus Zn, milk enriched soy germ protein (without Zn, and placebo for two months. Blood samples were taken at baseline, one and two months after observation. Two months after observation the groups consuming milk enriched with soy germ protein, both with or without Zn, had their level of cholesterol-total decrease from 215.8 to 180.2 mg/dl (P = 0.03, triglyceride from 240.2 to 162.5 mg/dl (P = 0.02, and LDL from 154.01 to 93.85 mg/dl (P = 0.03. In contrast, HDL increased from 38.91 to 49.49 mg/dl (P = 0.0008. In conclusion, soy germ protein can improve lipid profile, thus it can inhibit atherosclerosis incident.

  16. C333H, a novel PPARα/γ dual agonist, has beneficial effects on insulin resistance and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Cheng XU; Li-li WANG; Hong-ying LIU; Xing-bo ZHOU; Ying-lin CAO; Song LI

    2006-01-01

    Aim: To examine the effects of novel peroxisome proliferator-activated receptor (PPAR) α/γdual agonist C333H on insulin resistance and lipid metabolism.Methods: An established dual-luciferase reporter gene assay system was used in vitro to test the activity of C333H with respect to the transcription of human PPARα and PPARγ. A preadipocyte differentiation assay and reverse transcription-polymerase chain reaction were used to detect the functional activities of C333H. In db/db mice, the effects of C333H were investigated with respect to lowering of blood glucose and lipid levels. Results: C333H was determined to be a novel PPARα/γ dual agonist because it strongly induced luciferase activity on human PPARα and PPARγ, promoting the differentiation of preadipocytes to adipocytes, and functioning in upregulating the expression of some glucose and lipid metabolic target genes of the PPAR. In addition, C333H efficiently reduced blood lipid and glucose concentrations in db/db diabetic mice. Conclusion: C333H has dual action on both PPARα and PPARγ, and might be of interest for the amelioration of lipid metabolic disorders and insulin resistance associated with type 2 diabetes.

  17. Phylogenomic study of lipid genes involved in microalgal biofuel production-candidate gene mining and metabolic pathway analyses.

    Science.gov (United States)

    Misra, Namrata; Panda, Prasanna Kumar; Parida, Bikram Kumar; Mishra, Barada Kanta

    2012-01-01

    Optimizing microalgal biofuel production using metabolic engineering tools requires an in-depth understanding of the structure-function relationship of genes involved in lipid biosynthetic pathway. In the present study, genome-wide identification and characterization of 398 putative genes involved in lipid biosynthesis in Arabidopsis thaliana Chlamydomonas reinhardtii, Volvox carteri, Ostreococcus lucimarinus, Ostreococcus tauri and Cyanidioschyzon merolae was undertaken on the basis of their conserved motif/domain organization and phylogenetic profile. The results indicated that the core lipid metabolic pathways in all the species are carried out by a comparable number of orthologous proteins. Although the fundamental gene organizations were observed to be invariantly conserved between microalgae and Arabidopsis genome, with increased order of genome complexity there seems to be an association with more number of genes involved in triacylglycerol (TAG) biosynthesis and catabolism. Further, phylogenomic analysis of the genes provided insights into the molecular evolution of lipid biosynthetic pathway in microalgae and confirm the close evolutionary proximity between the Streptophyte and Chlorophyte lineages. Together, these studies will improve our understanding of the global lipid metabolic pathway and contribute to the engineering of regulatory networks of algal strains for higher accumulation of oil. PMID:23032611

  18. Endoplasmic Reticulum Stress May Play a Pivotal Role in Lipid Metabolic Disorders in a Novel Mouse Model of Subclinical Hypothyroidism

    Science.gov (United States)

    Zhou, Lingyan; Ding, Shuyan; Li, Yujie; Wang, Laicheng; Chen, Wenbin; Bo, Tao; Wu, Kunpeng; Li, Congcong; Liu, Xiaojing; Zhao, Jiajun; Xu, Chao; Gao, Ling

    2016-01-01

    Subclinical hypothyroidism (SCH) is becoming a global health problem due to its increasing prevalence and potential deleterious effects. However, the molecular mechanisms underlying the lipid metabolic disorders in SCH have not been fully clarified. Additionally, progress in elucidating the exact pathogenesis of SCH has been hampered by the lack of optimized mouse models. Methimazole (MMI) was applied to construct a noninvasive SCH mouse model. Eight-week-old C57BL/6 mice were administrated MMI through the drinking water. After 12 weeks, the MMI-treated mice showed the diagnostic criteria for SCH: increased serum thyrotropin (TSH) levels with constant thyroid hormone levels that persisted for approximately 8 weeks. Notably, SCH mice presented evident lipid metabolic disturbances, including dyslipidemia and hepatic lipid accumulation. Further analysis showed that hepatic endoplasmic reticulum stress (ER stress) was induced in the SCH mice or by the elevation of TSH in vitro, likely via the IRE1α/XBP-1 pathway. Interestingly, when we used 4-phenyl butyric acid to repress ER stress in SCH mice for 4 weeks, dyslipidemia and hepatic lipid accumulation were both significantly alleviated. Our findings indicate that an optimized SCH mouse model could be established using MMI, and ER stress may play a pivotal role in the lipid metabolic abnormalities in SCH. PMID:27539723

  19. Endogenous and dietary lipids influencing feed intake and energy metabolism of periparturient dairy cows.

    Science.gov (United States)

    Kuhla, B; Metges, C C; Hammon, H M

    2016-07-01

    The high metabolic priority of the mammary gland for milk production, accompanied by limited feed intake around parturition results in a high propensity to mobilize body fat reserves. Under these conditions, fuel selection of many peripheral organs is switched, for example, from carbohydrate to fat utilization to spare glucose for milk production and to ensure partitioning of tissue- and dietary-derived nutrients toward the mammary gland. For example, muscle tissue uses nonesterified fatty acids (NEFA) but releases lactate and amino acids in a coordinated order, thereby providing precursors for milk synthesis or hepatic gluconeogenesis. Tissue metabolism and in concert, nutrient partitioning are controlled by the endocrine system involving a reduction in insulin secretion and systemic insulin sensitivity and orchestrated changes in plasma hormones such as insulin, adiponectin, insulin growth factor-I, growth hormone, glucagon, leptin, glucocorticoids, and catecholamines. However, the endocrine system is highly sensitive and responsive to an overload of fatty acids no matter if excessive NEFA supply originates from exogenous or endogenous sources. Feeding a diet containing rumen-protected fat from late lactation to calving and beyond exerts similar negative effects on energy intake, glucose and insulin concentrations as does a high extent of body fat mobilization around parturition in regard to the risk for ketosis and fatty liver development. High plasma NEFA concentrations are thought not to act directly at the brain level, but they increase the energy charge of the liver which is, signaled to the brain to diminish feed intake. Cows differing in fat mobilization during the transition phase differ in their hepatic energy charge, whole body fat oxidation, glucose metabolism, plasma ghrelin, and leptin concentrations and in feed intake several week before parturition. Hence, a high lipid load, no matter if stored, mobilized or fed, affects the endocrine system

  20. JAK and STAT members of yellow catfish Pelteobagrus fulvidraco and their roles in leptin affecting lipid metabolism.

    Science.gov (United States)

    Wu, Kun; Tan, Xiao-Ying; Xu, Yi-Huan; Chen, Qi-Liang; Pan, Ya-Xiong

    2016-01-15

    The present study clones and characterizes the full-length cDNA sequences of members in JAK-STAT pathway, explores their mRNA tissue expression and the biological role in leptin influencing lipid metabolism in yellow catfish Pelteobagrus fulvidraco. Full-length cDNA sequences of five JAKs and seven STAT members, including some splicing variants, were obtained from yellow catfish. Compared to mammals, more members of the JAKs and STATs family were found in yellow catfish, which provided evidence that the JAK and STAT family members had arisen by the whole genome duplications during vertebrate evolution. All of these members were widely expressed across the eleven tissues (liver, white muscle, spleen, brain, gill, mesenteric fat, anterior intestine, heart, mid-kidney, testis and ovary) but at the variable levels. Intraperitoneal injection in vivo and incubation in vitro of recombinant human leptin changed triglyceride content and mRNA expression of several JAKs and STATs members, and genes involved in lipid metabolism. AG490, a specific inhibitor of JAK2-STAT pathway, partially reversed leptin-induced effects, indicating that the JAK2a/b-STAT3 pathway exerts main regulating actions of leptin on lipid metabolism at transcriptional level. Meanwhile, the different splicing variants were differentially regulated by leptin incubation. Thus, our data suggest that leptin activated the JAK/STAT pathway and increases the expression of target genes, which partially accounts for the leptin-induced changes in lipid metabolism in yellow catfish. PMID:26704851

  1. Rapid Communication: Cholesterol deficiency-associated APOB mutation impacts lipid metabolism in Holstein calves and breeding bulls.

    Science.gov (United States)

    Gross, J J; Schwinn, A-C; Schmitz-Hsu, F; Menzi, F; Drögemüller, C; Albrecht, C; Bruckmaier, R M

    2016-04-01

    During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes. Independent of sex, CDS had significantly lower plasma concentrations of total cholesterol (TC), free cholesterol (FC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triacylglycerides (TAG), and phospholipids (PL) compared with homozygous wild-type calves ( plasma concentrations of TC, FC, HDL-C, LDL-C, VLDL-C, TAG, and PL were lower compared with CDF bulls ( lipid metabolism in affected Holstein calves and adult breeding bulls. Besides cholesterol, the concentrations of PL, TAG, and lipoproteins also were distinctly reduced in homozygous and heterozygous carriers of the mutation. Beyond malabsorption of dietary lipids, deleterious effects of apolipoprotein B deficiency on hepatic lipid metabolism, steroid biosynthesis, and cell membrane function can be expected, which may result in unspecific symptoms of reduced fertility, growth, and health. PMID:27136033

  2. Transcription analysis of genes involved in lipid metabolism reveals the role of chromium in reducing body fat in animal models.

    Science.gov (United States)

    Sadeghi, Mostafa; Najaf Panah, Mohammad Javad; Bakhtiarizadeh, Mohammad Reza; Emami, Ali

    2015-10-01

    Chromium was proposed to be an essential trace element over 50 years ago and has been accepted as an essential element for over 30 years. The recent studies indicated that the addition of supra nutritional amounts of chromium to the diet can only be considered as having pharmacological effects. However, the precise mechanism through which chromium acts on lipid, carbohydrate, protein and nucleic acid metabolism are relatively poor studied. To uncover, at least partially, the role of chromium in lipid metabolism, in this study, we evaluated the expression status of eight important genes, involved in fat biosynthesis and lipid metabolism, in four different tissue types (liver, subcutaneous fat, visceral fat, and longissimus muscle) in domestic goat kids feeding on three different chromium levels. The quantitative real-time PCR (RT-PCR) was established for expression analyses with HSP90 gene was used as reference gene. The results showed that supplementation of goats with 1.5mg/day chromium significantly decreases the expression of the ACC1, DGAT1, FABP4, FAS, HSL, LEP genes, but does not affect the expression of the LPL and SCD1 genes in all studied tissues. This study highlights, for the first time, the role of supra nutritional levels of chromium in lipid biosynthesis and metabolism. These findings are of especial importance for improving meat quality in domestic animals. PMID:26302911

  3. Status of carbohydrate and lipid metabolism in obese patients with type 2 diabetes mellitus after biliopancreatic diversion surgery

    Directory of Open Access Journals (Sweden)

    E V Ershova

    2013-10-01

    Full Text Available We examined 70 patients with obesity and diabetes mellitus type 2 before and within 5 years after BPD: these patients showed a significant improvement in the status of carbohydrate and lipid metabolism within 3 months after surgery. This improvement has remained stable along with the reduced body weight during the whole observation period of up to 5 years.

  4. Role of cholesterol and lipid organization in disease

    Science.gov (United States)

    Maxfield, Frederick R.; Tabas, Ira

    2005-12-01

    Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.

  5. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice.

    Science.gov (United States)

    Hoene, Miriam; Li, Jia; Li, Yanjie; Runge, Heike; Zhao, Xinjie; Häring, Hans-Ulrich; Lehmann, Rainer; Xu, Guowang; Weigert, Cora

    2016-01-01

    Intracellular lipid pools are highly dynamic and tissue-specific. Physical exercise is a strong physiologic modulator of lipid metabolism, but most studies focus on changes induced by long-term training. To assess the acute effects of endurance exercise, mice were subjected to one hour of treadmill running, and (13)C16-palmitate was applied to trace fatty acid incorporation in soleus and gastrocnemius muscle and liver. The amounts of carnitine, FFA, lysophospholipids and diacylglycerol and the post-exercise increase in acetylcarnitine were pronouncedly higher in soleus than in gastrocnemius. In the liver, exercise increased the content of lysophospholipids, plasmalogens and carnitine as well as transcript levels of the carnitine transporter. (13)C16-palmitate was detectable in several lipid and acylcarnitine species, with pronounced levels of tracer-derived palmitoylcarnitine in both muscles and a strikingly high incorporation into triacylglycerol and phosphatidylcholine in the liver. These data illustrate the high lipid storing activity of the liver immediately after exercise whereas in muscle, fatty acids are directed towards oxidation. The observed muscle-specific differences accentuate the need for single-muscle analyses as well as careful consideration of the particular muscle employed when studying lipid metabolism in mice. In addition, our results reveal that lysophospholipids and plasmalogens, potential lipid signalling molecules, are acutely regulated by physical exercise. PMID:26916151

  6. Ocean warming alters cellular metabolism and induces mortality in fish early life stages: A proteomic approach.

    Science.gov (United States)

    Madeira, D; Araújo, J E; Vitorino, R; Capelo, J L; Vinagre, C; Diniz, M S

    2016-07-01

    Climate change has pervasive effects on marine ecosystems, altering biodiversity patterns, abundance and distribution of species, biological interactions, phenology, and organisms' physiology, performance and fitness. Fish early life stages have narrow thermal windows and are thus more vulnerable to further changes in water temperature. The aim of this study was to address the sensitivity and underlying molecular changes of larvae of a key fisheries species, the sea bream Sparus aurata, towards ocean warming. Larvae were exposed to three temperatures: 18°C (control), 24°C (warm) and 30°C (heat wave) for seven days. At the end of the assay, i) survival curves were plotted for each temperature treatment and ii) entire larvae were collected for proteomic analysis via 2D gel electrophoresis, image analysis and mass spectrometry. Survival decreased with increasing temperature, with no larvae surviving at 30°C. Therefore, proteomic analysis was only carried out for 18°C and 24°C. Larvae up-regulated protein folding and degradation, cytoskeletal re-organization, transcriptional regulation and the growth hormone while mostly down-regulating cargo transporting and porphyrin metabolism upon exposure to heat stress. No changes were detected in proteins related to energetic metabolism suggesting that larval fish may not have the energetic plasticity needed to sustain cellular protection in the long-term. These results indicate that despite proteome modulation, S. aurata larvae do not seem able to fully acclimate to higher temperatures as shown by the low survival rates. Consequently, elevated temperatures seem to have bottleneck effects during fish early life stages, and future ocean warming can potentially compromise recruitment's success of key fisheries species. PMID:27062348

  7. HIV protease inhibitors disrupt lipid metabolism by activating endoplasmic reticulum stress and inhibiting autophagy activity in adipocytes.

    Directory of Open Access Journals (Sweden)

    Beth S Zha

    Full Text Available BACKGROUND: HIV protease inhibitors (PI are core components of Highly Active Antiretroviral Therapy (HAART, the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome. METHODOLOGY AND PRINCIPAL FINDINGS: Cultured and primary mouse adipocytes and human adipocytes were used to examine the effect of frequently used HIV PIs in the clinic, lopinavir/ritonavir, on adipocyte differentiation and further identify the underlying molecular mechanism of HIV PI-induced dysregulation of lipid metabolism in adipocytes. The results indicated that lopinavir alone or in combination with ritonavir, significantly activated the ER stress response, inhibited cell differentiation, and induced cell apoptosis in adipocytes. In addition, HIV PI-induced ER stress was closely linked to inhibition of autophagy activity. We also identified through the use of primary adipocytes of CHOP(-/- mice that CHOP, the major transcriptional factor of the ER stress signaling pathway, is involved in lopinavir/ritonavir-induced inhibition of cell differentiation in adipocytes. In addition, lopinavir/ritonavir-induced ER stress appears to be associated with inhibition of autophagy activity in adipocytes. CONCLUSION AND SIGNIFICANCE: Activation of ER stress and impairment of autophagy activity are involved in HIV PI-induced dysregulation of lipid metabolism in adipocytes. The key components of ER stress and autophagy signaling pathways are potential therapeutic targets for HIV PI-induced metabolic side effects in HIV patients.

  8. Role of heterogeneity of lipids in predicting risk of atheroma formation in metabolic syndrome

    International Nuclear Information System (INIS)

    Objective: Assessing impact of heterogeneous lipids in predisposing cardiovascular (CV) atheroma formation in adolescents with metabolic syndrome (MS). Study Design: Cross-sectional analytical. Place and Duration of Study: Educational Institutes of Lahore. Six months Material and Methods: A total of 193, 17-25 year old subjects, 106 males and 87 females were recruited. A record regarding each subject's personal, socioeconomic, educational, dietary and family histories was taken. They underwent the following anthropometric measurements: waist circumference/WC (cm), hip circumference/HC (cm), height (inches), weight (kg), waist hip ratio/WHR, body mass index/BMI and blood pressure. Laboratory investigations included fasting blood samples for glucose and lipids; including total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c) and triglycerides (TG). Calculations for TG/HDL ratio and TC/HDL ratio were made. Results: Metabolic syndrome (MS) was present in 26 (13.5%) individuals. Male to female ratio was 3:1. Values of waist circumference, blood pressure, fasting plasma glucose, triglyceride and HDL-c, were all high. On comparison of fasting lipid profile, TC/HDL ratio and TG/HDL ratio, it was observed that the average total cholesterol, HDL cholesterol, TCL/HDL ratio were insignificant. The average triglyceride level and TG/HDL ratio were all high. The ROC curve for total cholesterol, HDL-c, TG, TC/HDL and TG/HDL ratio yielded 0.555, 0.526, 0.912, 0.548 and 0.913 areas under the curve. Plasma TG, TG/HDL ratio produced significant p-values < 0.001. Abnormal triglycerides and TG/HDL ratio at a cutoff of 3.98 was diagnosed with high sensitivity and specificity. Conclusion: Fasting triglyceride and HDL-c play a major role in the pathogenesis of MS at an early age. Triglyceride level and TG/HDL ratio as opposed to HDL-c and TC/HDL-c clearly define the risk for development of atheroma formation in our adolescent

  9. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1981-01-01

    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  10. Leptin receptor and ghrelin genes polymorphisms in relation to the metabolism of lipids

    Directory of Open Access Journals (Sweden)

    Anna Trakovická

    2015-10-01

    Full Text Available The aim of this work was to analyse genetic polymorphisms in genes encoding leptin receptor (LEPR and ghrelin (GHR as genetic markers of metabolic disorders in human nutrition. Genomic DNA was obtained from in total 84 human blood samples. Effect of analysed genetic markers was evaluated for three biochemical parameters: total cholesterol, HDL and LDL cholesterol. The PCR-RFLP method was used for identification of SNPs in LEPR (Gln223Arg and GHR (171T/C genes. In analysed population prevalence of heterozygous LEPRAG (47.62% and GHRCT (40.48% genotypes was observed. Frequency of LEPRA and LEPRB alleles were 0.55 and 0.45, respectively. Similar the GHRC allele had only slight predominance than GHRT allele (0.54/0.46. In population was found higher level of observed heterozygosity across loci (0.44. For both SNPs was found high effective allele number (1.98 which was also transferred to the median level of polymorphic information content (0.37. Association analysis of LEPR and GHR genotypes effect on selected biochemical parameters was performed using GLM procedure. Significant association was found only for levels of LDL cholesterol (P<0.01. Our study shows that both genes are involved in nutritional status and therefore can be considered as candidate genes of lipids metabolism disorders and obesity.

  11. Proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism, atherosclerosis and ischemic stroke.

    Science.gov (United States)

    Zhang, Lingling; Song, Kangping; Zhu, Mengting; Shi, Jinling; Zhang, Huijuan; Xu, Liang; Chen, Yingzhu

    2016-08-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the proprotein convertase family. It is an important regulator of cholesterol metabolism. PCSK9 can bind to low-density lipoprotein receptors (LDLRs) and induce the degradation of these receptors through the endosome/lysosome pathway, thus decreasing the LDLR levels on the cell surface of hepatocytes, resulting in increased serum low-density lipoprotein cholesterol (LDL-C) concentrations. Recent studies have found that gene polymorphisms of PCSK9 are associated with hypercholesterolemia, risk of atherosclerosis, and ischemic stroke. Furthermore, monoclonal antibodies, peptide mimetics, small molecule inhibitors and gene silencing agents that are associated with PCSK9 are some of the newer pharmaceutical therapeutic strategies and approaches for lowering serum LDL-C levels. In this review, we will discuss recent advances in PCSK9 research, which show that PCSK9 is correlated with lipid metabolism, atherosclerosis, and, in particular, ischemic stroke. We will also discuss the current state of PCSK9 therapeutics and their potential in modulating these diseases. PMID:26040332

  12. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    International Nuclear Information System (INIS)

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks

  13. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory, E-mail: Tory.Hagen@oregonstate.edu [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  14. Abnormalities in carbohydrate and lipid metabolisms in high-fructose dietfed insulin-resistant rats: amelioration by Catharanthus roseus treatments.

    Science.gov (United States)

    Rasineni, Karuna; Bellamkonda, Ramesh; Singareddy, Sreenivasa Reddy; Desireddy, Saralakumari

    2013-09-01

    High intake of dietary fructose has been shown to exert a number of adverse metabolic effects in humans and experimental animals. The present study was proposed to elucidate the effect of Catharanthus roseus (C. roseus) leaf powder treatment on alterations in carbohydrate and lipid metabolisms in rats fed with high-fructose diet. Male Wistar rats of body weight around 180 g were divided into four groups, two of these groups (groups C and C+CR) were fed with standard pellet diet and the other two groups (groups F and F+CR) were fed with high-fructose (66 %) diet. C. roseus leaf powder suspension in water (100 mg/kg body weight/day) was administered orally to group C+CR and group F+CR. At the end of a 60-day experimental period, biochemical parameters related to carbohydrate and lipid metabolisms were assayed. C. roseus treatment completely prevented the fructose-induced increased body weight, hyperglycemia, and hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F was significantly decreased with C. roseus treatment in group F+CR. The alterations observed in the activities of enzymes of carbohydrate and lipid metabolisms and contents of hepatic tissue lipids in group F rats were significantly restored to near normal values by C. roseus treatment in group F+CR. In conclusion, our study demonstrates that C. roseus treatment is effective in preventing fructose-induced insulin resistance and hypertriglyceridemia while attenuating the fructose-induced alterations in carbohydrate and lipid metabolisms. This study suggests that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it. PMID:23334857

  15. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA. PMID

  16. MicroRNA and lipid metabolism%微小RNA与脂质代谢

    Institute of Scientific and Technical Information of China (English)

    明月; 肖晓秋

    2012-01-01

    微小RNA(MicroRNA)是一类单链非编码小分子RNA,在进化上具有高度保守性.microRNA参与调控转录后水平的基因表达,通常与靶mRNA的3’非翻译区(Untranslated region,UTR)互补结合,抑制靶基因的表达.研究发现,microRNA与脂质代谢密切相关,其中,肝脏中含量最多的microRNA为miR-122,miR-122对于维持肝细胞的正常形态及功能有很重要的作用,miR-33在胞内胆固醇外排、脂肪酸β氧化和高密度脂蛋白代谢方面也发挥着很重要的作用.这些重要的研究结果表明,microRNA参与维持了脂质内稳态,有可能成为临床上治疗脂代谢紊乱的新途径.%MicroRNAs are small noncoding RNAs,single stranded in the mature form. microRNAs are post-transcriptional regulators that hind to complementary sequences on target mRNAs,usually resulting in translational repression or target degradation and gene silencing. Recent advances in the understanding of lipid metabolism have revealed that microRNAs play major roles in regulating cholesterol and fatty acid homeostasis. MiR-122,the most abundant microRNAs in the liver,is associated with cholesterol metabolism and hepatocellular carcinoma. MiR-33 regulates cholesterol efflux,fatty acid β oxidation,and high-density lipoprotein metabolism. These findings show that microRNAs play an important role in lipid homeostasis and potentially open new avenues for the treatment of dyslipidemias.

  17. PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

    Science.gov (United States)

    Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

    2014-04-01

    Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

  18. The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs

    DEFF Research Database (Denmark)

    Petersen, E.; Mu, Huiling; Porsgaard, Trine;

    2010-01-01

    Background: Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Gottingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to...... have similar reactions to antiretroviral drugs. Methods: The pigs were treated orally with high doses of the protease inhibitors ritonavir and saquinavir for 4 weeks. The model allows repeated concomitant biopsies from liver, muscle, adipose tissue and plasma samples. Results: The study showed a...... levels, suggesting a prolonged effect of the antiretroviral drug treatment lasting beyond the 4 week post-treatment observation period. Conclusions: The Gottingen mini-pig model is a promising animal model for rapid screening of the metabolic effects induced by antiretroviral drugs....

  19. Effect of waterborne zinc exposure on lipid deposition and metabolism in hepatopancreas and muscle of grass carp Ctenopharyngodon idella.

    Science.gov (United States)

    Hu, Wei; Mai, Kang-Sen; Luo, Zhi; Zheng, Jia-Lang; Huang, Chao; Pan, Ya-Xiong

    2016-08-01

    The aim of the present study was to explore the effect of waterborne zinc (control, 0.85, 2.20, 3.10 mg/l, respectively) exposure on lipid deposition and metabolism in the hepatopancreas and muscle of grass carp Ctenopharyngodon idella. The lipid content, Zn accumulation, and the activities and expression levels of several enzymes involved in lipid metabolism were determined in hepatopancreas and muscle. Waterborne Zn exposure reduced growth performance and increased Zn accumulation in both tested tissues. In hepatopancreas, Zn exposure increased lipid content, the activities of lipogenic enzymes, such as 6PGD, G6PD, ME, ICDH and FAS, as well as the mRNA expression level of G6PD, 6PGD, ICDH, FAS and SREBP-1. But the activity of CPT I and the mRNA expression of HSL, CPT Iα1a, CPT Iα2a and PPARα were down-regulated by Zn exposure. In contrast, in muscle, waterborne Zn exposure decreased lipid deposition, activities of 6GPD, ICDH and ME, as well as the mRNA expression level of G6PD, ICDH, ME, FAS and SREBP-1. However, the activity of CPT I as well as the mRNA expression level of PPARα, HSL, CPT Iα2a, CPT Iα1b and CPT Iβ were up-regulated by Zn exposure. Our results indicate that waterborne Zn increases lipid content by up-regulating lipogenesis and down-regulating lipolysis in hepatopancreas. But, in muscle, waterborne Zn reduces lipid accumulation by up-regulating lipolysis and down-regulating lipogenesis. Differential patterns of lipid deposition, enzymatic activities and genes' expression indicate the tissue-specific regulatory mechanism in fish. PMID:26820140

  20. Effects of physical training with different intensities of effort on lipid metabolism in rats submitted to the neonatal application of alloxan

    OpenAIRE

    Ribeiro Carla; Cambri Lucieli; Dalia Rodrigo; de Araújo Michel; Botezelli José; Sponton Amanda Christine; Mello Maria

    2012-01-01

    Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by insulin resistance. Its development is directly connected with the inability of insulin to exert its action, not just on carbohydrate metabolism but also on primarily on lipid metabolism. The present study aimed to compare the effects of continuous, intermittent, and strength training on serum and tissue variables on the lipid metabolism of alloxan rats. Methods Wistar rats were divided into eigh...

  1. Response of C2C12 Myoblasts to Hypoxia: The Relative Roles of Glucose and Oxygen in Adaptive Cellular Metabolism

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    Wei Li

    2013-01-01

    Full Text Available Background. Oxygen and glucose are two important nutrients for mammalian cell function. In this study, the effect of glucose and oxygen concentrations on C2C12 cellular metabolism was characterized with an emphasis on detecting whether cells show oxygen conformance (OC in response to hypoxia. Methods. After C2C12 cells being cultured in the levels of glucose at 0.6 mM (LG, 5.6 mM (MG, or 23.3 mM(HG under normoxic or hypoxic (1% oxygen condition, cellular oxygen consumption, glucose consumption, lactate production, and metabolic status were determined. Short-term oxygen consumption was measured with a novel oxygen biosensor technique. Longer-term measurements were performed with standard glucose, lactate, and cell metabolism assays. Results. It was found that oxygen depletion in normoxia is dependent on the glucose concentration in the medium. Cellular glucose uptake and lactate production increased significantly in hypoxia than those in normoxia. In hypoxia the cellular response to the level of glucose was different to that in normoxia. The metabolic activities decreased while glucose concentration increased in normoxia, while in hypoxia, metabolic activity was reduced in LG and MG, but unchanged in HG condition. The OC phenomenon was not observed in the present study. Conclusions. Our findings suggested that a combination of low oxygen and low glucose damages the viability of C2C12 cells more seriously than low oxygen alone. In addition, when there is sufficient glucose, C2C12 cells will respond to hypoxia by upregulating anaerobic respiration, as shown by lactate production.

  2. Metabolic regulation in meagre, Argyrosomus regius (Asso, 1801: Study of gene-diet interactions on lipid metabolism

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    Francisca Silva-Brito

    2014-06-01

    stimulates the expression of the fads2. In contrast, Elovl5 is very efficient to convert the desaturated products of ∆6/∆8 and so Elovl5 expression is not enhanced, since the activity of this enzyme is already higher. These findings may explain the differences in the expression of two genes, between hepatic fads2 and elovl5. Furthermore, increased hepatic fads2 expression between FO-S and VO-S treatments was 114 fold. Such induction was much greater than observed in Salmo salad (Zheng et al., 2005. However, Salmo salad has separate and distinct genes for ∆6 and ∆5 desaturases (Zheng et al., 2005 and, due to genome duplication, it has two genes with ∆6 activity (Monroig et al., 2010. Moreover, lipid peroxidation in liver increases with the number of fatty acid (FA double bonds (Haggag, Elsanhoty & Ramadan, 2014. D'Aquino et al. (1991 observed that rats fed diets with fish oil had increased lipid peroxidation. Our results indicate that, in FO-S, selenium may have protected FA from peroxidation, thus dietary HUFA seemed to have been sufficient to maintain the phospholipid turnover and induction of FA metabolism genes did not occur. In FO-NS diet membranes were not protected efficiently from lipid peroxidation, and therefore a higher expression of FA metabolism genes was necessary to offset the damage, consequently, biosynthesis of HUFA was more stimulated. ROS-induced oxidative stress has been associated with expression and protein levels of transcription factors (Okuno et al., 2012. A reduction of ROS (Reactive Oxygen Species has been observed in fish fed VO with selenium, when compared to VO without selenium (data not presented. It is plausible to infer that a stimulation of expression and level of protein SREBP-1 by a reduction of ROS. SREBP-1 play a role on the regulation of genes involved in biosynthesis of HUFA, as fads2 and elovl5 (Jump, Tripathy & Depner, 2013. In conclusion, our results showed that vegetable oils have an effect on expression level of genes

  3. Comparative Study of EPA-enriched Phosphatidylcholine and EPA-enriched Phosphatidylserine on Lipid Metabolism in Mice.

    Science.gov (United States)

    Ding, Lin; Wang, Dan; Zhou, Miaomiao; Du, Lei; Xu, Jie; Xue, Changhu; Wang, Yuming

    2016-07-01

    Recent studies have shown that EPA enriched PLs have beneficial effects on lipid metabolism. Our previous study has demonstrated that the anti-obesity and hypolipidemic effects of EPA-PL were superior to DHA-PL. In the present study, we comparatively evaluated the effects of EPA-enriched phosphatidylcholine (EPA-PC) and EPA-enriched phosphatidylserine (EPA-PS) on lipid metabolism in mice. Both 2% dietary EPA-PC and EPA-PS significantly improved serum and hepatic lipid levels in mice. The HDL-c level in mice on EPA-PC diet was significantly higher than the other two groups. The level of DHA in hepatic TG and PL were significantly increased in both EPA-PC and EPA-PS fed groups (98.3 and 117.8%, respectively; p DHA in EPA-PS group was significantly higher than the EPA-PC group. EPA-PC and EPA-PS suppressed hepatic SREBP-1c mediated lipogenesis and activated PPARα mediated fatty acid β-oxidation in the liver. These data are the first to indicate that EPA-PS has beneficial effects on lipid metabolism. PMID:27321119

  4. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

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    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There is a high prevalence of diabetes mellitus (DM and dyslipidemia in women with polycystic ovary syndrome (PCOS. The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C, n = 10; the andronate-treated group (Andronate, n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks; and the andronate-treated and high-fat diet group (Andronate+HFD, n = 10. The rate of glucose appearance (Ra of glucose, gluconeogenesis (GNG, and the rate of glycerol appearance (Ra of glycerol were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P P Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

  5. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice.

    Science.gov (United States)

    Georgiadis, Ioannis; Karatzas, Theodore; Korou, Laskarina-Maria; Agrogiannis, George; Vlachos, Ioannis S; Pantopoulou, Alkisti; Tzanetakou, Irene P; Katsilambros, Nikolaos; Perrea, Despina N

    2014-03-01

    Chios mastic gum (MG), a resin produced from Pistacia lentiscus var. Chia, is reported to possess beneficial cardiovascular and hepatoprotective properties. This study investigated the effect of crude Chios MG on metabolic parameters in diabetic mice. Streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were assigned to three groups: NC (n=9) control; LdM (n=9) animals receiving low dose mastic for 8 weeks (20 mg/kg body weight [BW]); and HdM (n=9) animals receiving high dose mastic (500 mg/kg BW) for the same period. Serum lipid and glucose levels were determined at baseline, at 4 and 8 weeks. Serum total protein, adiponectin, and resistin levels were also measured at the end of the experiment. Histopathological examination for liver, kidney, aorta, and heart lesions was performed. After 4 weeks, MG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM, whereas BW levels were reduced in LdM group compared with controls. At the end of the experiment, LdM presented significantly lower serum glucose, cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improved high-density lipoprotein cholesterol levels compared with control group. HdM group had ameliorated serum triglyceride levels. Hepatic steatosis observed in control group was partially reversed in LdM and HdM groups. MG administered in low dosages improves glucose and lipid disturbances in diabetic mice while alleviating hepatic damage. PMID:24404977

  6. Comprehensive Analysis of PPARα-Dependent Regulation of Hepatic Lipid Metabolism by Expression Profiling

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    Maryam Rakhshandehroo

    2007-09-01

    Full Text Available 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 overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip, electron-transferring-flavoprotein β polypeptide (Etfb, electron-transferring-flavoprotein dehydrogenase (Etfdh, phosphatidylcholine transfer protein (Pctp, endothelial lipase (EL, Lipg, adipose triglyceride lipase (Pnpla2, hormone-sensitive lipase (HSL, Lipe, and monoglyceride lipase (Mgll. Using an in silico screening approach, one or more PPAR response elements (PPREs were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARα agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver.

  7. Exploration of lipid metabolism in relation with plasma membrane properties of Duchenne muscular dystrophy cells: influence of L-carnitine.

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    Françoise Le Borgne

    Full Text Available Duchenne muscular dystrophy (DMD arises as a consequence of mutations in the dystrophin gene. Dystrophin is a membrane-spanning protein that connects the cytoskeleton and the basal lamina. The most distinctive features of DMD are a progressive muscular dystrophy, a myofiber degeneration with fibrosis and metabolic alterations such as fatty infiltration, however, little is known on lipid metabolism changes arising in Duchenne patient cells. Our goal was to identify metabolic changes occurring in Duchenne patient cells especially in terms of L-carnitine homeostasis, fatty acid metabolism both at the mitochondrial and peroxisomal level and the consequences on the membrane structure and function. In this paper, we compared the structural and functional characteristics of DMD patient and control cells. Using radiolabeled L-carnitine, we found, in patient muscle cells, a marked decrease in the uptake and the intracellular level of L-carnitine. Associated with this change, a decrease in the mitochondrial metabolism can be seen from the analysis of mRNA encoding for mitochondrial proteins. Probably, associated with these changes in fatty acid metabolism, alterations in the lipid composition of the cells were identified: with an increase in poly unsaturated fatty acids and a decrease in medium chain fatty acids, mono unsaturated fatty acids and in cholesterol contents. Functionally, the membrane of cells lacking dystrophin appeared to be less fluid, as determined at 37°C by fluorescence anisotropy. These changes may, at least in part, be responsible for changes in the phospholipids and cholesterol profile in cell membranes and ultimately may reduce the fluidity of the membrane. A supplementation with L-carnitine partly restored the fatty acid profile by increasing saturated fatty acid content and decreasing the amounts of MUFA, PUFA, VLCFA. L-carnitine supplementation also restored muscle membrane fluidity. This suggests that regulating lipid metabolism

  8. Adaptation of chondrocytes to low oxygen tension: relationship between hypoxia and cellular metabolism.

    Science.gov (United States)

    Rajpurohit, R; Koch, C J; Tao, Z; Teixeira, C M; Shapiro, I M

    1996-08-01

    In endochondral bone, the growth cartilage is the site of rapid growth. Since the vascular supply to the cartilage is limited, it is widely assumed that cells of the cartilage are hypoxic and that limitations in the oxygen supply regulate the energetic state of the maturing cells. In this report, we evaluate the effects of oxygen tension on chondrocyte energy metabolism, thiol status, and expression of transcription elements, HIF and AP-1. Imposition of an hypoxic environment on cultured chondrocytes caused a proportional increase in glucose utilization and elevated levels of lactate synthesis. Although we observed a statistical increase in the activities of phosphofructokinase, pyruvate kinase, lactate dehydrogenase, and creatine kinase after exposure to lowered oxygen concentrations, the effect was small. The cultured cells exhibited a decreased utilization of glutamine, possibly due to down regulation of mitochondrial function and inhibition of oxidative deamination. With respect to total energy generation, we noted that these cells are quite capable of maintaining the energy charge of the cell at low oxygen tensions. Indeed, no changes in the absolute quantity of adenine nucleotides or the energy charge ratio was observed. Hypoxia caused a decrease in the glutathione content of cultured chondrocytes and a concomitant rise in cell and medium cysteine levels. It is likely that the fall in cell glutathione level is due to decreased synthesis of the tripeptide under reduced oxygen stress and the limited supply of glutamate. The observed rise in cellular and medium cysteine levels probably reflects an increase in the rate of degradation of glutathione and a decrease in synthesis of the peptide. To explore how cells transduce these metabolic effects, gel retardation assays were used to study chondrocyte HIF and AP-1 binding activities. Chondrocyte nuclear preparations bound an HIF-oligonucleotide; however, at low oxygen tensions, no increase in HIF binding was

  9. Dissecting lipid metabolism in meibomian glands of humans and mice: An integrative study reveals a network of metabolic reactions not duplicated in other tissues.

    Science.gov (United States)

    Butovich, Igor A; McMahon, Anne; Wojtowicz, Jadwiga C; Lin, Feng; Mancini, Ronald; Itani, Kamel

    2016-06-01

    Lipids comprise the bulk of the meibomian gland secretion (meibum) which is produced by meibocytes. Complex arrays of lipogenic reactions in meibomian glands, which we collectively call meibogenesis, have not been explored on a molecular level yet. Our goals were to elucidate the possible biosynthetic pathways that underlie the generation of meibum, reveal similarities in, and differences between, lipid metabolism in meibomian glands and other organs and tissues, and integrate meibomian gland studies into the field of general metabolomics. Specifically, we have conducted detailed analyses of human and mouse specimens using genomic, immunohistochemical, and lipidomic approaches. Among equally highly expressed genes found in meibomian glands of both species were those related to fatty acid elongation, branching, desaturation, esterification, reduction of fatty acids to alcohols, and cholesterol biosynthesis. Importantly, corresponding lipid products were detected in meibum of both species using lipidomic approaches. For the first time, a cohesive, unifying biosynthetic scheme that connects genomic, lipidomic, and immunohistochemical observations is outlined and discussed. PMID:27032494

  10. Subclinical hypocalcemia, plasma biochemical parameters, lipid metabolism, postpartum disease, and fertility in postparturient dairy cows.

    Science.gov (United States)

    Chamberlin, W G; Middleton, J R; Spain, J N; Johnson, G C; Ellersieck, M R; Pithua, P

    2013-01-01

    A study was conducted to evaluate the potential association between Ca status at calving and postpartum energy balance, liver lipid infiltration, disease occurrence, milk yield and quality parameters, and fertility in Holstein cows. One hundred cows were assigned to 1 of 2 groups based on whole-blood ionized Ca concentration ([iCa]) on the day of calving [d 0; hypocalcemic [iCa] Cows were blocked based on calving date and parity. Blood samples were collected approximately 14 d from expected calving date (d -14), the day of calving (d 0), and on d 3, 7, 14, 21, and 35 postpartum for measurement of plasma nonesterified fatty acid, iCa, total Ca, glucose, and total and direct bilirubin concentrations, and plasma aspartate aminotransferase and gamma glutamyl transferase activities. Liver biopsies were obtained from a subset of cows on d 0, 7, and 35 for quantification of lipid content. Milk samples were collected on d 3, 7, 14, 21, and 35 postpartum for measurement of somatic cell count and percentages of protein, fat, and solids-not-fat. Data for peak test-day milk yield, services per conception, and days open were obtained from Dairy Herd Improvement Association herd records. Disease occurrence was determined based on herd treatment records. Hypocalcemic cows had significantly higher nonesterified fatty acids on d 0. Hypocalcemic cows also had significantly more lipid in hepatocytes on d 7 and 35 postpartum. However, no statistically significant differences were observed between groups for plasma aspartate aminotransferase and gamma glutamyl transferase activities or total and direct bilirubin concentrations. Milk protein percentage was lower in hypocalcemic cows on d 21 and 35. However other milk quality variables (somatic cell count, milk fat percentage, and solids-not-fat) and milk yield variables (peak test-day milk yield and 305-d mature-equivalent 4% fat-corrected milk yield) did not differ between groups. No differences were observed between groups in the

  11. Chiglitazar, a novel PPARalpha/gamma dual agonists with beneficial effects on insulin resistance and lipid metabolism in MSG rats

    Institute of Scientific and Technical Information of China (English)

    Ping-pingLI; Yue-tengCHEN; QuanLIU; Su-juanSUN; Zhu-fangSHEN

    2004-01-01

    AIM: Peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma agonists lower lipid accumulation by different mechanisms. We investigated whether benefits could be achieved on insulin sensitivity and lipid metabolism by the dual PPARalpha/gamma agonist chiglitazar in MSG rats. METHODS: Chiglitazar was orally administered in 5, 10, 20 mg-kg-~.d~ dosages in MSG rats for 40 d. The drug therapeutic effect was evaluated by glucose tolerance tests, insulin tolerance tests, and hyperinsulinemic-euglycemic clamps technique. The level of

  12. Lipid droplets, lipophagy, and beyond.

    Science.gov (United States)

    Wang, Chao-Wen

    2016-08-01

    Lipids are essential components for life. Their various structural and physical properties influence diverse cellular processes and, thereby, human health. Lipids are not genetically encoded but are synthesized and modified by complex metabolic pathways, supplying energy, membranes, signaling molecules, and hormones to affect growth, physiology, and response to environmental insults. Lipid homeostasis is crucial, such that excess fatty acids (FAs) can be harmful to cells. To prevent such lipotoxicity, cells convert excess FAs into neutral lipids for storage in organelles called lipid droplets (LDs). These organelles do not simply manage lipid storage and metabolism but also are involved in protein quality management, pathogenesis, immune responses, and, potentially, neurodegeneration. In recent years, a major trend in LD biology has centered around the physiology of lipid mobilization via lipophagy of fat stored within LDs. This review summarizes key findings in LD biology and lipophagy, offering novel insights into this rapidly growing field. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26713677

  13. Modifications of the metabolic pathways of lipid and triacylglycerol production in microalgae

    Directory of Open Access Journals (Sweden)

    Yu Wei-Luen

    2011-11-01

    Full Text Available Abstract Microalgae have presented themselves as a strong candidate to replace diminishing oil reserves as a source of lipids for biofuels. Here we describe successful modifications of terrestrial plant lipid content which increase overall lipid production or shift the balance of lipid production towards lipid varieties more useful for biofuel production. Our discussion ranges from the biosynthetic pathways and rate limiting steps of triacylglycerol formation to enzymes required for the formation of triacylglycerol containing exotic lipids. Secondarily, we discuss techniques for genetic engineering and modification of various microalgae which can be combined with insights gained from research in higher plants to aid in the creation of production strains of microalgae.

  14. Metabolism of a lipid nanoemulsion resembling low-density lipoprotein in patients with grade III obesity

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    Simone Alves Dantas

    2010-01-01

    Full Text Available INTRODUCTION: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. OBJECTIVE: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. METHODS: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. RESULTS: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040, and the fractional clearance rate of cholesterol ester (h-1 was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971 in the controls. CONCLUSION: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

  15. Lipid metabolism enzyme ACSVL3 supports glioblastoma stem cell maintenance and tumorigenicity

    International Nuclear Information System (INIS)

    Targeting cell metabolism offers promising opportunities for the development of drugs to treat cancer. We previously found that the fatty acyl-CoA synthetase VL3 (ACSVL3) is elevated in malignant brain tumor tissues and involved in tumorigenesis. This study investigates the role of ACSVL3 in the maintenance of glioblastoma multiforme (GBM) stem cell self-renewal and the capacity of GBM stem cells to initiate tumor xenograft formation. We examined ACSVL3 expression during differentiation of several GBM stem cell enriched neurosphere cultures. To study the function of ACSVL3, we performed loss-of-function by using small interfering RNAs to target ACSVL3 and examined stem cell marker expression, neurosphere formation and tumor initiation properties. ACSVL3 expression levels were substantially increased in GBM stem cell enriched neurosphere cultures and decreased after differentiation of the neurospheres. Down-regulating ACSVL3 with small inhibiting RNAs decreased the expression of markers and regulators associated with stem cell self-renewal, including CD133, ALDH, Musashi-1 and Sox-2. ACSVL3 knockdown in neurosphere cells led to increased expression of differentiation markers GFAP and Tuj1. Furthermore, ACSVL3 knockdown reduced anchorage-independent neurosphere cell growth, neurosphere-forming capacity as well as self-renewal of these GBM stem cell enriched neurosphere cultures. In vivo studies revealed that ACSVL3 loss-of-function substantially inhibited the ability of neurosphere cells to propagate orthotopic tumor xenografts. A link between ACSVL3 and cancer stem cell phenotype was further established by the findings that ACSVL3 expression was regulated by receptor tyrosine kinase pathways that support GBM stem cell self-renewal and tumor initiation, including EGFR and HGF/c-Met pathways. Our findings indicate that the lipid metabolism enzyme ACSVL3 is involved in GBM stem cell maintenance and the tumor-initiating capacity of GBM stem cell enriched-neurospheres in

  16. The metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue

    Directory of Open Access Journals (Sweden)

    Buang Y

    2011-02-01

    Full Text Available Background: Di (2-ethyl hexyl phthalate is the most widely used  plasticizer in blood storage bag for transfusion. This substance can modify lipid metabolism. This study was aimed to elucidate the metabolic effects of di (2-ethyl hexyl phthalate medium dose on lipid profiles in serum and liver tissue.Methods: Sprague Dawley rats were fed 1.0 % di (2-ethyl hexyl phthalate diet (DEHP group, n=5 or a non-supplemented diet (control group, n=5 for 10 days. The rats were allowed to freely access each food. Serum lipid concentrations were measured using enzyme assay kits. Lipids of liver tissues were extracted and the lipid contents were determined. A peach of liver was prepared to determine the activities of malic enzyme and carnitine palmitoyl transferase-1 (CPT-1.Results: Serum lipid concentrations (mg/dL of DEHP group decreased compared to control (P<0.05. The serum triglyceride (TG concentrations of control and DEHP groups were respectively (100.5±16.5 and (31.2±1.7; phospholipid (PL, (143.3±7.8 and (88.9±3.2; total cholesterol, (88.7±4.6 and (51.9±2.3. The liver TG content of control and DEHP group (mg/g liver were respectively, (40.8±4.4 and (23.7±1.3; liver cholesterol were (3.36±0.29 and (2.33±0.23; and the liver PL were (36.5±1.0 and (41.7±0.6. Malic enzyme and CPT-1 activities (nmol/min/mg protein of DEHP group increased compared to control (P<0.05, in which their increases were approximately by 4.35- and 2.33-folds,  respectively.Conclusion: The di (2-ethyl hexyl phthalate medium dose attenuates lipids secretion from the liver cells into the bloodstream. The increase of liver PL level accompanied with the promotions of malic enzyme and the CPT-1 activities are the key factors of the dietary di (2-ethyl hexyl phthalate effects in rats to attenuate the lipid secretions from the livers. (Med J Indones 2011; 20:20-6Keywords: Di (2-ethyl hexyl phthalate, hyperphospholipids, lipolysis, liver lipids, serum lipids

  17. Beneifcial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Rui Guo; Emily C Liong; Kwok Fai So; Man-Lung Fung; George L Tipoe

    2015-01-01

    BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneifcial effects of aerobic exercise on NAFLD. DATA SOURCE:We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. RESULTS:The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing in-trahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptorγ expression levels; (ii) decreas-ing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inlfammation via the inhibition of pro-inlfammatory media-tors such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. CONCLUSION:Aerobic exercise, via different mechanisms, signiifcantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

  18. Impact of micronized starfruit (Averrhoa carambola L.) fiber concentrate on lipid metabolism in mice.

    Science.gov (United States)

    Herman-Lara, Erasmo; Elvira-Torales, Laura I; Rodriguez-Miranda, Jesús; Torruco-Uco, Juan G; Carmona-García, Roselis; Mendoza-García, Patricia G; García, Hugo S; Soto-Rodríguez, Ida; Sánchez-Valdivieso, Enrique; Martínez-Sánchez, Cecilia E

    2014-11-01

    The objective of this study was to evaluate the effect of micronized insoluble fiber from starfruit bagasse as an ingredient of a functional food (FF) or as micronized insoluble fiber-rich fraction (IFRF) and its effects in vivo on lipids metabolism in a murine model. Experimental animals were divided in four isoproteic (15.8%) treatments differing on the fiber and cholesterol level used. The micronized IFRF particle size ranged from 37.5 to 149 μm. Treatments with added IFRF and those including the FF lowered serum triacylglycerols, total cholesterol (TC), high-density lipoproteins (HDL), and low-density lipoproteins (LDL) concentrations (IFRF: 14.2, 25.4, 55.06, and 12.18%, respectively; FF: 30.18, 39.47, 35.11, and 43.18%, respectively). IFRF produced the overall highest serum hypolipidemic effect and prevented the development of non-alcoholic fatty liver. Both the IFRF and the FF exhibited hypolipidemic effects that suggest a potential role of starfruit insoluble fiber as a component of FFs aimed against cardiovascular diseases. PMID:24846002

  19. Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Hyun [Department of Biological Sciences, Sookmyung Women’s University, Seoul (Korea, Republic of); Department of Biology, Chungnam National University, Daejeon (Korea, Republic of); So, Ju-Hoon; Kim, Hyun-Taek; Choi, Jung-Hwa; Lee, Mi-Sun [Department of Biology, Chungnam National University, Daejeon (Korea, Republic of); Choi, Seok-Yong [Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of); School of Biological Sciences and Technology, Chonnam National University, Gwangju (Korea, Republic of); Kim, Cheol-Hee, E-mail: zebrakim@cnu.ac.kr [Department of Biology, Chungnam National University, Daejeon (Korea, Republic of); Kim, Min Jung, E-mail: minkim@sookmyung.ac.kr [Department of Biological Sciences, Sookmyung Women’s University, Seoul (Korea, Republic of)

    2014-04-18

    Highlights: • angptl3 is specifically expressed in the liver of developing zebrafish. • Knockdown of Angptl3 decreases liver size in developing zebrafish. • Knockdown of zebrafish Angptl3 elicits a hypocholesterolemia phenotype. - Abstract: Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2.

  20. Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish

    International Nuclear Information System (INIS)

    Highlights: • angptl3 is specifically expressed in the liver of developing zebrafish. • Knockdown of Angptl3 decreases liver size in developing zebrafish. • Knockdown of zebrafish Angptl3 elicits a hypocholesterolemia phenotype. - Abstract: Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2

  1. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    Science.gov (United States)

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  2. Characterization of lipid metabolism in insulin-sensitive adipocytes differentiated from immortalized human mesenchymal stem cells

    International Nuclear Information System (INIS)

    There is a great demand for cell models to study human adipocyte function. Here we describe the adipogenic differentiation of a telomerase-immortalized human mesenchymal stem cell line (hMSC-Tert) that maintains numerous features of terminally differentiated adipocytes even after prolonged withdrawal of the peroxisome proliferator activated receptor γ (PPARγ) agonist rosiglitazone. Differentiated hMSC-Tert developed the characteristic monolocular phenotype of mature adipocytes. The expression of adipocyte specific markers was highly increased during differentiation. Most importantly, the presence of the PPARγ agonist rosiglitazone was not required for the stable expression of lipoprotein lipase, adipocyte fatty acid binding protein and perilipin on mRNA and protein levels. Adiponectin expression was post-transcriptionally down-regulated in the absence of rosiglitazone. Insulin sensitivity as measured by insulin-induced phosphorylation of Akt and S6 ribosomal protein was also independent of rosiglitazone. In addition to commonly used adipogenic markers, we investigated further PPARγ-stimulated proteins with a role in lipid metabolism. We observed an increase of lipoprotein receptor (VLDLR, LRP1) and apolipoprotein E expression during differentiation. Despite this increased expression, the receptor-mediated endocytosis of lipoproteins was decreased in differentiated adipocytes, suggesting that these proteins may have an additional function in adipose tissue beyond lipoprotein uptake

  3. Cardiovascular Risks Factors and their Relationship with Disorders of Carbohydrate and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Lilian Leguen Gulgar

    2014-12-01

    Full Text Available Background: cardiovascular disease has been the leading cause of death in Cuba, where studies on emerging cardiovascular risk factors as predictors of cardiovascular risk are scarce. Objective: to determine the association between cardiovascular risk factors and disorders of carbohydrate and lipid metabolism. Methods: a correlational study was conducted with a sample of 105 men and women selected from a total of 346 workers of the University of Medical Sciences of Cienfuegos from June 2011 through July 2012. The variables analyzed were age, sex, blood pressure, waist circumference, tobacco use, fasting blood glucose, triglycerides, cholesterol, HDL cholesterol, apolipoprotein A and B, TC/HDL ratio and apo B/apo AI ratio. Results: women older than 45 years had a higher prevalence of elevated waist circumference (60.0 %, hypertension (46.7 % and type 2 diabetes mellitus (54.3 % with hypertriglyceridemia (43.3 %, low HDLc levels (36.7 % and were 2.8 times more likely to develop elevated waist circumference; 66.7 % of the diabetic patients had low HDLc levels, 33.3 % developed hypertriglyceridemia and 66.7 % had a high total cholesterol/HDL cholesterol ratio. Conclusions: an association between age older than 45 years, female sex, obesity, hypertension and type 2 diabetes mellitus was observed. There was a higher prevalence of hypertriglyceridemia and low HDL cholesterol levels in obese and diabetic patients. Increased risk of low HDL cholesterol and high total cholesterol / HDL cholesterol ratio were also found.

  4. Effect of the daily consumption of ostrich and bovine meat on the lipid metabolism in rats

    Directory of Open Access Journals (Sweden)

    Edvaldo Vasconcelos de Carvalho-Filho

    2011-03-01

    Full Text Available The objective of this study is to evaluate the effect of the daily consumption of ostrich meat (lliofemuralis internus and bovine meat (Psoas major on the lipid metabolism in adult mice. The analyses of the centesimal composition of the meats and preparation of the diets were accomplished following the recommendations of the American Institute of Nutrition-AIN-93. Three groups of 150 day-old animals: group I (diet I, with casein, group II (diet II, with ostrich meat, and group III (diet III with bovine meat were fed for 13 weeks with the respective diets and weight gain, food efficiency coefficient, total cholesterol, lipoprotein fractions, hepatic, transaminases and body fat percentage and hepatic fat content were evaluated. No difference (p < 0.05 it was found for weight gain and coefficients for feed efficiency among the groups. Total cholesterol, HDL-cholesterol, LDL-cholesterol, relationship of total cholesterol/HDL-cholesterol, VLDL, triglycerides and hepatic transaminases were also not different among the groups (p < 0.05. This research suggests that the consumption of ostrich meat or thin bovine meat on a daily basis does not raise concerns about weight gain, and an increase in the plasma concentrations of lipoprotein and levels of hepatic transaminase.

  5. PPARγ Expression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

    Directory of Open Access Journals (Sweden)

    Patricia E. Almeida

    2012-01-01

    Full Text Available Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγ in favoring the establishment of chronic infection. Collectively, PPARγ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies.

  6. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage.

    Science.gov (United States)

    Raz, Itamar; Eldor, Roi; Cernea, Simona; Shafrir, Eleazar

    2005-01-01

    We present multiple findings on derangements in lipid metabolism in type 2 diabetes. The increase in the intracellular deposition of triglycerides (TG) in muscles, liver and pancreas in subjects prone to diabetes is well documented and demonstrated to attenuate glucose metabolism by interfering with insulin signaling and insulin secretion. The obesity often associated with type 2 diabetes is mainly central, resulting in the overload of abdominal adipocytes with TG and reducing fat depot capacity to protect other tissues from utilizing a large proportion of dietary fat. In contrast to subcutaneous adipocytes, the central adipocytes exhibit a high rate of basal lipolysis and are highly sensitive to fat mobilizing hormones, but respond poorly to lipolysis restraining insulin. The enlarged visceral adipocytes are flooding the portal circulation with free fatty acids (FFA) at metabolically inappropriate time, when FFA should be oxidized, thus exposing nonadipose tissues to fat excess. This leads to ectopic TG accumulation in muscles, liver and pancreatic beta-cells, resulting in insulin resistance and beta-cell dysfunction. This situation, based on a large number of observations in humans and experimental animals, confirms that peripheral adipose tissue is closely regulated, performing a vital role of buffering fluxes of FFA in the circulation. The central adipose tissues tend to upset this balance by releasing large amounts of FFA. To reduce the excessive fat outflow from the abdominal depots and prevent the ectopic fat deposition it is important to decrease the volume of central fat stores or increase the peripheral fat stores. One possibility is to downregulate the activity of lipoprotein lipase, which is overexpressed in abdominal relatively to subcutaneous fat stores. This can be achieved by gastrointestinal bypass or gastroplasty, which decrease dietary fat absorption, or by direct means that include surgical removal of mesenteric fat. Indirect treatment consists

  7. Influence of nitrogen status and light / dark cycle on Isochrysis sp. (Haptophyceae) lipid metabolism

    OpenAIRE

    Lacour, Thomas

    2010-01-01

    This thesis presents various cases of acclimation of a phytoplankton species (Isochrysis sp.) to changes in growth conditions, with special emphasis on the lipid response to those changes. In this context we have studied lipids as both products (triacylglycerol) and actors (glycolipids) of photosynthesis. First, we studied the influence of several types of nitrogen limitation on the neutral lipid content of algae. We showed that the relationship between nitrogen availability and lipid content...

  8. Sugar-Sweetened Beverage Consumption Is Associated with Metabolic Syndrome in Iranian Adults: Tehran Lipid and Glucose Study

    OpenAIRE

    Ejtahed, Hanieh-Sadat; Bahadoran, Zahra; Mirmiran, Parvin; Azizi, Fereidoun

    2015-01-01

    Background Metabolic syndrome (MetS), a cluster of multiple metabolic abnormalities, is one of the major public health challenges worldwide. The current study was conducted to evaluate the association between sugar-sweetened beverage (SSB) consumption and MetS and its components in Iranian adults. Methods This cross-sectional study was conducted among 5,852 men and women, aged 19 to 70 years, who participated in the fourth phase (2009 to 2011) of the Tehran Lipid and Glucose Study. Demographi...

  9. Risk factors of disturbances in carbohydrate and lipid metabolism and some pleiotropic effects of antihypertensive therapy in pregnant women

    Directory of Open Access Journals (Sweden)

    A V Padyganova

    2013-03-01

    Full Text Available The any kind of hypertension developing during the pregnancy, associated with high cardiovascular risk in the future. At the pregnancy complicated by development by arterial hypertension, there are more expressed changes of a carbohydrate and lipide metabolism, than it is peculiar to normally proceeding pregnancy, were by important pathogenetic links of obesity, diabetes, cardiovascular complications. Identification of new mechanisms of action of antihypertensive means associated with positive influences on exchange processes, is represented very demanded, considering pandemic nature of prevalence of metabolic violations in modern population.

  10. Performance, carcass characteristics, and lipid metabolism in growing and finishing Simmental steers fed varying concentrations of copper.

    Science.gov (United States)

    Engle, T E; Spears, J W

    2001-11-01

    An experiment was conducted to determine the effects of dietary copper (Cu) on performance, carcass characteristics, and lipid metabolism in Simmental steers. Thirty-six Simmental steers (329.3 +/-11.4 kg) were stratified by weight and randomly assigned to treatments. Treatments consisted of the following: control (no supplemental Cu) and 10 or 40 mg Cu/kg DM from Cu sulfate. Each treatment consisted of six replicate pens, with each pen containing two steers. A corn silage-soybean meal-based diet was fed for 56 d. Steers were then switched to a high concentrate diet. Performance was not affected by treatment during the growing or finishing phases. Plasma Cu concentrations were higher (P Simmental steers increased Cu status but had no effect on performance, carcass characteristics, or lipid or cholesterol metabolism. PMID:11768123

  11. Effect of randomization of mixtures of butter oil and vegetable oil on absorption and lipid metabolism in rats

    DEFF Research Database (Denmark)

    Becker, C.; Lund, Pia; Hølmer, Gunhild Kofoed

    2001-01-01

    dietary fats compared. Data on the fate of such lipids beyond the bloodstream is rather scarce and animal model studies are needed. Aim of the study To compare the metabolism of butter oil and mixtures of butter and rapeseed oil, native or randomized, in a model. The regiospecific fatty acid distribution...... present in dietary fats was followed through absorption, chylomicron formation, and deposition in adipose tissue and in different liver lipids (triacylglycerols, phospholipids, and cholesterol esters). Methods Rats were fed for 6 weeks from weaning either butter oil (BO), a butteroil- rapeseed oil mixture...... 65:35 w/w (BR) or a randomized mixture of BR (tBR). Half of the animals were used for organ analysis, the rest for a postprandial study with the same fats and isolation of chylomicrons. The regiospecific distribution of the fatty acids present in the dietary fats was followed during metabolism by...

  12. Effect of probucol on reproductive performance, egg yolk cholesterol content, and lipid metabolism in the laying hen.

    Science.gov (United States)

    Naber, E C; Elliot, J F; Smith, T L

    1982-06-01

    Egg production type chickens were given the drug Probucol in their diets to determine its effect on egg production characteristics, liver lipid metabolism, egg yolk lipid synthesis, and egg yolk cholesterol concentration. In none of the three trials conducted did Probucol feeding affect egg production or body weight. The drug reduced total liver lipogenesis as measured by incorporation of 14C-acetate by surviving liver slices. Relative incorporation of 14C-acetate into cholesterol by liver was increased by the drug. However, in ovo incorporation of 14C-acetate in total yolk lipids remains unchanged and relative incorporation into yolk cholesterol is reduced. As a result, egg yolk cholesterol content is reduced by 5% with the .10% dietary level of drug administration. PMID:7111129

  13. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice.

    Science.gov (United States)

    Zhang, Xin-Ru; Fu, Xiu-Juan; Zhu, Da-Sheng; Zhang, Chao-Zai; Hou, Shi; Li, Min; Yang, Xiao-Hong

    2016-05-15

    Salidroside is known for its pharmacological properties and in particular its antioxidation effects. In recent years, it has been recognized that salidroside plays an important role in treating diabetes. Accumulated evidence suggests that microRNAs may be involved in diabetic lipid disorders. We investigated how salidroside regulates lipid metabolism through miR-370 in vivo and in vitro. After 4 weeks of a high-fat diet, and intraperitoneal injection of streptozotocin (100mg/kg), type 2 diabetes was induced in male C56BL/6J mice. After 4 weeks, mice with fasting blood glucose levels above 7.8mmol/l were divided into five groups: those with diabetes mellitus, and those treated with 40mg/kg, 80mg/kg, and 160mg/kg salidroside, and metformin (480mg/kg), for a further 4 weeks. The hypoglycemic effects of salidroside were consistently demonstrated when measuring fasting blood glucose levels, observing insulin-sensitizing effects, and testing oral glucose tolerance. In addition to this, the expressions of miR-370, and related lipid protein expression in primary hepatocytes, were examined in primary type 2 diabetic mice. The present study has shown that the expression levels of miR-370, SREBP-1 and FAS-1 were significantly elevated in the liver of type 2 diabetic mice. In contrast, the elevated expression levels were reversed by salidroside. The addition of salidroside attenuated the effect of miR-370, and reduced the expression of these lipid metabolism proteins in primary hepatocytes. These findings demonstrate that salidroside can directly decrease the expression of miR-370 in type 2 diabetic mice, and particularly in primary hepatocytes, affecting lipid metabolism in the liver. PMID:26948318

  14. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

    Science.gov (United States)

    K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV. PMID:27207037

  15. Neonatal Exposure to Parathion Alters Lipid Metabolism in Adulthood: Interactions with Dietary Fat Intake and Implications for Neurodevelopmental Deficits

    OpenAIRE

    Lassiter, T. Leon; Ryde, Ian T.; Levin, Edward D.; Seidler, Frederic J; Slotkin, Theodore A.

    2010-01-01

    Organophosphates are developmental neurotoxicants but recent evidence also points to metabolic dysfunction. We determined whether neonatal parathion exposure in rats has long-term effects on regulation of adipokines and lipid peroxidation. We also assessed the interaction of these effects with increased fat intake. Rats were given parathion on postnatal days 1–4 using doses (0.1 or 0.2 mg/kg/day) that straddle the threshold for barely detectable cholinesterase inhibition and the first signs o...

  16. Low-calorie Cranberry Juice Decreases Lipid Oxidation and Increases Plasma Antioxidant Capacity in Women with Metabolic Syndrome

    OpenAIRE

    Basu, Arpita; Betts, Nancy M.; Ortiz, Jennifer; Simmons, Brandi; Wu, Mingyuan; Lyons, Timothy J.

    2011-01-01

    Cranberries, high in polyphenols have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low calorie cranberry juice (Ocean Spray Cranberries, Inc. MA, USA) will decrease surrogate risk factors of cardiovascular disease (CVD), such as, lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized double-blind pla...

  17. Hydrocortisone stimulates the development of oligodendrocytes in primary glial cultures and affects glucose metabolism and lipid synthesis in these cultures

    OpenAIRE

    Warringa, R.A.J.; Hoeben, R C; Koper, W.J.; Sykes, J.E.C.; Golde, L.M.G. van; Lopes-Cardozo, M.

    1987-01-01

    Cultures of glial cells were prepared from the brains of one-week-old rat pups. After one day in culture, serum was omitted from the medium and replaced by a combination of growth-stimulating hormones and other factors that enhanced the percentage of oligodendrocytes in the cultures. We investigated the effects of hydrocortisone on the development of oligodendrocytes, on the activities of oligodendrocyte-specific enzymes and on glucose- and lipid-metabolism of the glial cells. (1) Hydrocortis...

  18. Comparison of ruminal lipid metabolism in dairy cows and goats fed diets supplemented with starch, plant oil, or fish oil

    OpenAIRE

    Gutierrez Toral, Pablo; Bernard, Laurence; Belenguer, A.; Rouel, Jacques; Hervás, G.; Chilliard, Yves; Frutos, P.

    2016-01-01

    Direct comparison of cow and goat performance and milk fatty acid responses to diets known to induce milk fat depression (MFD) in the bovine reveals relevant species-by-diet interactions in ruminal lipid metabolism. Thus, this study was conducted to infer potential mechanisms responsible for differences in the rumen microbial biohydrogenation (BH) due to diet and ruminant species. To meet this objective, 12 cows and 15 goats were fed a basal diet (control), a similar diet supplemented with 2....

  19. Effects of Encapsulated Propolis on Blood Glycemic Control, Lipid Metabolism, and Insulin Resistance in Type 2 Diabetes Mellitus Rats

    OpenAIRE

    Yajing Li; Minli Chen; Hongzhuan Xuan; Fuliang Hu

    2012-01-01

    The present study investigates the encapsulated propolis on blood glycemic control, lipid metabolism, and insulin resistance in type 2 diabetes mellitus (T2DM) rats. The animal characteristics and biological assays of body weight, fasting blood glucose (FBG), fasting serum insulin (FINS), insulin act index (IAI), triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured and euglycemic hyperinsulinemi...

  20. Preventive effects of metallothionein against DNA and lipid metabolic damages in dyslipidemic mice under repeated mild stress

    OpenAIRE

    Higashimoto, Minoru; Isoyama, Naohiro; Ishibashi, Satoshi; Ogawa, Naoko; Takiguchi, Masufumi; Suzuki, Shinya; Ohnishi, Yoshinari; Sato, Masao

    2013-01-01

    The effects of repeated mild stress on DNA and lipid metabolic damages in multiple organs of dyslipidemic mice, and the preventive role of metallothionein (MT) were investigated. Female adult wild-type and MT-null mice fed high-fat diet (HFD) or standard diet (STD) were repeatedly subjected to fasting or restraint for three weeks. The liver, pancreas, spleen, bone marrow and serum samples were taken for evaluating DNA damage, MT, glutathione (GSH), corticosterone, carnitine and adiponectin. B...

  1. The eSS rat, a nonobese model of disordered glucose and lipid metabolism and fatty liver

    OpenAIRE

    Daniele Stella M; Montenegro Silvana M.; Tarres María C; Picena Juan C; Martinez Stella M

    2010-01-01

    Abstract Background eSS is a rat model of type 2 diabetes characterized by fasting hyperglycemia, glucose intolerance, hyperinsulinemia and early hypertriglyceridemia. Diabetic symptoms worsen during the second year of life as insulin release decreases. In 12-month-old males a diffuse hepatic steatosis was detected. We report the disturbances of lipid metabolism of the model with regard to the diabetic syndrome. Methods The study was conducted in eight 12-month-old eSS male rats and seven age...

  2. Conjugated linoleic acid intake in humans: a systematic review focusing on its effect on body composition, glucose, and lipid metabolism.

    Science.gov (United States)

    Salas-Salvadó, J; Márquez-Sandoval, F; Bulló, M

    2006-01-01

    Studies performed on different species show that the consumption of conjugated linoleic acid (CLA) leads to a loss of fat and total body weight, reduces the plasma concentrations of total and LDL cholesterol, and has an antiinflammatory effect. This article reviews the clinical trials on human beings that evaluate how mixtures of CLA isomers administered as supplements or CLA-enriched products can affect total body weight, body composition, plasma lipid profile, glycemia, insulinemia, insulin sensitivity, lipid oxidation, and inflammation. After analyzing the few studies published to date in reduced samples of healthy humans or patients with overweight, obesity, metabolic syndrome, or diabetes, we deduce that there is not enough evidence to show that conjugated linoleic acid has an effect on weight and body composition in humans. However, some of these studies have observed that the administration of various CLA isomers has adverse effects on lipid profile (it decreases HDL cholesterol concentration and increases Lp(a) circulating levels), glucose metabolism (glycemia, insulinemia or insulin sensitivity), lipid oxidation, inflammation, or endothelial function. Therefore, long-term randomized clinical trials, controlled with placebo, need to be made in large samples of patients to evaluate the efficacy and safety of CLA isomers before its indiscriminate use in human beings can be recommended. PMID:16864141

  3. Isolation and Expression Analysis of STAT Members from Synechogobius hasta and Their Roles in Leptin Affecting Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Kun Wu

    2016-03-01

    Full Text Available Signal transducers and activators of transcription proteins (STATs act as important mediators in multiple biological processes induced by a large number of cytokines. In the present study, full-length cDNA sequences of seven STAT members, including some splicing variants different from those in mammals, were obtained from Synechogobius hasta. The phylogenetic analysis revealed that the seven STAT members were derived from paralogous genes that might have arisen by whole genome duplication (WGD events during vertebrate evolution. All of these members share similar domain structure compared with those of mammals, and were widely expressed across the tested tissues (brain, gill, heart, intestine, liver, muscle and spleen, but at variable levels. Incubation in vitro of recombinant human leptin changed the intracellular triglyceride (TG content and mRNA levels of several STATs members, as well as expressions and activities of genes involved in lipid metabolism. Furthermore, Tyrphostin B42 (AG490, a specific inhibitor of the Janus Kinase 2(JAK2-STAT pathway, partially reversed leptin-induced change on STAT3 and its two spliced isoforms expression, as well as expressions and activities of genes involved in lipid metabolism. As a consequence, the decrease of TG content was also reversed. Thus, our study suggests that STAT3 is the requisite for the leptin signal and the activation of the STAT3 member may account for the leptin-induced changes in lipid metabolism in S. hasta.

  4. Liver X receptor antagonist reduces lipid formation and increases glucose metabolism in myotubes from lean, obese and type 2 diabetic individuals

    DEFF Research Database (Denmark)

    Kase, E T; Thoresen, G H; Westerlund, S; Højlund, Kurt; Rustan, A C; Gaster, M

    2007-01-01

    the synthetic agonist T0901317 on lipid and glucose metabolism in human skeletal muscle cells (myotubes). METHODS: Myotubes established from lean and obese control volunteers and from obese type 2 diabetic volunteers were treated with LXR ligands for 4 days. Lipid and glucose metabolisms were studied...... with labelled precursors, and gene expression was analysed using real-time PCR. RESULTS: Treatment with T0901317 increased lipogenesis (de novo lipid synthesis) and lipid accumulation in myotubes, this increase being more pronounced in myotubes from type 2 diabetic volunteers than from lean volunteers......AIMS/HYPOTHESIS: Liver X receptors (LXRs) play important roles in lipid and carbohydrate metabolism. The purpose of the present study was to evaluate effects of the endogenous LXR agonist 22-R-hydroxycholesterol (22-R-HC) and its stereoisomer 22-S-hydroxycholesterol (22-S-HC), in comparison with...

  5. Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis

    Science.gov (United States)

    Wang, Hai; Zhao, Miaoyun; Sud, Neetu; Christian, Patricia; Shen, Jing; Song, Yongyan; Pashaj, Anjeza; Zhang, Kezhong; Carr, Timothy; Su, Qiaozhu

    2016-01-01

    Insulin induced gene-2 (Insig-2) is an ER-resident protein that inhibits the activation of sterol regulatory element-binding proteins (SREBPs). However, cellular factors that regulate Insig-2 expression have not yet been identified. Here we reported that cyclic AMP-responsive element-binding protein H (CREBH) positively regulates mRNA and protein expression of a liver specific isoform of Insig-2, Insig-2a, which in turn hinders SREBP-1c activation and inhibits hepatic de novo lipogenesis. CREBH binds to the evolutionally conserved CRE-BP binding elements located in the enhancer region of Insig-2a and upregulates its mRNA and protein expression. Metabolic hormone glucagon and nutritional fasting activated CREBH, which upregulated expression of Insig-2a in hepatocytes and inhibited SREBP-1c activation. In contrast, genetic depletion of CREBH decreased Insig-2a expression, leading to the activation of SREBP-1c and its downstream lipogenic target enzymes. Compromising CREBH-Insig-2 signaling by siRNA interference against Insig-2 also disrupted the inhibitory effect of this signaling pathway on hepatic de novo triglyceride synthesis. These actions resulted in the accumulation of lipid droplets in hepatocytes and systemic hyperlipidemia. Our study identified CREBH as the first cellular protein that regulates Insig-2a expression. Glucagon activated the CREBH-Insig-2a signaling pathway to inhibit hepatic de novo lipogenesis and prevent the onset of hepatic steatosis and hypertriglyceridemia. PMID:27582413

  6. Impact of dietary protein on lipid metabolism-related gene expression in porcine adipose tissue

    Directory of Open Access Journals (Sweden)

    Ge Changrong

    2010-01-01

    Full Text Available Abstract Background High dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism. Methods Sixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18% or low protein (LP: 14% diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities. Results HP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC, fatty acid synthase (FAS and sterol regulatory element binding protein 1c (SREBP-1c at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL, carmitine palmtoyltransferase-1B (CPT-1B, peroxisome proliferator-activated receptor γ (PPARγ and adipocyte-fatty acid binding proteins (A-FABP at 60 kg, but reduced their expression at 100 kg. Gene expression and enzyme activity of hormone sensitive lipase (HSL was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPARγ in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg. Conclusion Fat deposition in Wujin

  7. Oligonol suppresses lipid accumulation and improves insulin resistance in a palmitate-induced in HepG2 hepatocytes as a cellular steatosis model

    OpenAIRE

    Park, Jae-Yeo; Kim, Younghwa; Im, Jee Ae; Lee, Hyangkyu

    2015-01-01

    Background Oligonol is a low molecular weight form of polyphenol polymers derived from lychee fruits. Several studies suggest that Oligonol has an anti-obesity effect. Since obesity is tightly associated with insulin resistance, we investigated a possible remission effect of Oligonol on lipid accumulation and insulin resistance in human hepatic HepG2 cells. Methods HepG2 cells were treated with palmitate for 24 h to induce cellular hepatic steatosis and insulin resistance. The cells were then...

  8. Activation of 5-[125I]iodonaphthyl-1-azide via excitation of fluorescent (N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)) lipid analogs in living cells. A potential tool for identification of compartment-specific proteins and proteins involved in intracellular transport and metabolism of lipids

    International Nuclear Information System (INIS)

    We describe a new technique for analysis of proteins located near fluorescent lipid analogs in intact living cells using the membrane-permeant, photoactivatable probe, 5-[125I]iodonaphthyl-1-azide ([125I]INA). [125I] INA can be activated directly with UV light or indirectly through excitation of adjacent fluorophores (photosensitizers) with visible light to modify nearby proteins covalently with 125I. In this report we demonstrate that fluorescent phospholipids and sphingolipids containing N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-6-aminocaproic acid serve as appropriate photosensitizers for [125I]INA. Using Chinese hamster ovary fibroblasts, we optimized the labeling conditions with respect to lipid concentration and time of irradiation and then examined the profiles of cellular proteins that were labeled when fluorescent analogs of ceramide, sphingomyelin, and phosphatidic acid were used as photosensitizers in living cells. The use of different fluorescent lipids, which label different subcellular compartments of cells as determined by fluorescence microscopy, derivatized different sets of cellular proteins with 125I. The labeled proteins were subsets of the total set of proteins available for derivatization as determined by direct activation of [125I]INA. Most proteins labeled by this procedure were pelleted by centrifugation of cell lysates at high speed (260,000 x g), but several soluble proteins were also labeled under these conditions. The implications of using this technique for identification of compartment-specific proteins and proteins involved in lipid metabolism and transport are discussed

  9. Computational Model of Cellular Metabolic Dynamics in Skeletal Muscle Fibers during Moderate Intensity Exercise

    OpenAIRE

    Li, Yanjun; Lai, Nicola; Kirwan, John P; Saidel, Gerald M.

    2012-01-01

    Human skeletal muscles have different fiber types with distinct metabolic functions and physiological properties. The quantitative metabolic responses of muscle fibers to exercise provide essential information for understanding and modifying the regulatory mechanisms of skeletal muscle. Since in vivo data from skeletal muscle during exercise is limited, a computational, physiologically based model has been developed to quantify the dynamic metabolic responses of many key chemical species. Thi...

  10. Effects of ozone exposure on lipid metabolism in human alveolar macrophages

    International Nuclear Information System (INIS)

    Alveolar macrophages (AM) store arachidonic acid (AA) which is esterified in cellular phospholipids until liberated by phospholipase A2 or C after exposure to inflammatory stimuli. Following release, there can be subsequent metabolism of AA into various potent, biological active mediators including prostaglandins and platelet activating factor (PAF). To examine the possibility that these mediators may account for some of the pathophysiologic alterations seen in the lung following O3 exposure, human AM were collected by bronchoalveolar lavage of normal subjects, plated into tissue culture dishes, and the adherent cells were incubated with 3H-AA or 3H-lysoPAF. Human AM exposed 1.0 ppm O3 for 2 hr released 65 + or - 12% more tritium, derived from 3H-AA, than paired air-exposed controls into media supernatants. In other studies using a similar O3 exposure protocol, there was also a significant increase in human AM PGE2 production (2.0 + or - 0.5 fold-increase above air-exposure values, p<0.01, n=17). In additional studies, using a similar O3 exposure protocol (1.0 ppm for 1 hr), there was also a significant increase in human AM PAF content (1.7 + or - 0.2 fold-increase above air-exposure values, p<0.02, n=5)

  11. Analysis of relationship between blood lipid metabolism levels and hs-CRP levels in patients with chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Objective: To study the relationship between blood lipid metabolism levels and hs-CRP levels in the patients with chronic obstructive pulmonary disease. Methods: The levels of plasma blood lipid (with biochemistry) and serum hs-CRP(with high-sensitive immuno turbidimetry) were determined in 96 patients with chronic obstructive pulmonary disease as well as 68 normal controls. Results: The plasma blood lipid levels in 96 patients with chronic obstructive pulmonary disease were significantly lower than those in 68 controls, plasma TC and LDL-C levels were not much difference (P>0.05), plasma HDL-C level was significantly difference (P<0.05), but TG and Lp (a) levels were very prominently difference (P<0.01). And the plasma hs-CRP level was significantly increased also (P<0.01). The close relationship was between blood lipid and hs-CRP levels. Conclusion: The study of relationship between blood lipid levels and hs-CRP levels in patients with COPD was helpful for understand the disease process as well as possible mechanisms. (authors)

  12. Postprandial metabolic changes in healthy males and in subjects homozygous for GWAS-identified variants at lipid metabolism loci

    OpenAIRE

    Brennauer, Tina

    2016-01-01

    The dissertation addresses the human metabolism after nutritional challenges in strictly controlled human intervention studies applying time-resolved plasma metabolomics measurements. The first part of the work aims to provide further insight into the postprandial metabolism by studies in healthy males. In the second part of the work metabolic challenge tests were applied to characterize the GWAS-identified gene variants rs2014355 in the acetyl-CoA-dehydrogenase short chain (ACADS) locus and ...

  13. Sex-specific alterations in mRNA level of key lipid metabolism enzymes in skeletal muscle of overweight and obese subjects following endurance exercise

    OpenAIRE

    Smith, Ira J.; Huffman, Kim M.; Durheim, Michael T.; Duscha, Brian D.; Kraus, William E.

    2008-01-01

    Endurance exercise (EE) leads to beneficial alterations in skeletal muscle lipid metabolism in overweight and obese individuals; however, the mechanisms of these improvements are poorly understood. The primary goal of the current investigation was to test the hypothesis that long-term EE training (6 mo) leads to alterations in the mRNA abundance of key lipid metabolism enzymes in skeletal muscle of overweight and obese middle-aged women and men. A secondary aim of this study was to investigat...

  14. β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes

    OpenAIRE

    Chang-Xiang Shi; Ming-Xia Zhao; Xiao-Dong Shu; Xiao-Qing Xiong; Jue-Jin Wang; Xing-Ya Gao; Qi Chen; Yue-Hua Li; Yu-Ming Kang; Guo-Qing Zhu

    2016-01-01

    β-aminoisobutyric acid (BAIBA) is a nature thymine catabolite, and contributes to exercise-induced protection from metabolic diseases. Here we show the therapeutical effects of BAIBA on hepatic endoplasmic reticulum (ER) stress and glucose/lipid metabolic disturbance in diabetes. Type 2 diabetes was induced by combined streptozotocin (STZ) and high-fat diet (HFD) in mice. Oral administration of BAIBA for 4 weeks reduced blood glucose and lipids levels, hepatic key enzymes of gluconeogenesis a...

  15. 6-Gingerol Protects against Nutritional Steatohepatitis by Regulating Key Genes Related to Inflammation and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2015-02-01

    Full Text Available Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH, appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl-3-decanone, a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 μmol/L treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day once daily for another four weeks. 6-Gingerol (100 mg/kg/day attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB, which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.

  16. Nicotinic acid supplementation in diet favored intramuscular fat deposition and lipid metabolism in finishing steers.

    Science.gov (United States)

    Yang, Zhu-Qing; Bao, Lin-Bin; Zhao, Xiang-Hui; Wang, Can-Yu; Zhou, Shan; Wen, Lu-Hua; Fu, Chuan-Bian; Gong, Jian-Ming; Qu, Ming-Ren

    2016-06-01

    Nicotinic acid (NA) acting as the precursor of NAD(+)/NADH and NADP(+)/NADPH, participates in many biochemical processes, e.g. lipid metabolism. The main purpose of this study was to investigate the effects of dietary NA on carcass traits, meat quality, blood metabolites, and fat deposition in Chinese crossbred finishing steers. Sixteen steers with the similar body weight and at the age of 24 months were randomly allocated into control group (feeding basal diet) and NA group (feeding basal diet + 1000 mg/kg NA). All experimental cattle were fed a 90% concentrate diet and 10% forage straw in a 120-day feeding experiment. The results showed that supplemental NA in diet increased longissimus area, intramuscular fat content (17.14% vs. 9.03%), marbling score (8.08 vs. 4.30), redness (a*), and chroma (C*) values of LD muscle, but reduced carcass fat content (not including imtramuscular fat), pH24 h and moisture content of LD muscle, along with no effect on backfat thickness. Besides, NA supplementation increased serum HDL-C concentration, but decreased the serum levels of LDL-C, triglyceride, non-esterified fatty acid, total cholesterol, and glycated serum protein. In addition, NA supplementation increased G6PDH and ICDH activities of LD muscle. These results suggested that NA supplementation in diet improves the carcass characteristics and beef quality, and regulates the compositions of serum metabolites. Based on the above results, NA should be used as the feed additive in cattle industry. PMID:27048556

  17. Camelina sativa: An ideal platform for the metabolic engineering and field production of industrial lipids.

    Science.gov (United States)

    Bansal, Sunil; Durrett, Timothy P

    2016-01-01

    Triacylglycerols (TAG) containing modified fatty acids with functionality beyond those found in commercially grown oil seed crops can be used as feedstocks for biofuels and bio-based materials. Over the years, advances have been made in transgenically engineering the production of various modified fatty acids in the model plant Arabidopsis thaliana. However, the inability to produce large quantities of transgenic seed has limited the functional testing of the modified oil. In contrast, the emerging oil seed crop Camelina sativa possesses important agronomic traits that recommend it as an ideal production platform for biofuels and industrial feedstocks. Camelina possesses low water and fertilizer requirements and is capable of yields comparable to other oil seed crops, particularly under stress conditions. Importantly, its relatively short growing season enables it to be grown as part of a double cropping system. In addition to these valuable agronomic features, Camelina is amenable to rapid metabolic engineering. The development of a simple and effective transformation method, combined with the availability of abundant transcriptomic and genomic data, has allowed the generation of transgenic Camelina lines capable of synthesizing high levels of unusual lipids. In some cases these levels have surpassed what was achieved in Arabidopsis. Further, the ability to use Camelina as a crop production system has allowed for the large scale growth of transgenic oil seed crops, enabling subsequent physical property testing. The application of new techniques such as genome editing will further increase the suitability of Camelina as an ideal platform for the production of biofuels and bio-materials. PMID:26107412

  18. 微藻脂肪合成与代谢调控%Lipid Biosynthesis and Metabolic Regulation in Microalgae

    Institute of Scientific and Technical Information of China (English)

    朱顺妮; 王忠铭; 尚常花; 周卫征; 杨康; 袁振宏

    2011-01-01

    With the increasingly severe energy and environmental problems,biodiesel from microalgae has become a hot topic.Compared with traditional oil crops,microalgae have advantages of rapid growth,high lipid content,non-occupation of arable land,etc.,which have been considered as a highly potential feedstock of biofuels.Although neutral lipids,especially triacylglycerols(TAG) which are the main feedstock of biodiesel production,can be accumulated in many algal cells under stress conditions,little is known about microalgal lipid synthesis and metabolic regulation so far.In order to better understand and manipulate microalgal lipid metabolism for improvement of lipid production,we present an overview of advances of lipid biosynthesis and metabolic regulation in microalgae,including TAG biosynthesis pathway,biochemical regulation and genetic engineering strategies.Effects of nutrition on lipid production are represented.Five genetic engineering strategies are summarized including enhancement of fatty acids synthesis pathway,enhancement of Kennedy pathway,regulation of alternative pathway of TAG,inhibition of competing pathway of lipid biosynthesis and lipid catabolism.The prospects of research on microalgal lipid metabolism are also discussed.%随着能源与环境问题的日益严峻,利用微藻生产生物柴油已经成为研究者们关注的焦点。与传统油料作物相比,微藻具有生长速度快、含油量高、不占用耕地等优势,是极具潜力的生物燃料生产原料。虽然许多微藻在压力条件下会在细胞内积累脂肪,特别是中性脂肪三酰甘油(TAG),它是生产生物柴油的主要原料,但目前对于微藻脂肪的合成和代谢调控还了解的很少。为了更好地理解和操纵微藻脂肪代谢以增强脂肪积累,本文综述了微藻脂肪合成与代谢调控的研究进展,包括TAG生物合成途径,提高脂肪积累的生化调控和基因工程策略,阐述了营养控制对脂肪

  19. Effects of in vitro Brevetoxin Exposure on Apoptosis and Cellular Metabolism in a Leukemic T Cell Line (Jurkat

    Directory of Open Access Journals (Sweden)

    John W. Sleasman

    2008-06-01

    Full Text Available Harmful algal blooms (HABs of the toxic dinoflagellate, Karenia brevis, produce red tide toxins, or brevetoxins. Significant health effects associated with red tide toxin exposure have been reported in sea life and in humans, with brevetoxins documented within immune cells from many species. The objective of this research was to investigate potential immunotoxic effects of brevetoxins using a leukemic T cell line (Jurkat as an in vitro model system. Viability, cell proliferation, and apoptosis assays were conducted using brevetoxin congeners PbTx-2, PbTx-3, and PbTx-6. The effects of in vitro brevetoxin exposure on cell viability and cellular metabolism or proliferation were determined using trypan blue and MTT (1-(4,5-dimethylthiazol-2-yl-3,5- diphenylformazan, respectively. Using MTT, cellular metabolic activity was decreased in Jurkat cells exposed to 5 - 10 μg/ml PbTx-2 or PbTx-6. After 3 h, no significant effects on cell viability were observed with any toxin congener in concentrations up to 10 μg/ml. Viability decreased dramatically after 24 h in cells treated with PbTx-2 or -6. Apoptosis, as measured by caspase-3 activity, was significantly increased in cells exposed to PbTx-2 or PbTx-6. In summary, brevetoxin congeners varied in effects on Jurkat cells, with PbTx-2 and PbTx-6 eliciting greater cellular effects compared to PbTx-3.

  20. Interactions between vertebrate hemoglobins and red cell proteins: Possible roles in regulating cellular metabolism and rheology

    DEFF Research Database (Denmark)

    Weber, Roy E.

    2007-01-01

    Red blood cells (RBCs) play a vital role in vertebrate metabolism. Tissue O2 delivery depends on their O2 transporting properties and rheology, an integral determinant of tissue perfusion. The mechanical characteristics and key metabolic characteristics of RBCs (such as glycolysis rate, pentose...

  1. Berberine Regulated Lipid Metabolism in the Presence of C75, Compound C, and TOFA in Breast Cancer Cell Line MCF-7

    Directory of Open Access Journals (Sweden)

    Wen Tan

    2015-01-01

    Full Text Available Berberine interfering with cancer reprogramming metabolism was confirmed in our previous study. Lipid metabolism and mitochondrial function were also the core parts in reprogramming metabolism. In the presence of some energy-related inhibitors, including C75, compound C, and TOFA, the discrete roles of berberine in lipid metabolism and mitochondrial function were elucidated. An altered lipid metabolism induced by berberine was observed under the inhibition of FASN, AMPK, and ACC in breast cancer cell MCF-7. And the reversion of berberine-induced lipid suppression indicated that ACC inhibition might be involved in that process instead of FASN inhibition. A robust apoptosis induced by berberine even under the inhibition of AMPK and lipid synthesis was also indicated. Finally, mitochondrial function regulation under the inhibition of AMPK and ACC might be in an ACL-independent manner. Undoubtedly, the detailed mechanisms of berberine interfering with lipid metabolism and mitochondrial function combined with energy-related inhibitors need further investigation, including the potential compensatory mechanisms for ATP production and the upregulation of ACL.

  2. Membrane texture induced by specific protein binding and receptor clustering: active roles for lipids in cellular function

    OpenAIRE

    Watkins, E. B.; Miller, C.E.; Majewski, J.; Kuhl, T L

    2011-01-01

    Biological membranes are complex, self-organized structures that define boundaries and compartmentalize space in living matter. Composed of a wide variety of lipid and protein molecules, these responsive surfaces mediate transmembrane signaling and material transport within the cell and with its environment. It is well known that lipid membrane properties change as a function of composition and phase state, and that protein-lipid interactions can induce changes in the membrane’s properties an...

  3. Effect and mechanism of waterborne prolonged Zn exposure influencing hepatic lipid metabolism in javelin goby Synechogobius hasta.

    Science.gov (United States)

    Huang, Chao; Luo, Zhi; Hogstrand, Christer; Chen, Feng; Shi, Xi; Chen, Qi-Liang; Song, Yu-Feng; Pan, Ya-Xiong

    2016-07-01

    The present study was conducted to determine the effect and mechanism of waterborne Zn exposure influencing hepatic lipid deposition and metabolism in javelin goby Synechogobius hasta. S. hasta were exposed to four waterborne Zn concentrations (Zn 0.005 [control], 0.18, 0.36 and 0.55 mg l(-1) , respectively) for 60 days. Sampling occurred at days 20, 40 and 60, respectively. Zn exposure increased Zn content, declined hepatic lipid content and reduced viscerosomatic and hepatosomatic indices and lipogenic enzyme activities, including 6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME) and fatty acid synthase (FAS). At days 20 and 60, Zn exposure decreased hepatic mRNA levels of 6PGD, G6PD, ME, FAS, acetyl-CoA carboxylase (ACC)α, ACCβ, hormone-sensitive lipase (HSL)a, HSLb, sterol-regulator element-binding protein (SREBP)-1, peroxisome proliferators-activated receptor (PPAR)α and PPARγ. However, the mRNA levels of CPT 1 and adipose triglyceride lipase increased following Zn exposure. On day 40, Zn exposure reduced hepatic mRNA expression of 6PGD, G6PD, ME, FAS, ACCα, ACCβ, HSLa, HSLb, SREBP-1 and PPARγ but increased mRNA expression of CPT 1, adipose triglyceride lipase and PPARα. General speaking, Zn exposure reduced hepatic lipid content by inhibiting lipogenesis and stimulating lipolysis. For the first time, the present study provided evidence that chronic Zn exposure differentially influenced mRNA expression and activities of genes and enzymes involved in lipogenic and lipolytic metabolism in a duration-dependent manner, and provided new insight into the relationship between metal elements and lipid metabolism. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26602879

  4. Function and regulation of lipid biology in Caenorhabditis elegans aging

    Directory of Open Access Journals (Sweden)

    Nicole Shangming Hou

    2012-05-01

    Full Text Available Rapidly expanding aging populations and a concomitant increase in the prevalence of age-related diseases are global health problems today. Over the past three decades, a large body of work has led to the identification of genes and regulatory networks that affect longevity and health span, often benefitting from the tremendous power of genetics in vertebrate and invertebrate model organisms. Interestingly, many of these factors appear linked to lipids, important molecules that participate in cellular signaling, energy metabolism, and structural compartmentalization. Despite the putative link between lipids and longevity, the role of lipids in aging remains poorly understood. Emerging data from the model organism Caenorhabditis elegans suggest that lipid composition may change during aging, as several pathways that influence aging also regulate lipid metabolism enzymes; moreover, some of these enzymes apparently play key roles in the pathways that affect the rate of aging. By understanding how lipid biology is regulated during C. elegans aging, and how it impacts molecular, cellular and organismal function, we may gain insight into novel ways to delay aging using genetic or pharmacological interventions. In the present review we discuss recent insights into the roles of lipids in C. elegans aging, including regulatory roles played by lipids themselves, the regulation of lipid metabolic enzymes, and the roles of lipid metabolism genes in the pathways that affect aging.

  5. Dynamics of human adipose lipid turnover in health and metabolic disease

    OpenAIRE

    Arner, Peter; Bernard, Samuel; Salehpour, Mehran; Possnert, Göran; Liebl, Jakob; Steier, Peter; Buchholz, Bruce A.; Eriksson, Mats; Arner, Erik; Hauner, Hans; Skurk, Thomas; Rydén, Mikael; Frayn, Keith N.; Spalding, Kirsty L.

    2011-01-01

    Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, lipid age was determined by measuring nuclear bomb test-derived 14C in adipocyte lipids. We report that during the average ten year life span of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult age...

  6. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

    Directory of Open Access Journals (Sweden)

    Maria Lankinen

    Full Text Available BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1 whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group, (2 Whole grain enriched diet (WGED group, which includes principally the same grain products as group (1, but with no change in fish or berry consumption, and (3 refined wheat breads (Control. Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3 long-chain PUFAs increased (False Discovery Rate p-values <0.05. Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3 PUFA. CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a

  7. Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice.

    Science.gov (United States)

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2016-01-01

    It is now broadly accepted that the nutritional environment in early life is a key factor in susceptibility to metabolic diseases. In this study, we evaluated the effects of maternal chromium restriction in vivo on the modulation of lipid metabolism and the mechanisms involved in this process. Sixteen pregnant C57BL mice were randomly divided into two dietary treatments: a control (C) diet group and a low chromium (L) diet group. The diet treatment was maintained through gestation and lactation period. After weaning, some of the pups continued with either the control diet or low chromium diet (CC or LL), whereas other pups switched to another diet (CL or LC). At 32 weeks of age, serum lipid metabolism, proinflammatory indexes, oxidative stress and anti-oxidant markers, and DNA methylation status in adipose tissue were measured. The results indicated that the maternal low chromium diet increased body weight, fat pad weight, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and oxidized glutathione (GSSG). There was a decrease in serum reduced/oxidized glutathione (GSH/GSSG) ratio at 32 weeks of age in female offspring. From adipose tissue, we identified 1214 individual hypomethylated CpG sites and 411 individual hypermethylated CpG sites in the LC group when compared to the CC group. Pathway analysis of the differential methylation genes revealed a significant increase in hypomethylated genes in the mitogen-activated protein kinase (MAPK) signaling pathway in the LC group. Our study highlights the importance of the MAPK signaling pathway in epigenetic changes involved in the lipid metabolism of the offspring from chromium-restricted dams. PMID:27517955

  8. Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice

    Science.gov (United States)

    Zhang, Qian; Sun, Xiaofang; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2016-01-01

    It is now broadly accepted that the nutritional environment in early life is a key factor in susceptibility to metabolic diseases. In this study, we evaluated the effects of maternal chromium restriction in vivo on the modulation of lipid metabolism and the mechanisms involved in this process. Sixteen pregnant C57BL mice were randomly divided into two dietary treatments: a control (C) diet group and a low chromium (L) diet group. The diet treatment was maintained through gestation and lactation period. After weaning, some of the pups continued with either the control diet or low chromium diet (CC or LL), whereas other pups switched to another diet (CL or LC). At 32 weeks of age, serum lipid metabolism, proinflammatory indexes, oxidative stress and anti-oxidant markers, and DNA methylation status in adipose tissue were measured. The results indicated that the maternal low chromium diet increased body weight, fat pad weight, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and oxidized glutathione (GSSG). There was a decrease in serum reduced/oxidized glutathione (GSH/GSSG) ratio at 32 weeks of age in female offspring. From adipose tissue, we identified 1214 individual hypomethylated CpG sites and 411 individual hypermethylated CpG sites in the LC group when compared to the CC group. Pathway analysis of the differential methylation genes revealed a significant increase in hypomethylated genes in the mitogen-activated protein kinase (MAPK) signaling pathway in the LC group. Our study highlights the importance of the MAPK signaling pathway in epigenetic changes involved in the lipid metabolism of the offspring from chromium-restricted dams. PMID:27517955

  9. Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome: baseline and post intervention effects

    Directory of Open Access Journals (Sweden)

    Betts Nancy M

    2009-09-01

    Full Text Available Abstract Background Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols. Methods Females (n = 16 with 3 features of metabolic syndrome (waist circumference >35 inches, triglycerides > 150 mg/dL, fasting glucose > 100 mg/dL and 130/85 mm Hg were enrolled in the study. Subjects consumed two cups of the strawberry drink daily for four weeks. Each cup had 25 g FSP blended in water. Fasting blood draws, anthropometrics, dietary analyses, and blood pressure measurements were done at baseline and 4 weeks. Biomarkers of oxidative stress and inflammation were measured using ELISA techniques. Plasma ellagic acid was measured using HPLC-UV techniques. Results Total cholesterol and LDL-cholesterol levels were significantly lower at 4 weeks versus baseline (-5% and -6%, respectively, p

  10. Comparative effect of olmesartan and candesartan on lipid metabolism and renal function in patients with hypertension: a retrospective observational study

    Directory of Open Access Journals (Sweden)

    Nakayama Tomohiro

    2011-08-01

    Full Text Available Abstract Background Angiotensin II receptor blockers (ARBs, including olmesartan and candesartan, are widely used antihypertensive agents. Many clinical studies have demonstrated that ARBs have organ-protecting effects, e.g., cardioprotection, vasculoprotection and renoprotection. However, the effect of prolonged olmesartan monotherapy on lipid metabolism in patients with hypertension is less well studied. We performed a retrospective observational study to compare the effects of olmesartan with those of candesartan, focusing on lipid metabolism and renal function. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and Feb 28, 2011, to identify cohorts of new olmesartan users (n = 168 and candesartan users (n = 266. We used propensity-score weighting to adjust for differences in all covariates (age, sex, comorbid diseases, previous drugs between olmesartan and candesartan users, and compared serum chemical data including serum triglyceride (TG, LDL-cholesterol (LDL-C, total cholesterol (TC, potassium, creatinine and urea nitrogen. The mean exposure of olmesartan and candesartan users was 126.1 and 122.8 days, respectively. Results After adjustment, there were no statistically significant differences in all covariates between olmesartan and candesartan users. The mean age was 60.7 and 61.0 years, and 33.4% and 33.7% of olmesartan and candesartan users were women, respectively. There were no statistically significant differences in mean values for all laboratory tests between baseline and during the exposure period in both olmesartan and candesartan users. In olmesartan users, the reduction of serum TG level was significant in comparison with that in candesartan users. Other parameters of lipid profile and renal function showed no statistically significant difference in the change from baseline to during the exposure period between olmesartan and candesartan users. Conclusions

  11. Potential of IL-33 for Preventing the Kidney Injury via Regulating the Lipid Metabolism in Gout Patients.

    Science.gov (United States)

    Duan, Lihua; Huang, Yan; Su, Qun; Lin, Qingyan; Liu, Wen; Luo, Jiao; Yu, Bing; He, Yan; Qian, Hongyan; Liu, Yuan; Chen, Jie; Shi, Guixiu

    2016-01-01

    Interleukin-33 (IL-33), the most recently discovered member of the IL-1 superfamily, has been linked to several human pathologies including autoimmune diseases, sepsis, and allergy through its specific IL-1 receptor ST2. However, there is little information regarding the role of IL-33 in gout. In this study, we investigated the potential role of IL-33 in gout patients. The serum level of IL-33 was measured by ELISA, and the clinical and laboratory parameters, serum creatinine, urea, and lipid, were extracted from medical record system. The serum IL-33 expression was predominantly increased in gout patients compared to healthy controls, and the IL-33 levels were higher in patients without kidney injury. Furthermore, IL-33 showed a negative correlation with biomarkers of kidney injury, such as CRE and urea. The lipid metabolism dysfunction, tophi, and hypertension are the common reasons for kidney injury in gout. Interestingly, inverse and positive correlation of IL-33 expression was observed in LDL and HDL, respectively. However, there was no significant alteration in the gout patients with hypertension and tophi. These data suggested that IL-33 might act as a protective role in kidney injury through regulating the lipid metabolism in gout. PMID:27579324

  12. Tissue- and paralogue-specific functions of acyl-CoA-binding proteins in lipid metabolism in C. elegans

    DEFF Research Database (Denmark)

    Elle, Ida Coordt; Simonsen, Karina Trankjær; Olsen, Louise Cathrine Braun; Birck, Pernille Kirstine; Ehmsen, Sidse; Tuck, Simon; Le, Thuc Timothy; Færgeman, Nils J.

    2011-01-01

    Acyl-CoA binding protein (ACBP) is a small, primarily cytosolic protein that binds acyl-CoA esters with high specificity and affinity. ACBP has been identified in all eukaryotic species, indicating that it performs a basal cellular function. However, differential tissue expression and the existence...... of several ACBP paralogues in many eukaryotic species indicate that these proteins serve distinct functions. The nematode Caenorhabditis elegans expresses seven ACBPs; four basal forms and three ACBP-domain proteins. We find that each of these paralogues is capable of complementing growth of ACBP...... levels and aberrant lipid droplet morphology and number in the intestine. We also show that worms lacking ACBP-2 show a severe decrease in the β-oxidation of unsaturated fatty acids. A quadruple mutant, lacking all basal ACBPs, is slightly developmentally delayed, displays abnormal intestinal lipid...

  13. The multifaceted role of mTORC1 in the control of lipid metabolism

    OpenAIRE

    Ricoult, Stéphane J H; Manning, Brendan D.

    2012-01-01

    mTORC1 is emerging as a central regulator of lipid homeostasis. This review discusses the growing evidence for the functional importance of mTORC1 signalling in controlling mammalian lipid synthesis, oxidation, transport, storage and lipolysis, as well as adipocyte differentiation and function.

  14. Post-exercise adipose tissue and skeletal muscle lipid metabolism in humans

    DEFF Research Database (Denmark)

    Mulla, N A; Simonsen, L; Bülow, J

    2000-01-01

    One purpose of the present experiments was to examine whether the relative workload or the absolute work performed is the major determinant of the lipid mobilization from adipose tissue during exercise. A second purpose was to determine the co-ordination of skeletal muscle and adipose tissue lipid...

  15. The effects of chemotherapeutics on cellular metabolism and consequent immune recognition

    OpenAIRE

    Newell, M Karen; Melamede, Robert; Villalobos-Menuey, Elizabeth; Swartzendruber, Douglas; Trauger, Richard; Camley, Robert E; Crisp, William

    2004-01-01

    A widely held view is that oncolytic agents induce death of tumor cells directly. In this report we review and discuss the apoptosis-inducing effects of chemotherapeutics, the effects of chemotherapeutics on metabolic function, and the consequent effects of metabolic function on immune recognition. Finally, we propose that effective chemotherapeutic and/or apoptosis-inducing agents, at concentrations that can be achieved physiologically, do not kill tumor cells directly. Rather, we suggest th...

  16. SIRT1 and energy metabolism

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Li

    2013-01-01

    Sirtuin 1 (SIRT1) is the most conserved mammalian NAD+-dependent protein deacetylase that has emerged as a key metabolic sensor in various metabolic tissues.In response to different environmental stimuli,SIRT1 directly links the cellular metabolic status to the chromatin structure and the regulation of gene expression,thereby modulating a variety of cellular processes such as energy metabolism and stress response.Recent studies have shown that SIRT1 controls both glucose and lipid metabolism in the liver,promotes fat mobilization and stimulates brown remodeling of the white fat in white adipose tissue,controls insulin secretion in the pancreas,senses nutrient availability in the hypothalamus,influences obesityinduced inflammation in macrophages,and modulates the activity of circadian clock in metabolic tissues.This review focuses on the role of SIRT1 in regulating energy metabolism at different metabolic tissues.

  17. MALDI Mass Spectrometry Imaging of Lipids and Gene Expression Reveals Differences in Fatty Acid Metabolism between Follicular Compartments in Porcine Ovaries

    Directory of Open Access Journals (Sweden)

    Svetlana Uzbekova

    2015-03-01

    Full Text Available In mammals, oocytes develop inside the ovarian follicles; this process is strongly supported by the surrounding follicular environment consisting of cumulus, granulosa and theca cells, and follicular fluid. In the antral follicle, the final stages of oogenesis require large amounts of energy that is produced by follicular cells from substrates including glucose, amino acids and fatty acids (FAs. Since lipid metabolism plays an important role in acquiring oocyte developmental competence, the aim of this study was to investigate site-specificity of lipid metabolism in ovaries by comparing lipid profiles and expression of FA metabolism-related genes in different ovarian compartments. Using MALDI Mass Spectrometry Imaging, images of porcine ovary sections were reconstructed from lipid ion signals for the first time. Cluster analysis of ion spectra revealed differences in spatial distribution of lipid species among ovarian compartments, notably between the follicles and interstitial tissue. Inside the follicles analysis differentiated follicular fluid, granulosa, theca and the oocyte-cumulus complex. Moreover, by transcript quantification using real time PCR, we showed that expression of five key genes in FA metabolism significantly varied between somatic follicular cells (theca, granulosa and cumulus and the oocyte. In conclusion, lipid metabolism differs between ovarian and follicular compartments.

  18. Diets enriched in trans-11 vaccenic acid alleviate ectopic lipid accumulation in a rat model of NAFLD and metabolic syndrome.

    Science.gov (United States)

    Jacome-Sosa, M Miriam; Borthwick, Faye; Mangat, Rabban; Uwiera, Richard; Reaney, Martin J; Shen, Jianheng; Quiroga, Ariel D; Jacobs, René L; Lehner, Richard; Proctor, Spencer D; Nelson, Randal C

    2014-07-01

    Trans11-18:1 (vaccenic acid, VA) is one of the most predominant naturally occurring trans fats in our food chain and has recently been shown to exert hypolipidemic effects in animal models. In this study, we reveal new mechanism(s) by which VA can alter body fat distribution, energy utilization and dysfunctional lipid metabolism in an animal model of obesity displaying features of the metabolic syndrome (MetS). Obese JCR:LA-cp rats were assigned to a control diet that included dairy-derived fat or the control diet supplemented with 1% VA. VA reduced total body fat (-6%), stimulated adipose tissue redistribution [reduced mesenteric fat (-17%) while increasing inguinal fat mass (29%)] and decreased adipocyte size (-44%) versus control rats. VA supplementation also increased metabolic rate (7%) concomitantly with an increased preference for whole-body glucose utilization for oxidation and increased insulin sensitivity [lower HOMA-IR (-59%)]. Further, VA decreased nonalcoholic fatty liver disease activity scores (-34%) and reduced hepatic (-27%) and intestinal (-39%) triglyceride secretion relative to control diet, while exerting differential transcriptional regulation of SREBP1 and FAS amongst other key genes in the liver and the intestine. Adding VA to dairy fat alleviates features of MetS potentially by remodeling adipose tissue and attenuating ectopic lipid accumulation in a rat model of obesity and MetS. Increasing VA content in the diet (naturally or by fortification) may be a useful approach to maximize the health value of dairy-derived fats. PMID:24775093

  19. Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics

    OpenAIRE

    Mudrich Epouse Dorosz, Susann Antonia; Pietzke, Matthias; Zasada, Christin

    2014-01-01

    Background Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. Results Here, we descri...

  20. Decoding the dynamics of cellular metabolism and the action of 3-bromopyruvate and 2-deoxyglucose using pulsed stable isotope-resolved metabolomics

    OpenAIRE

    Pietzke, M.; Zasada, C.; Mudrich, S.; Kempa, S.

    2014-01-01

    BACKGROUND: Cellular metabolism is highly dynamic and continuously adjusts to the physiological program of the cell. The regulation of metabolism appears at all biological levels: (post-) transcriptional, (post-) translational, and allosteric. This regulatory information is expressed in the metabolome, but in a complex manner. To decode such complex information, new methods are needed in order to facilitate dynamic metabolic characterization at high resolution. RESULTS: Here, we describe pul...