Positive Regulatory Control Loop between Gut Leptin and Intestinal GLUT2/GLUT5 Transporters Links to Hepatic Metabolic Functions in Rodents

International audienceBACKGROUND AND AIMS: The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. METHODOLOGY: Wistar rats, wild type and AMPKalpha(2) (-/-) mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. PRINCIPAL FINDINGS: First, in vitro luminal leptin activating its receptors coupled to PKCbetaII and AMPKalpha, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. CONCLUSION/SIGNIFICANCE: These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious

Punicic Acid a Conjugated Linolenic Acid Inhibits TNFα-Induced Neutrophil Hyperactivation and Protects from Experimental Colon Inflammation in Rats

BACKGROUND:Neutrophils play a major role in inflammation by releasing large amounts of ROS produced by NADPH-oxidase and myeloperoxidase (MPO). The proinflammatory cytokine TNFalpha primes ROS production through phosphorylation of the NADPH-oxidase subunit p47phox on Ser345. Conventional anti-inflammatory therapies remain partially successful and may have side effects. Therefore, regulation of neutrophil activation by natural dietary components represents an alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases. The aim of this study was to assess the effect of punicic acid, a conjugated linolenic fatty acid from pomegranate seed oil on TNFalpha-induced neutrophil hyperactivation in vitro and on colon inflammation in vivo. METHODOLOGY AND PRINCIPAL FINDINGS:We analyzed the effect of punicic acid on TNFalpha-induced neutrophil upregulation of ROS production in vitro and on TNBS-induced rat colon inflammation. Results show that punicic acid inhibited TNFalpha-induced priming of ROS production in vitro while preserving formyl-methionyl-leucyl-phenylalanine (fMLP)-induced response. This effect was mediated by the inhibition of Ser345-p47phox phosphorylation and upstream kinase p38MAPK. Punicic acid also inhibited fMLP- and TNFalpha+fMLP-induced MPO extracellular release from neutrophils. In vivo experiments showed that punicic acid and pomegranate seed oil intake decreased neutrophil-activation and ROS/MPO-mediated tissue damage as measured by F2-isoprostane release and protected rats from TNBS-induced colon inflammation. CONCLUSIONS/SIGNIFICANCE:These data show that punicic acid exerts a potent anti-inflammatory effect through inhibition of TNFalpha-induced priming of NADPH oxidase by targeting the p38MAPKinase/Ser345-p47phox-axis and MPO release. This natural dietary compound may provide a novel alternative therapeutic strategy in inflammatory diseases such as inflammatory bowel diseases

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry

Luc-Francis Genicot, Patricia Butil, Sabine De Jonghe, Bernadette Lozet, et Philippe WEBER, Le patrimoine rural de Wallonie. La maison paysanne. T. I : Des modèles aux réalités. Bruxelles, Crédit Communal, 1996

Lettéron Isabelle. Luc-Francis Genicot, Patricia Butil, Sabine De Jonghe, Bernadette Lozet, et Philippe WEBER, Le patrimoine rural de Wallonie. La maison paysanne. T. I : Des modèles aux réalités. Bruxelles, Crédit Communal, 1996. In: Histoire & Sociétés Rurales, n°7, 1er semestre 1997. pp. 213-215

Reconstruction of a saline, lacustrine carbonate system (Priabonian, St-Chaptes Basin, SE France): depositional models, paleogeographic and paleoclimatic implications.

28 pagesInternational audienceA 220-m thick carbonate-dominated succession has been deposited in shallow-water, saline lake environments during the early to middle Priabonian (MP17A-MP18 mammal zones) in the Saint-Chaptes Basin (south–east France). The palaeoenvironmental, paleoclimatic and palaeogeographic significance of such saline lake carbonates has been deciphered on the basis of a multi-proxy analyses including: 1) depositional and diagenetic features; 2) biological components (molluscs, benthic foraminifera, characean gyrogonites, spores and pollens); 3) carbon and oxygen stable isotopes; 4) trace elements; and 5) clay mineralogy. Five stages of lacustrine system evolution have been identified: 1) fresh-water closed lake under dry climate (unit U1); 2) fresh to brackish water lacustrine deltaic system with a mixed carbonate-siliciclastic sedimentation under relatively wet climatic conditions (unit U2); 3) salt-water lacustrine carbonate system under humid climatic setting (unit U3); 4) evaporitic lake (unit U4); and 5) closed lake with shallow-water carbonate sedimentation under subtropical to Mediterranean climate with dry seasons (unit U5). Upper Eocene aridification is evidenced to have started as early as the earliest Priabonian (unit U1: MP17A mammal zone). A change from humid to dryer climatic conditions is recorded between units U3 and U4. The early to middle Priabonian saline lake is interpreted as an athalassic (inland) lake that have been transiently connected with neighboring salt lakes influenced by seawater and/or fed with sulfates deriving from recycling of evaporites. Maximum of connection with neighboring saline lakes (Mormoiron Basin, Camargue and Central grabens, Hérault Basin) likely occurred during unit U3 and at the base of unit U5. The most likely sources of salts of these adjacent basins are: 1) Triassic evaporites derived from salt-diapirs (Rhône valley) or from paleo-outcrops located east of the Durance fault or offshore in the Gulf of Lion; or 2) marine incursions from the south, through Paleogene grabens in the Gulf of Lion

Central role of mitochondria in drug-induced liver injury.

International audienceA frequent mechanism for drug-induced liver injury (DILI) is the formation of reactive metabolites that trigger hepatitis through direct toxicity or immune reactions. Both events cause mitochondrial membrane disruption. Genetic or acquired factors predispose to metabolite-mediated hepatitis by increasing the formation of the reactive metabolite, decreasing its detoxification, or by the presence of critical human leukocyte antigen molecule(s). In other instances, the parent drug itself triggers mitochondrial membrane disruption or inhibits mitochondrial function through different mechanisms. Drugs can sequester coenzyme A or can inhibit mitochondrial β-oxidation enzymes, the transfer of electrons along the respiratory chain, or adenosine triphosphate (ATP) synthase. Drugs can also destroy mitochondrial DNA, inhibit its replication, decrease mitochondrial transcripts, or hamper mitochondrial protein synthesis. Quite often, a single drug has many different effects on mitochondrial function. A severe impairment of oxidative phosphorylation decreases hepatic ATP, leading to cell dysfunction or necrosis; it can also secondarily inhibit ß-oxidation, thus causing steatosis, and can also inhibit pyruvate catabolism, leading to lactic acidosis. A severe impairment of β-oxidation can cause a fatty liver; further, decreased gluconeogenesis and increased utilization of glucose to compensate for the inability to oxidize fatty acids, together with the mitochondrial toxicity of accumulated free fatty acids and lipid peroxidation products, may impair energy production, possibly leading to coma and death. Susceptibility to parent drug-mediated mitochondrial dysfunction can be increased by factors impairing the removal of the toxic parent compound or by the presence of other medical condition(s) impairing mitochondrial function. New drug molecules should be screened for possible mitochondrial effects