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  1. Article ; Online: Saline-induced coronary hyperemia with continuous intracoronary thermodilution is mediated by intravascular hemolysis.

    Gallinoro, Emanuele / Candreva, Alessandro / Fernandez-Peregrina, Estefania / Bailleul, Els / Meeus, Peter / Sonck, Jeroen / Bermpeis, Konstantinos / Bertolone, Dario Tino / Esposito, Giuseppe / Paolisso, Pasquale / Heggermont, Ward / Adjedj, Julien / Barbato, Emanuele / Collet, Carlos / De Bruyne, Bernard

    Atherosclerosis

    2022  Volume 352, Page(s) 46–52

    Abstract: Background and aims: Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through a dedicated infusion catheter (RayFlow®). A saline infusion rate at 15-20 mL/min induces an immediate, steady-state, maximal ... ...

    Abstract Background and aims: Absolute coronary flow can be measured by intracoronary continuous thermodilution of saline through a dedicated infusion catheter (RayFlow®). A saline infusion rate at 15-20 mL/min induces an immediate, steady-state, maximal microvascular vasodilation. The mechanism of this hyperemic response remains unclear. We aimed to test whether local hemolysis is a potential mechanism of saline-induced coronary hyperemia.
    Methods: Twelve patients undergoing left and right catheterization were included. The left coronary artery and the coronary sinus were selectively cannulated. Absolute resting and hyperemic coronary flow were measured by continuous intracoronary thermodilution. Arterial and venous samples were collected from the coronary artery and the coronary sinus in five phases: baseline (BL); resting flow measurement (Rest, saline infusion at 10 mL/min); hyperemia (Hyperemia, saline infusion at 20 mL/min); post-hyperemia (Post-Hyperemia, 2 min after the cessation of saline infusion); and control phase (Control, during infusion of saline through the guide catheter at 30 mL/min).
    Results: Hemolysis was visually detected only in the centrifugated venous blood samples collected during the Hyperemia phase. As compared to Rest, during Hyperemia both LDH (131.50 ± 21.89 U/dL [Rest] and 258.33 ± 57.40 U/dL [Hyperemia], p < 0.001) and plasma free hemoglobin (PFHb, 4.92 ± 3.82 mg/dL [Rest] and 108.42 ± 46.58 mg/dL [Hyperemia], p < 0.001) significantly increased in the coronary sinus. The percentage of hemolysis was significantly higher during the Hyperemia phase (0.04 ± 0.02% [Rest] vs 0.89 ± 0.34% [Hyperemia], p < 0.001).
    Conclusions: Saline-induced hyperemia through a dedicated intracoronary infusion catheter is associated with hemolysis. Vasodilatory compounds released locally, like ATP, are likely ultimately responsible for localized microvascular vasodilation.
    MeSH term(s) Coronary Circulation/physiology ; Coronary Vessels ; Hemolysis ; Humans ; Hyperemia ; Thermodilution
    Language English
    Publishing date 2022-05-17
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2022.05.011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Weaning from veno-arterial extra-corporeal membrane oxygenation: which strategy to use?

    Ortuno, Sofia / Delmas, Clément / Diehl, Jean-Luc / Bailleul, Clotilde / Lancelot, Aymeric / Naili, Mahassen / Cholley, Bernard / Pirracchio, Romain / Aissaoui, Nadia

    Annals of cardiothoracic surgery

    2018  Volume 8, Issue 1, Page(s) E1–E8

    Abstract: Refractory cardiogenic shock patients may be rescued by veno-arterial extracorporeal membrane oxygenation (VA ECMO). After a few days of mechanical assistance, the device can sometimes be successfully removed if the patient has partially or fully ... ...

    Abstract Refractory cardiogenic shock patients may be rescued by veno-arterial extracorporeal membrane oxygenation (VA ECMO). After a few days of mechanical assistance, the device can sometimes be successfully removed if the patient has partially or fully recovered from the condition that required the use of ECMO. The percentage of patients with refractory cardiogenic shock who are successfully weaned from ECMO varies from 31% to 76%. Weaning does not mean survival, because 20% to 65% of patients weaned from VA ECMO support do not survive to hospital discharge. The high death rate after successful weaning shows that many questions remain unresolved in this field. In this review, we will discuss the various factors influencing survival and a successful weaning from VA ECMO, in addition to weaning approaches proposed in the literature. Based on this information, we will propose a strategy to optimize the weaning process.
    Language English
    Publishing date 2018-10-22
    Publishing country China
    Document type Editorial
    ZDB-ID 2713627-9
    ISSN 2304-1021 ; 2225-319X
    ISSN (online) 2304-1021
    ISSN 2225-319X
    DOI 10.21037/acs.2018.08.05
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Multifaceted Inhibitory Effects of an Alkylquinolone on the Diatom Phaeodactylum tricornutum.

    Dow, Lachlan / Stock, Frederike / Peltekis, Alexandra / Szamosvári, Dávid / Prothiwa, Michaela / Lapointe, Adrien / Böttcher, Thomas / Bailleul, Benjamin / Vyverman, Wim / Kroth, Peter G / Lepetit, Bernard

    Chembiochem : a European journal of chemical biology

    2020  Volume 21, Issue 8, Page(s) 1206–1216

    Abstract: The mechanisms underlying interactions between diatoms and bacteria are crucial to understand diatom behaviour and proliferation, and can result in far-reaching ecological consequences. Recently, 2-alkyl-4-quinolones have been isolated from marine ... ...

    Abstract The mechanisms underlying interactions between diatoms and bacteria are crucial to understand diatom behaviour and proliferation, and can result in far-reaching ecological consequences. Recently, 2-alkyl-4-quinolones have been isolated from marine bacteria, both of which (the bacterium and isolated chemical) inhibited growth of microalgae, suggesting these compounds could mediate diatom-bacteria interactions. The effects of several quinolones on three diatom species have been investigated. The growth of all three was inhibited, with half-maximal inhibitory concentrations reaching the sub-micromolar range. By using multiple techniques, dual inhibition mechanisms were uncovered for 2-heptyl-4-quinolone (HHQ) in Phaeodactylum tricornutum. Firstly, photosynthetic electron transport was obstructed, primarily through inhibition of the cytochrome b
    MeSH term(s) 4-Quinolones/pharmacology ; Adenosine Triphosphate/metabolism ; Chloroplasts/drug effects ; Cytochrome b6f Complex/antagonists & inhibitors ; Diatoms/drug effects ; Diatoms/growth & development ; Mitochondria/drug effects ; Mitochondria/physiology ; Photosynthesis ; Plastids/drug effects ; Thylakoids/metabolism
    Chemical Substances 2-heptyl-4-quinolone ; 4-Quinolones ; Adenosine Triphosphate (8L70Q75FXE) ; Cytochrome b6f Complex (9035-40-9)
    Language English
    Publishing date 2020-01-28
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.201900612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Pelvic exam in Gynecology and Obstetrics: French Guidelines for Clinical Practice.

    Deffieux, Xavier / Pizzoferrato, Anne-Cécile / Gaucher, Laurent / Rousset-Jablonski, Christine / Le Ray, Camille / Brillac, Thierry / Maruani, Julia / Maitrot-Mantelet, Lorraine / Mignot, Stéphanie / Athiel, Yoann / Baffet, Hortense / Bailleul, Alexandre / Bernard, Valérie / Bourdon, Mathilde / Cardaillac, Claire / Carneiro, Yaritza / Chariot, Patrick / Corroenne, Romain / Dabi, Yohann /
    Dahlem, Laurence / Frank, Sophie / Freyens, Anne / Grouthier, Virginie / Hernandez, Isabelle / Iraola, Elisabeth / Lambert, Marie / Lauchet, Nadege / Legendre, Guillaume / Le Lous, Maela / Louis-Vahdat, Christine / Martinat Sainte-Beuve, Anne / Masson, Marine / Matteo, Caroline / Pinton, Anne / Sabbagh, Emmanuelle / Sallee, Camille / Thubert, Thibault / Heron, Isabelle / Artzner, France / Tavenet, Arounie / Gantois, Adrien / Fauconnier, Arnaud

    European journal of obstetrics, gynecology, and reproductive biology

    2023  Volume 291, Page(s) 131–140

    MeSH term(s) Female ; Pregnancy ; Humans ; Gynecology/education ; Gynecological Examination ; Obstetrics/education ; Internship and Residency
    Language English
    Publishing date 2023-10-10
    Publishing country Ireland
    Document type Journal Article
    ZDB-ID 190605-7
    ISSN 1872-7654 ; 0301-2115 ; 0028-2243
    ISSN (online) 1872-7654
    ISSN 0301-2115 ; 0028-2243
    DOI 10.1016/j.ejogrb.2023.10.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Wind storm risk management: sensitivity of return period calculations and spread on the territory

    Mornet, Alexandre / Thomas Opitz / Michel Luzi / Stéphane Loisel / Bernard Bailleul

    Stochastic environmental research and risk assessment. 2017 Oct., v. 31, no. 8

    2017  

    Abstract: Modeling and forecasting damage from wind storms is a major issue for insurance companies. In this article, we focus on the sensitivity of estimations of return periods for extreme events with respect to modeling assumptions and the type of input data. ... ...

    Abstract Modeling and forecasting damage from wind storms is a major issue for insurance companies. In this article, we focus on the sensitivity of estimations of return periods for extreme events with respect to modeling assumptions and the type of input data. Numerous variables play a role: the quality of data concerning the location of insured buildings and weather report homogeneity, missing updates for correcting non-stationarities concerning the insurance portfolio history, ground roughness or climate change, the evolution of the model after an unprecedented event such as the Lothar storm observed in 1999 in Europe, temporal aggregation of daily events over several days, where events could span over several days up to one week, and storm trajectories, which could change due to global warming or sweep larger areas. Our work explores three important aspects. First, we highlight the geographic heterogeneity of the spatial distribution of wind speeds and the resulting damages. Therefore, we propose to partition the French territory into 6 relatively homogeneous storm zones, based on the dependence among observed wind speeds and geographic distance. Second, we extend a storm index—defined in Mornet et al. (Risk Anal 35:2029–2056, 2015)—to take into account geographic heterogeneity, and we analyze its tail behavior to show the difficulties met to obtain reliable results on extreme events. Third, we explore the calculation of Solvency Capital Requirements based on a model that we propose for the annual claim amount distribution. The purpose of our analysis is to quantify and to point out the high level of uncertainty in the computation of return periods and of other quantities strongly influenced by extreme events.
    Keywords buildings ; business enterprises ; capital ; global warming ; insurance ; models ; risk ; risk management ; roughness ; storms ; uncertainty ; wind speed ; Europe
    Language English
    Dates of publication 2017-10
    Size p. 1977-1995.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    ZDB-ID 1481263-0
    ISSN 1436-3259 ; 1436-3240 ; 0931-1955
    ISSN (online) 1436-3259
    ISSN 1436-3240 ; 0931-1955
    DOI 10.1007/s00477-016-1367-7
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Examen pelvien en gynécologie et obstétrique : recommandations pour la pratique clinique.

    Deffieux, Xavier / Rousset-Jablonski, Christine / Gantois, Adrien / Brillac, Thierry / Maruani, Julia / Maitrot-Mantelet, Lorraine / Mignot, Stéphanie / Gaucher, Laurent / Athiel, Yoann / Baffet, Hortense / Bailleul, Alexandre / Bernard, Valérie / Bourdon, Mathilde / Cardaillac, Claire / Carneiro, Yaritza / Chariot, Patrick / Corroenne, Romain / Dabi, Yohann / Dahlem, Laurence /
    Frank, Sophie / Freyens, Anne / Grouthier, Virginie / Hernandez, Isabelle / Iraola, Elisabeth / Lambert, Marie / Lauchet, Nadege / Legendre, Guillaume / Le Lous, Maela / Louis-Vahdat, Christine / Martinat Sainte-Beuve, Anne / Masson, Marine / Matteo, Caroline / Pinton, Anne / Sabbagh, Emmanuelle / Sallee, Camille / Thubert, Thibault / Heron, Isabelle / Pizzoferrato, Anne-Cécile / Artzner, France / Tavenet, Arounie / Le Ray, Camille / Fauconnier, Arnaud

    Gynecologie, obstetrique, fertilite & senologie

    2023  Volume 51, Issue 6, Page(s) 297–330

    Abstract: Objective: To provide guidelines for the pelvic clinical exam in gynecology and obstetrics.: Material and methods: A multidisciplinary experts consensus committee of 45 experts was formed, including representatives of patients' associations and users ...

    Title translation Pelvic exam in gynecology and obstetrics: Guidelines for clinical practice.
    Abstract Objective: To provide guidelines for the pelvic clinical exam in gynecology and obstetrics.
    Material and methods: A multidisciplinary experts consensus committee of 45 experts was formed, including representatives of patients' associations and users of the health system. The entire guidelines process was conducted independently of any funding. The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized.
    Methods: The committee studied 40 questions within 4 fields for symptomatic or asymptomatic women (emergency conditions, gynecological consultation, gynecological diseases, obstetrics, and pregnancy). Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® methodology.
    Results: The experts' synthesis work and the application of the GRADE method resulted in 27 recommendations. Among the formalized recommendations, 17 present a strong agreement, 7 a weak agreement and 3 an expert consensus agreement. Thirteen questions resulted in an absence of recommendation due to lack of evidence in the literature.
    Conclusions: The need to perform clinical examination in gynecological and obstetrics patients was specified in 27 pre-defined situations based on scientific evidence. More research is required to investigate the benefit in other cases.
    MeSH term(s) Female ; Humans ; Pregnancy ; Consensus ; Genital Diseases, Female/diagnosis ; Genital Diseases, Female/therapy ; Gynecological Examination ; Gynecology ; Obstetrics
    Language French
    Publishing date 2023-05-22
    Publishing country France
    Document type English Abstract ; Practice Guideline ; Review ; Journal Article
    ZDB-ID 2887456-0
    ISSN 2468-7189
    ISSN (online) 2468-7189
    DOI 10.1016/j.gofs.2023.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: N-Acyl Homoserine Lactone Derived Tetramic Acids Impair Photosynthesis in Phaeodactylum tricornutum.

    Stock, Frederike / Syrpas, Michail / Graff van Creveld, Shiri / Backx, Simon / Blommaert, Lander / Dow, Lachlan / Stock, Willem / Ruysbergh, Ewout / Lepetit, Bernard / Bailleul, Benjamin / Sabbe, Koen / De Kimpe, Norbert / Willems, Anne / Kroth, Peter G / Vardi, Assaf / Vyverman, Wim / Mangelinckx, Sven

    ACS chemical biology

    2019  Volume 14, Issue 2, Page(s) 198–203

    Abstract: Marine bacteria contribute substantially to nutrient cycling in the oceans and can engage in close interactions with microalgae. Many microalgae harbor characteristic satellite bacteria, many of which participate in N-acyl homoserine lactone (AHL) ... ...

    Abstract Marine bacteria contribute substantially to nutrient cycling in the oceans and can engage in close interactions with microalgae. Many microalgae harbor characteristic satellite bacteria, many of which participate in N-acyl homoserine lactone (AHL) mediated quorum sensing. In the diffusion-controlled phycosphere, AHLs can reach high local concentrations, with some of them transforming into tetramic acids, compounds with a broad bioactivity. We tested a representative AHL, N-(3-oxododecanoyl) homoserine lactone, and its tetramic acid rearrangement product on the diatom Phaeodactylum tricornutum. While cell growth and photosynthetic efficiency of photosystem II were barely affected by the AHL, exposure to its tetramic acid rearrangement product had a negative effect on photosynthetic efficiency and led to growth inhibition and cell death in the long term, with a minimum inhibitory concentration between 20 and 50 μΜ. These results strengthen the view that AHLs may play an important role in shaping the outcome of microalgae-bacteria interactions.
    MeSH term(s) 4-Butyrolactone/analogs & derivatives ; 4-Butyrolactone/chemistry ; 4-Butyrolactone/pharmacology ; Diatoms/drug effects ; Diatoms/growth & development ; Diatoms/physiology ; Photosynthesis/drug effects ; Pyrrolidinones/pharmacology
    Chemical Substances Pyrrolidinones ; homoserine lactone (1192-20-7) ; tetramic acid (503-83-3) ; 4-Butyrolactone (OL659KIY4X)
    Language English
    Publishing date 2019-02-06
    Publishing country United States
    Document type Letter ; Research Support, Non-U.S. Gov't
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.8b01101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Senna alata.

    Hennebelle, Thierry / Weniger, Bernard / Joseph, Henry / Sahpaz, Sevser / Bailleul, François

    Fitoterapia

    2009  Volume 80, Issue 7, Page(s) 385–393

    Abstract: A review is made of chemical, ethnopharmacological and pharmacological papers dealing with Senna alata (L.) Roxb., a plant that belongs to the Creole traditional system of medicine and that has recently been introduced in the French Pharmacopoeia. The ... ...

    Abstract A review is made of chemical, ethnopharmacological and pharmacological papers dealing with Senna alata (L.) Roxb., a plant that belongs to the Creole traditional system of medicine and that has recently been introduced in the French Pharmacopoeia. The proofs existing for its various usages are presented. The species is mainly used against constipation and skin diseases. The laxative activity is supported by scientific findings. In contrast the dermatologic use requires further investigation. The species can be considered as safe for short-term or topical use.
    MeSH term(s) Animals ; Constipation/drug therapy ; Ethnopharmacology ; France ; Laxatives/pharmacology ; Laxatives/therapeutic use ; Mice ; Pharmacopoeias as Topic ; Phytotherapy ; Rats ; Senna Extract/adverse effects ; Senna Extract/pharmacology ; Senna Extract/therapeutic use ; Senna Plant/chemistry ; Skin Diseases/drug therapy
    Chemical Substances Laxatives ; Senna Extract (8013-11-4)
    Language English
    Publishing date 2009-10
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 412385-2
    ISSN 1873-6971 ; 0367-326X
    ISSN (online) 1873-6971
    ISSN 0367-326X
    DOI 10.1016/j.fitote.2009.05.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Prognostic impact of prepercutaneous coronary intervention TIMI flow in patients with ST-segment and non-ST-segment elevation myocardial infarction: Results from the FAST-MI 2010 registry.

    Bailleul, Clotilde / Aissaoui, Nadia / Cayla, Guillaume / Dillinger, Jean-Guillaume / Jouve, Bernard / Schiele, François / Ferrières, Jean / Simon, Tabassome / Danchin, Nicolas / Puymirat, Etienne

    Archives of cardiovascular diseases

    2017  Volume 111, Issue 2, Page(s) 101–108

    Abstract: Background: Thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3 before percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is associated with improved outcomes. However, no recent data are available on its impact ... ...

    Abstract Background: Thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3 before percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is associated with improved outcomes. However, no recent data are available on its impact beyond 1 year and/or by type of AMI.
    Aims: To assess the prognostic impact of prePCI TIMI flow at 30 days and 3 years in patients with ST-segment elevation (STEMI) or non-ST-segment elevation (NSTEMI) AMI.
    Methods: We compared long-term outcomes associated with TIMI flow grade 2/3 versus 0/1 in patients referred for PCI in the nationwide French registry of acute ST-segment elevation or non-ST-segment elevation myocardial infarction (FAST-MI) 2010.
    Results: TIMI flow grade 2/3 was found in 41% of patients with STEMI and 69% of patients with NSTEMI; it was associated with a lower risk of 30-day death in patients with STEMI (odds ratio 0.30, 95% confidence interval [CI] 0.12-0.77; P=0.01), but not in patients with NSTEMI (odds ratio 0.57, 95% CI 0.22-1.42; P=0.23). TIMI grade flow 2/3 was also associated with a lower risk of 3-year death in patients with STEMI (hazard ratio 0.69, 95% CI 0.49-0.98; P=0.04), but not in patients with NSTEMI (hazard ratio 0.79, 95% CI 0.56-1.11; P=0.17).
    Conclusion: TIMI flow grade 2/3 is observed more often in patients with NSTEMI; it is an independent predictor of early and late survival in patients with STEMI, but is not significantly related to early or long-term survival in patients with NSTEMI.
    MeSH term(s) Aged ; Blood Flow Velocity ; Chi-Square Distribution ; Coronary Circulation ; Female ; France ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Non-ST Elevated Myocardial Infarction/diagnosis ; Non-ST Elevated Myocardial Infarction/mortality ; Non-ST Elevated Myocardial Infarction/physiopathology ; Non-ST Elevated Myocardial Infarction/therapy ; Odds Ratio ; Percutaneous Coronary Intervention/adverse effects ; Percutaneous Coronary Intervention/mortality ; Registries ; Risk Assessment ; Risk Factors ; ST Elevation Myocardial Infarction/diagnosis ; ST Elevation Myocardial Infarction/mortality ; ST Elevation Myocardial Infarction/physiopathology ; ST Elevation Myocardial Infarction/therapy ; Time Factors ; Treatment Outcome
    Language English
    Publishing date 2017-09-19
    Publishing country Netherlands
    Document type Journal Article ; Multicenter Study ; Observational Study
    ZDB-ID 2408778-6
    ISSN 1875-2128 ; 1875-2136
    ISSN (online) 1875-2128
    ISSN 1875-2136
    DOI 10.1016/j.acvd.2017.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: FTO contributes to hepatic metabolism regulation through regulation of leptin action and STAT3 signalling in liver.

    Bravard, Amélie / Vial, Guillaume / Chauvin, Marie-Agnès / Rouillé, Yves / Bailleul, Bernard / Vidal, Hubert / Rieusset, Jennifer

    Cell communication and signaling : CCS

    2014  Volume 12, Page(s) 4

    Abstract: Background: The fat mass and obesity associated (FTO) gene is related to obesity and type 2 diabetes, but its function is still largely unknown. A link between leptin receptor-signal transducers and activators of transcription 3 (LepR-STAT3) signalling ... ...

    Abstract Background: The fat mass and obesity associated (FTO) gene is related to obesity and type 2 diabetes, but its function is still largely unknown. A link between leptin receptor-signal transducers and activators of transcription 3 (LepR-STAT3) signalling pathway and FTO was recently suggested in the hypothalamus. Because of the presence of FTO in liver and the role of LepR-STAT3 in the control of hepatic metabolism, we investigated both in vitro and in vivo the potential interrelationship between FTO and LepR-STAT3 signalling pathway in liver and the impact of FTO overexpression on leptin action and glucose homeostasis in liver of mice.
    Results: We found that FTO protein expression is regulated by both leptin and IL-6, concomitantly to an induction of STAT3 tyrosine phosphorylation, in leptin receptor (LepRb) expressing HuH7 cells. In addition, FTO overexpression in vitro altered both leptin-induced Y705 and S727 STAT3 phosphorylation, leading to dysregulation of glucose-6-phosphatase (G6P) expression and mitochondrial density, respectively. In vivo, liver specific FTO overexpression in mice induced a reducetion of Y705 phosphorylation of STAT3 in nuclear fraction, associated with reduced SOCS3 and LepR mRNA levels and with an increased G6P expression. Interestingly, FTO overexpression also induced S727 STAT3 phosphorylation in liver mitochondria, resulting in an increase of mitochondria function and density. Altogether, these data indicate that FTO promotes mitochondrial recruitment of STAT3 to the detriment of its nuclear localization, affecting in turn oxidative metabolism and the expression of leptin-targeted genes. Interestingly, these effects were associated in mice with alterations of leptin action and hyperleptinemia, as well as hyperglycemia, hyperinsulinemia and glucose intolerance.
    Conclusions: Altogether, these data point a novel regulatory loop between FTO and leptin-STAT3 signalling pathways in liver cells, and highlight a new role of FTO in the regulation of hepatic leptin action and glucose metabolism.
    MeSH term(s) Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Glucose-6-Phosphate/metabolism ; Humans ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mitochondria, Liver/metabolism ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Mutation ; Oxo-Acid-Lyases/genetics ; Oxo-Acid-Lyases/metabolism ; Protein Transport ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Rats ; Receptors, Leptin/genetics ; Receptors, Leptin/metabolism ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins/genetics ; Suppressor of Cytokine Signaling Proteins/metabolism
    Chemical Substances RNA, Messenger ; Receptors, Leptin ; STAT3 Transcription Factor ; Socs3 protein, mouse ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; leptin receptor, mouse ; Glucose-6-Phosphate (56-73-5) ; Mixed Function Oxygenases (EC 1.-) ; FTO protein, mouse (EC 1.14.11.-) ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO (EC 1.14.11.33) ; Oxo-Acid-Lyases (EC 4.1.3.-)
    Language English
    Publishing date 2014-01-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1478-811X
    ISSN (online) 1478-811X
    DOI 10.1186/1478-811X-12-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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