Search

Your search keyword '"Perino, Alessia"' showing total 218 results
Start Over Author "Perino, Alessia"
218 results on '"Perino, Alessia"'

2. Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis

Author

Li, Hao, Perino, Alessia, Huang, Qingyao, Von Alvensleben, Giacomo V.G., Banaei-Esfahani, Amir, Velazquez-Villegas, Laura A., Gariani, Karim, Korbelius, Melanie, Bou Sleiman, Maroun, Imbach, Jéromine, Sun, Yu, Li, Xiaoxu, Bachmann, Alexis, Goeminne, Ludger J.E., Gallart-Ayala, Hector, Williams, Evan G., Ivanisevic, Julijana, Auwerx, Johan, and Schoonjans, Kristina

Published
2022
Full Text
View/download PDF

5. Asparagine protects pericentral hepatocytes during acute liver injury

Author

Sun, Yu, Demagny, Hadrien, Faure, Adrien, Pontanari, Francesca, Jalil, Antoine, Bresciani, Nadia, Yildiz, Ece, Korbelius, Melanie, Perino, Alessia, and Schoonjans, Kristina

Subjects
Asparagine -- Health aspects, Liver diseases -- Care and treatment -- Patient outcomes, Health care industry
Abstract

The nonessential amino acid asparagine can only be synthesized de novo by the enzymatic activity of asparagine synthetase (ASNS). While ASNS and asparagine have been implicated in the response to numerous metabolic stressors in cultured cells, the in vivo relevance of this enzyme in stress-related pathways remains unexplored. Here, we found ASNS to be expressed in pericentral hepatocytes, a population of hepatic cells specialized in xenobiotic detoxification. ASNS expression was strongly enhanced in 2 models of acute liver injury: carbon tetrachloride (C[Cl.sub.4]) and acetaminophen. We found that mice with hepatocyte-specific Asns deletion were more prone to pericentral liver damage than their control littermates after toxin exposure. This phenotype could be reverted by i.v. administration of asparagine. Unexpectedly, the stress- induced upregulation of ASNS involved an ATF4-independent, noncanonical pathway mediated by the nuclear receptor, liver receptor homolog 1 (LRH-1; NR5A2). Altogether, our data indicate that the induction of the asparagine-producing enzyme ASNS acts as an adaptive mechanism to constrain the necrotic wave that follows toxin administration and provide proof of concept that i.v. delivery of asparagine can dampen hepatotoxin-induced pericentral hepatocellular death., Introduction The liver is a highly structured tissue where oxygen-rich blood enters the hepatic lobule at peripheral portal triads and drains out through the central vein (reviewed in ref. 1). [...]

Published
2023
Full Text
View/download PDF

6. Central anorexigenic actions of bile acids are mediated by TGR5

Author

Perino, Alessia, Velázquez-Villegas, Laura. A., Bresciani, Nadia, Sun, Yu, Huang, Qingyao, Fénelon, Valérie S., Castellanos-Jankiewicz, Ashley, Zizzari, Philippe, Bruschetta, Giuseppe, Jin, Sungho, Baleisyte, Aiste, Gioiello, Antimo, Pellicciari, Roberto, Ivanisevic, Julijana, Schneider, Bernard L., Diano, Sabrina, Cota, Daniela, and Schoonjans, Kristina

Published
2021
Full Text
View/download PDF

9. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance

Author

Fang, Sungsoon, Suh, Jae Myoung, Reilly, Shannon M, Yu, Elizabeth, Osborn, Olivia, Lackey, Denise, Yoshihara, Eiji, Perino, Alessia, Jacinto, Sandra, Lukasheva, Yelizaveta, Atkins, Annette R, Khvat, Alexander, Schnabl, Bernd, Yu, Ruth T, Brenner, David A, Coulter, Sally, Liddle, Christopher, Schoonjans, Kristina, Olefsky, Jerrold M, Saltiel, Alan R, Downes, Michael, and Evans, Ronald M

Subjects
Biomedical and Clinical Sciences, Health Sciences, Adipose Tissue, Brown, Adipose Tissue, White, Animals, Benzene Derivatives, Bile Acids and Salts, Fibroblast Growth Factors, Glucose Clamp Technique, Insulin Resistance, Intestinal Mucosa, Mice, Obesity, Receptors, Cytoplasmic and Nuclear, Weight Gain, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile acid release during a meal selectively activates intestinal FXR. By mimicking this tissue-selective effect, the gut-restricted FXR agonist fexaramine (Fex) robustly induces enteric fibroblast growth factor 15 (FGF15), leading to alterations in BA composition, but does so without activating FXR target genes in the liver. However, unlike systemic agonism, we find that Fex reduces diet-induced weight gain, body-wide inflammation and hepatic glucose production, while enhancing thermogenesis and browning of white adipose tissue (WAT). These pronounced metabolic improvements suggest tissue-restricted FXR activation as a new approach in the treatment of obesity and metabolic syndrome.

Published
2015

11. Genetic and dietary modulators of the inflammatory response in the gastrointestinal tract of the BXD mouse genetic reference population

Author

Li, Xiaoxu, primary, Morel, Jean-David, additional, Benegiamo, Giorgia, additional, Poisson, Johanne, additional, Bachmann, Alexis, additional, Rapin, Alexis, additional, Sulc, Jonathan, additional, Williams, Evan, additional, Perino, Alessia, additional, Schoonjans, Kristina, additional, Bou Sleiman, Maroun, additional, and Auwerx, Johan, additional

Published
2023
Full Text
View/download PDF

12. Phosphoinositide 3-Kinase &ggr; Protects Against Catecholamine-Induced Ventricular Arrhythmia Through Protein Kinase A–Mediated Regulation of Distinct Phosphodiesterases

Author

Ghigo, Alessandra, Perino, Alessia, Mehel, Hind, Zahradníková, Alexandra, Morello, Fulvio, Leroy, Jérôme, Nikolaev, Viacheslav O, Damilano, Federico, Cimino, James, De Luca, Elisa, Richter, Wito, Westenbroek, Ruth, Catterall, William A, Zhang, Jin, Yan, Chen, Conti, Marco, Gomez, Ana Maria, Vandecasteele, Grégoire, Hirsch, Emilio, and Fischmeister, Rodolphe

Subjects
Heart Disease - Coronary Heart Disease, Cardiovascular, Heart Disease, 2.1 Biological and endogenous factors, Aetiology, Animals, Animals, Newborn, Biofeedback, Psychology, Calcium Signaling, Catecholamines, Class Ib Phosphatidylinositol 3-Kinase, Cyclic AMP-Dependent Protein Kinases, Cyclic Nucleotide Phosphodiesterases, Type 3, Cyclic Nucleotide Phosphodiesterases, Type 4, Gene Knock-In Techniques, Isoenzymes, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Myocytes, Cardiac, Tachycardia, Ventricular, arrhythmias, cardiac, class II phosphatidylinositol 3-kinases, ', 5 '-cyclic-AMP phosphodiesterases, cyclic AMP-dependent protein kinases, receptors, adrenergic beta-2, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BackgroundPhosphoinositide 3-kinase γ (PI3Kγ) signaling engaged by β-adrenergic receptors is pivotal in the regulation of myocardial contractility and remodeling. However, the role of PI3Kγ in catecholamine-induced arrhythmia is currently unknown.Methods and resultsMice lacking PI3Kγ (PI3Kγ(-/-)) showed runs of premature ventricular contractions on adrenergic stimulation that could be rescued by a selective β(2)-adrenergic receptor blocker and developed sustained ventricular tachycardia after transverse aortic constriction. Consistently, fluorescence resonance energy transfer probes revealed abnormal cAMP accumulation after β(2)-adrenergic receptor activation in PI3Kγ(-/-) cardiomyocytes that depended on the loss of the scaffold but not of the catalytic activity of PI3Kγ. Downstream from β-adrenergic receptors, PI3Kγ was found to participate in multiprotein complexes linking protein kinase A to the activation of phosphodiesterase (PDE) 3A, PDE4A, and PDE4B but not of PDE4D. These PI3Kγ-regulated PDEs lowered cAMP and limited protein kinase A-mediated phosphorylation of L-type calcium channel (Ca(v)1.2) and phospholamban. In PI3Kγ(-/-) cardiomyocytes, Ca(v)1.2 and phospholamban were hyperphosphorylated, leading to increased Ca(2+) spark occurrence and amplitude on adrenergic stimulation. Furthermore, PI3Kγ(-/-) cardiomyocytes showed spontaneous Ca(2+) release events and developed arrhythmic calcium transients.ConclusionsPI3Kγ coordinates the coincident signaling of the major cardiac PDE3 and PDE4 isoforms, thus orchestrating a feedback loop that prevents calcium-dependent ventricular arrhythmia.

Published
2012

13. Author Response: Genetic and dietary modulators of the inflammatory response in the gastro-intestinal tract of the BXD mouse genetic reference population

Author

Li, Xiaoxu, primary, Morel, Jean-David, additional, Benegiamo, Giorgia, additional, Poisson, Johanne, additional, Bachmann, Alexis, additional, Rapin, Alexis, additional, Sulc, Jonathan, additional, Williams, Evan, additional, Perino, Alessia, additional, Schoonjans, Kristina, additional, Sleiman, Maroun Bou, additional, and Auwerx, Johan, additional

Published
2023
Full Text
View/download PDF

14. Genetic and dietary modulators of the inflammatory response in the gastro-intestinal tract of the BXD mouse genetic reference population

Author

Li, Xiaoxu, primary, Morel, Jean-David, additional, Benegiamo, Giorgia, additional, Poisson, Johanne, additional, Bachmann, Alexis, additional, Rapin, Alexis, additional, Sulc, Jonathan, additional, Williams, Evan, additional, Perino, Alessia, additional, Schoonjans, Kristina, additional, Sleiman, Maroun Bou, additional, and Auwerx, Johan, additional

Published
2023
Full Text
View/download PDF

16. Role of TGR5 in fat-to-liver communication during NAFLD

Author

Simão, André L., primary, Fernandes, Diogo, additional, Silva, Daniela, additional, Silva, Margarida, additional, Afonso, Marta B., additional, Santos, André A., additional, Henrique, Mariana Moura, additional, Palma, Carolina Santos, additional, Lapitz, Ainhoa, additional, Izquierdo-Sánchez, Laura, additional, Rodrigues, Pedro Miguel, additional, Perino, Alessia, additional, Costa-Silva, Bruno, additional, Rodrigues, Cecília M.P, additional, Cortez-Pinto, Helena, additional, Martínez-Chantar, María Luz, additional, Schoonjans, Kristina, additional, Banales, Jesus Maria, additional, and Castro, Rui E., additional

Published
2023
Full Text
View/download PDF

17. A microbial-derived succinylated bile acid to safeguard liver health.

Author

Perino, Alessia, Demagny, Hadrien, and Schoonjans, Kristina

Subjects
*BILE acids, *CHOLIC acid, *CELLULAR signal transduction, *LIVER diseases, *AUTHORSHIP collaboration
Abstract

In this issue of Cell , Nie and co-authors report that the microbe-derived bile acid (BA) 3-succinylated cholic acid protects against the progression of metabolic dysfunction-associated liver disease. Intriguingly, its protective mechanism does not involve traditional BA signaling pathways but is instead linked to the proliferation of the commensal microbe Akkermansia muciniphila. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

27. Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline Cardiotoxicity and Reduces Tumor Growth

Author

Li, Mingchuan, Sala, Valentina, De Santis, Maria Chiara, Cimino, James, Cappello, Paola, Pianca, Nicola, Di Bona, Anna, Margaria, Jean Piero, Martini, Miriam, Lazzarini, Edoardo, Pirozzi, Flora, Rossi, Luca, Franco, Irene, Bornbaum, Julia, Heger, Jacqueline, Rohrbach, Susanne, Perino, Alessia, Tocchetti, Carlo G., Lima, Braulio H.F., Teixeira, Mauro M., Porporato, Paolo E., Schulz, Rainer, Angelini, Annalisa, Sandri, Marco, Ameri, Pietro, Sciarretta, Sebastiano, Lima-Júnior, Roberto César P., Mongillo, Marco, Zaglia, Tania, Morello, Fulvio, Novelli, Francesco, Hirsch, Emilio, and Ghigo, Alessandra

Published
2018
Full Text
View/download PDF

29. Identification of a Crosstalk among TGR5, GLIS2, and TP53 Signaling Pathways in the Control of Undifferentiated Germ Cell Homeostasis and Chemoresistance

Author

Thirouard, Laura, primary, Holota, Hélène, additional, Monrose, Mélusine, additional, Garcia, Manon, additional, de Haze, Angélique, additional, Damon‐Soubeyrand, Christelle, additional, Renaud, Yoan, additional, Saru, Jean‐Paul, additional, Perino, Alessia, additional, Schoonjans, Kristina, additional, Beaudoin, Claude, additional, and Volle, David H., additional

Published
2022
Full Text
View/download PDF

30. Integrating Cardiac PIP 3 and cAMP Signaling through a PKA Anchoring Function of p110γ

Author

Perino, Alessia, Ghigo, Alessandra, Ferrero, Enrico, Morello, Fulvio, Santulli, Gaetano, Baillie, George S., Damilano, Federico, Dunlop, Allan J., Pawson, Catherine, Walser, Romy, Levi, Renzo, Altruda, Fiorella, Silengo, Lorenzo, Langeberg, Lorene K., Neubauer, Gitte, Heymans, Stephane, Lembo, Giuseppe, Wymann, Matthias P., Wetzker, Reinhard, Houslay, Miles D., Iaccarino, Guido, Scott, John D., and Hirsch, Emilio

Published
2011
Full Text
View/download PDF

32. TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation

Author

Perino, Alessia, Pols, Thijs Willem Hendrik, Nomura, Mitsunori, Stein, Sokrates, Pellicciari, Roberto, and Schoonjans, Kristina

Subjects
Insulin resistance -- Research, Protein kinases -- Physiological aspects -- Research, Macrophages -- Physiological aspects -- Research, Cell receptors -- Physiological aspects -- Research, Health care industry
Abstract

The bile acid-responsive G protein-coupled receptor TGR5 is involved in several metabolic processes, and recent studies suggest that TGR5 activation may promote pathways that are protective against diet-induced diabetes. Here, we investigated the role of macrophage-specific TGR5 signaling in protecting adipose tissue from inflammation and associated insulin resistance. Examination of adipose tissue from obese mice lacking macrophage Tgr5 revealed enhanced inflammation, increased chemokine expression, and higher macrophage numbers compared with control obese animals. Moreover, macrophage-specific deletion of Tgr5 exacerbated insulin resistance in obese animals. Conversely, pharmacological activation of TGR5 markedly decreased LPS-induced chemokine expression in primary macrophages. This reduction was mediated by AKT-dependent activation of mTOR complex 1, which in turn induced the differential translation of the dominant-negative C/EBPβ isoform, liver inhibitory protein (LIP). Overall, these studies reveal a signaling pathway downstream of TGR5 that modulates chemokine expression in response to high-fat diet and suggest that targeting this pathway has the potential to be therapeutically exploited for prevention of chronic inflammatory diseases and type 2 diabetes mellitus., Introduction Type 2 diabetes mellitus (T2DM) is rising in incidence worldwide and constitutes a major public health burden (1). T2DM is characterized by hyperglycemia and is caused by progressive peripheral [...]

Published
2014
Full Text
View/download PDF

33. Eliciting the mitochondrial unfolded protein response by nicotinamide adenine dinucleotide repletion reverses fatty liver disease in mice

Author

Gariani, Karim, Menzies, Keir J., Ryu, Dongryeol, Wegner, Casey J., Wang, Xu, Ropelle, Eduardo R., Moullan, Norman, Zhang, Hongbo, Perino, Alessia, Lemos, Vera, Kim, Bohkyung, Park, Young-Ki, Piersigilli, Alessandra, Pham, Tho X., Yang, Yue, Ku, Chai Siah, Koo, Sung I., Fomitchova, Anna, Cantó, Carlos, Schoonjans, Kristina, Sauve, Anthony A., Lee, Ji-Young, and Auwerx, Johan

Published
2016
Full Text
View/download PDF

35. Hypothalamic bile acid-TGR5 signaling protects from obesity

Author

Castellanos-Jankiewicz, Ashley, Guzmán-Quevedo, Omar, Fénelon, Valérie S., Zizzari, Philippe, Quarta, Carmelo, Bellocchio, Luigi, Tailleux, Anne, Charton, Julie, Fernandois, Daniela, Henricsson, Marcus, Piveteau, Catherine, Simon, Vincent, Allard, Camille, Quemener, Sandrine, Guinot, Valentine, Hennuyer, Nathalie, Perino, Alessia, Duveau, Alexia, Maitre, Marlène, Leste-Lasserre, Thierry, Clark, Samantha, Dupuy, Nathalie, Cannich, Astrid, Gonzales, Delphine, Deprez, Benoit, Mithieux, Gilles, Dombrowicz, David, Bäckhed, Fredrik, Prevot, Vincent, Marsicano, Giovanni, Staels, Bart, Schoonjans, Kristina, and Cota, Daniela

Published
2021
Full Text
View/download PDF

37. Short Article Hypothalamic bile acid-TGR5 signaling protects from obesity

Author

Castellanos-Jankiewicz, Ashley, Guzman-Quevedo, Omar, Fenelon, Valerie S., Zizzari, Philippe, Quarta, Carmelo, Bellocchio, Luigi, Tailleux, Anne, Charton, Julie, Fernandois, Daniela, Henricsson, Marcus, Piveteau, Catherine, Simon, Vincent, Allard, Camille, Quemener, Sandrine, Guinot, Valentine, Hennuyer, Nathalie, Perino, Alessia, Duveau, Alexia, Maitre, Marlene, Leste-Lasserre, Thierry, Clark, Samantha, Dupuy, Nathalie, Cannich, Astrid, Gonzales, Delphine, Deprez, Benoit, Mithieux, Gilles, Dombrowicz, David, Backhed, Fredrik, Prevot, Vincent, Marsicano, Giovanni, Staels, Bart, Schoonjans, Kristina, Cota, Daniela, Castellanos-Jankiewicz, Ashley, Guzman-Quevedo, Omar, Fenelon, Valerie S., Zizzari, Philippe, Quarta, Carmelo, Bellocchio, Luigi, Tailleux, Anne, Charton, Julie, Fernandois, Daniela, Henricsson, Marcus, Piveteau, Catherine, Simon, Vincent, Allard, Camille, Quemener, Sandrine, Guinot, Valentine, Hennuyer, Nathalie, Perino, Alessia, Duveau, Alexia, Maitre, Marlene, Leste-Lasserre, Thierry, Clark, Samantha, Dupuy, Nathalie, Cannich, Astrid, Gonzales, Delphine, Deprez, Benoit, Mithieux, Gilles, Dombrowicz, David, Backhed, Fredrik, Prevot, Vincent, Marsicano, Giovanni, Staels, Bart, Schoonjans, Kristina, and Cota, Daniela

Abstract

Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet induced obesity.

Published
2021

41. WED-397 - Role of TGR5 in fat-to-liver communication during NAFLD

Author

Simão, André L., Fernandes, Diogo, Silva, Daniela, Silva, Margarida, Afonso, Marta B., Santos, André A., Henrique, Mariana Moura, Palma, Carolina Santos, Lapitz, Ainhoa, Izquierdo-Sánchez, Laura, Rodrigues, Pedro Miguel, Perino, Alessia, Costa-Silva, Bruno, Rodrigues, Cecília M.P, Cortez-Pinto, Helena, Martínez-Chantar, María Luz, Schoonjans, Kristina, Banales, Jesus Maria, and Castro, Rui E.

Published
2023
Full Text
View/download PDF

49. Contractile Function during Angiotensin-II Activation:Increased Nox2 Activity Modulates Cardiac Calcium Handling via Phospholamban Phosphorylation

Author

Zhang, Min, Prosser, Benjamin L., Bamboye, Moradeke A., Gondim, Antonio N.S., Santos, Celio X., Martin, Daniel, Ghigo, Alessandra, Perino, Alessia, Brewer, Alison C., Ward, Christopher W., Hirsch, Emilio, Lederer, W. Jonathan, and Shah, Ajay M.

Subjects
NADPH oxidase, angiotensin II, contraction, myocyte, Cardiology and Cardiovascular Medicine, cardiovascular system, hormones, hormone substitutes, and hormone antagonists
Abstract

Background Renin-angiotensin system activation is a feature of many cardiovascular conditions. Activity of myocardial reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NADPH oxidase 2 or Nox2) is enhanced by angiotensin II (Ang II) and contributes to increased hypertrophy, fibrosis, and adverse remodeling. Recent studies found that Nox2-mediated reactive oxygen species production modulates physiological cardiomyocyte function. Objectives This study sought to investigate the effects of cardiomyocyte Nox2 on contractile function during increased Ang II activation. Methods We generated a cardiomyocyte-targeted Nox2-transgenic mouse model and studied the effects of in vivo and ex vivo Ang II stimulation, as well as chronic aortic banding. Results Chronic subpressor Ang II infusion induced greater cardiac hypertrophy in transgenic than wild-type mice but unexpectedly enhanced contractile function. Acute Ang II treatment also enhanced contractile function in transgenic hearts in vivo and transgenic cardiomyocytes ex vivo. Ang II-stimulated Nox2 activity increased sarcoplasmic reticulum (SR) Ca2+ uptake in transgenic mice, increased the Ca2+ transient and contractile amplitude, and accelerated cardiomyocyte contraction and relaxation. Elevated Nox2 activity increased phospholamban phosphorylation in both hearts and cardiomyocytes, related to inhibition of protein phosphatase 1 activity. In a model of aortic banding-induced chronic pressure overload, heart function was similarly depressed in transgenic and wild-type mice. Conclusions We identified a novel mechanism in which Nox2 modulates cardiomyocyte SR Ca2+ uptake and contractile function through redox-regulated changes in phospholamban phosphorylation. This mechanism can drive increased contractility in the short term in disease states characterized by enhanced renin-angiotensin system activation.

Published
2015
Full Text
View/download PDF

50. PI3K-C2γ 3 is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling

Author

Braccini, Laura, Ciraolo, Elisa, Campa, CARLO COSIMO, Perino, Alessia, Longo, DARIO LIVIO, Tibolla, Gianpaolo, Pregnolato, Marco, Cao, Yanyan, Tassone, Beatrice, Damilano, Federico, Laffargue, Muriel, Calautti, Vincenzo, Falasca, Marco, Norata, Giuseppe D., Backer, Jonathan M., and Hirsch, Emilio

Subjects
Genetics and Molecular Biology (all), Physics and Astronomy (all), Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Biochemistry
Published
2015

Catalog

Books, media, physical & digital resources
See catalog results